1272:, called LanB enzymes, though more specific designations are used for particular lanthipeptides (e.g. NisB is the nisin dehydratase). A separate cyclase, LanC, is responsible for the second step in Lan and MeLan biosynthesis. However, class II, III, and IV lanthipeptides have bifunctional lanthionine synthetases in their gene clusters, meaning a single enzyme carries out both dehydration and cyclization steps. Class II synthetases, designated LanM synthetases, have N-terminal dehydration domains with no sequence homology to other lanthipeptide biosynthetic enzymes; the cyclase domain has homology to LanC. Class III (LanKC) and IV (LanL) enzymes have similar N-terminal
1090:
1241:
1564:
759:
identified by molecular weight, native producer, and antibacterial activity. Microcins are either plasmid- or chromosome-encoded, but specifically have activity against
Enerobacteriaceae. Because these organisms are also often producers of microcins, the gene cluster contains not only a precursor peptide and modification enzymes, but also a self-immunity gene to protect the producing strain, and genes encoding export of the natural product.
1714:
Jaspars M, Kelly WL, Klinman JP, Kuipers OP, Link AJ, Liu W, Marahiel MA, Mitchell DA, Moll GN, Moore BS, Müller R, Nair SK, Nes IF, Norris GE, Olivera BM, Onaka H, Patchett ML, Piel J, Reaney MJ, Rebuffat S, Ross RP, Sahl HG, Schmidt EW, Selsted ME, Severinov K, Shen B, Sivonen K, Smith L, Stein T, Süssmuth RD, Tagg JR, Tang GL, Truman AW, Vederas JC, Walsh CT, Walton JD, Wenzel SC, Willey JM, van der Donk WA (January 2013).
887:, although this term is used more broadly. The distinctive nature of this class is not only the relatively large size of the natural products but also the modifying enzymes responsible for macrocyclization. Other N-to-C cyclized RiPPs, such as the cyanobactins and orbitides, have specialized biosynthetic machinery for macrocylization of much smaller core peptides. Thus far, these bacteriocins have been identified only in
691:
1289:
779:
568:(Lan) and 3-methyllanthionine (MeLan) residues in the final natural product. There are four major classes of lanthipeptides, delineated by the enzymes responsible for installation of Lan and MeLan. The dehydratase and cyclase can be two separate proteins or one multifunctional enzyme. Previously, lanthipeptides were known as "lantipeptides" before a consensus was reached in the field.
522:
480:
554:
436:
22:
1713:
Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD, Craik DJ, Dawson M, Dittmann E, Donadio S, Dorrestein PC, Entian KD, Fischbach MA, Garavelli JS, Göransson U, Gruber CW, Haft DH, Hemscheidt TK, Hertweck C, Hill C, Horswill AR,
971:
are characterized by C-terminal aminovinyl cysteine residues. While this posttranslational modification is also seen in the lanthipeptides epidermin and mersacidin, linaridins do not have Lan or MeLan residues. In addition, the linaridin moiety is formed from modification of two Cys residues, whereas
940:
motif. No other posttranslational modifications have been observed on the characterized cyclotides, which are between 28 - 37 amino acids in size. Cyclotides are plant natural products and the different cyclotides appear to be species-specific. While many activities have been reported for cyclotides,
1387:
For cyanobactins, the precursor peptide is referred to as the E peptide. Minimally, the E peptide requires a leader peptide region, a core (structural) region, and both N-terminal and C-terminal protease recognition sequences. In contrast to most RiPPs, for which a single precursor peptide encodes a
540:
The precursor peptide of the cyanobactin family is traditionally designated the "E" gene, whereas precursor peptides are designated gene "A" in most RiPP gene clusters. "A" is a serine protease involved in cleavage of the leader peptide and subsequent macrocyclization of the peptide natural product,
1567:(A) Representative examples of lasso peptide biosynthetic gene clusters. Arrows depicting open reading frames are shown with lengths proportional to gene size, as indicated by the scale bar. Genes are color coded and labeled according to function. (B) General scheme of lasso peptide biosynthesis.
996:
are plant-derived N-to-C cyclized peptides with no disulfide bonds. Also referred to as
Caryophyllaceae-like homomonocyclopeptides, orbitides are 5-12 amino acids in length and are composed of mainly hydrophobic residues. Similar to the amatoxins and phallotoxins, the gene sequences of orbitides
536:
with N-to-C macrocylization of a 6–20 amino acid chain. Cyanobactins are natural products isolated from cyanobacteria, and close to 30% of all cyanobacterial strains are thought to contain cyanobacterial gene clusters. However, while thus far all cyanobactins are credited to cyanobacteria, there
901:
and, like other bacteriocins, is relatively resistant to high temperature, pH changes, and many proteases as a result of macrocyclization. Based on solution structures and sequence alignments, bacteriocins appear to take on similar 3D structures despite little sequence homology, contributing to
454:
are 8- and 7-membered natural products, respectively, characterized by N-to-C cyclization in addition to a tryptathionine motif derived from the crosslinking of Cys and Trp. The amatoxins and phallotoxins also differ from other RiPPs based on the presence of a C-terminal recognition sequence in
3334:
Kawulka KE, Sprules T, Diaper CM, Whittal RM, McKay RT, Mercier P, Zuber P, Vederas JC (2004). "Structure of subtilosin A, a cyclic antimicrobial peptide from
Bacillus subtilis with unusual sulfur to alpha-carbon cross-links: formation and reduction of alpha-thio-alpha-amino acid derivatives".
830:. Perhaps the most well-characterized thiopeptide, thiostrepton A, contains a dehydropiperidine ring and a second, quinaldic acid-containing macrocycle. Four residues are dehydrated during posttranslational modification, and the final natural product also bears four thiazoles and one azoline.
758:
with a molecular weight <10 kDa. Many members of other RiPP families, such as microcin E492, microcin B17 (LAP) and microcin J25 (Lasso peptide) are also considered microcins. Instead of being classified based on posttranslational modifications or modifying enzymes, microcins are instead
817:
The thiopeptide macrocycle is closed with a six-membered nitrogen-bearing ring. Oxidation state and substitution pattern of the nitrogenous ring determines the series of the thiopeptide natural product. While the mechanism of macrocyclization is not known, the nitrogenous ring can exist in
1257:(Lan) and 3-methyllanthionine (MeLan) residues. Lan residues are formed from a thioether bridge between Cys and Ser, while MeLan residues are formed from the linkage of Cys to a Thr residue. The biosynthetic enzymes responsible for Lan and MeLan installation first dehydrate Ser and Thr to
541:
in combination with an additional serine protease homologue, the encoded by gene "G". Members of the cyanobactin family may bear thiazolines/oxazolines, thiazoles/oxazoles, and methylations depending on additional modification enzymes. For example, perhaps the most famous cyanobactin is
503:
There are currently six known bottromycin compounds, which differ in the extent of side chain methylation, an additional characteristic of the bottromycin class. The total synthesis of bottromycin A2 was required to definitively determine the structure of the first bottromycin.
3370:
Kawulka K, Sprules T, McKay RT, Mercier P, Diaper CM, Zuber P, Vederas JC (2003). "Structure of subtilosin A, an antimicrobial peptide from
Bacillus subtilis with unusual posttranslational modifications linking cysteine sulfurs to alpha-carbons of phenylalanine and threonine".
1019:. However, a metagenomic study revealed the natural products as the most extensively modified class of RiPPs known to date. Six enzymes are responsible for installing a total of 48 posttranslational modifications onto the polytheonamide A and B precursor peptides, including 18
964:
are both Cys-glycosylated and, in addition, have disulfide bonds between non-glycosylated Cys residues. While both members bear S-glycosyl groups, RiPPs bearing O- or N-linked carbohydrates will also be included in this family as they are discovered.
113:
and the accompanying rise in available genomic data, scientific interest in RiPPs has increased in the last few decades. Because the chemical structures of RiPPs are more closely predictable from genomic data than are other natural products (e.g.
740:
S (SLS) is perhaps the most well-studied and most famous LAP, in part because the structure is still unknown since the discovery of SLS in 1901. Thus, while the biosynthetic gene cluster suggests SLS is a LAP, structural confirmation is lacking.
513:. Bottromycins differ from other RiPPs in that there is no N-terminal leader peptide. Rather, the precursor peptide has a C-terminal extension of 35-37 amino acids, hypothesized to act as a recognition sequence for posttranslational machinery.
1571:
Lasso peptide biosynthesis requires at least three genes, referred to as the A, B, and C proteins. The A gene encodes the precursor peptide, which is modified by the B and C proteins into the mature natural product. The B protein is an
717:
forms. Thiazol(in)es are the result of cyclization of Cys residues in the precursor peptide, while (methyl)oxazol(in)es are formed from Thr and Ser. Azole and azoline formation also modifies the residue in the -1 position, or directly
3786:
Morris RP, Leeds JA, Naegeli HU, Oberer L, Memmert K, Weber E, LaMarche MJ, Parker CN, Burrer N, Esterow S, Hein AE, Schmitt EK, Krastel P (2009). "Ribosomally synthesized thiopeptide antibiotics targeting elongation factor Tu".
1482:
The standard nomenclature for thiopeptide biosynthetic proteins follows that of the thiomuracin gene cluster. In addition to the precursor peptide, referred to as the A peptide, thiopeptide biosynthesis requires at least six
1361:, although the D protein alone performs the cyclodehydration reaction. Early work on microcin B17 adopted a different nomenclature for these proteins, but a recent consensus has been adopted by the field as described above.
2240:
990:-acetylated trideca- and tetradecapeptides with ω-ester and/or ω-amide bonds. Lactone formation through glutamate or aspartate ω-carboxy groups and the lysine ε-amino group forms macrocycles in the final natural product.
871:, AIPs are biosynthesized from a precursor peptide composed of a C-terminal leader region, the core region, and negatively charged tail region that is, along with the leader peptide, cleaved before AIP export.
3255:
Hamada T, Matsunaga S, Fujiwara M, Fujita K, Hirota H, Schmucki R, Güntert P, Fusetani N (2010). "Solution structure of polytheonamide B, a highly cytotoxic nonribosomal polypeptide from marine sponge".
1608:
bond. The exact steps and reaction intermediates in lasso peptide biosynthesis remain unknown due to experimental difficulties associated with the proteins. Commonly, the B protein is referred to as the
1534:
is biochemically similar to that of cyanobactins, lanthipeptides, and linear azol(in)e-containing peptides (LAPs). As with cyanobactins and LAPs, azole and azoline synthesis occurs via the action of an
459:, an amatoxin, has a number of posttranslational modifications in addition to macrocyclization and formation of the tryptathionine bridge: oxidation of the tryptathionine leads to the presence of a
1463:
Thiopeptide biosynthesis involves particularly extensive modification of the core peptide scaffold. Indeed, due to the highly complex structures of thiopeptides, it was commonly thought that these
2155:
Gomez-Escribano JP, Song L, Bibb MJ, Challis GL (2012). "Posttranslational β-methylation and macrolactamidination in the biosynthesis of the bottromycin complex of ribosomal peptide antibiotics".
1007:
are named after "Proteus", a Greek shape-shifting sea god. Until now, the only known members in the family of
Proteusins are called polytheonamides. They were originally presumed to be
1117:
long. The leader peptide is usually important for enabling enzymatic processing of the precursor peptide via aiding in recognition of the core peptide by biosynthetic enzymes and for
1620:
Some lasso peptide biosynthetic gene clusters also require an additional protein of unknown function for biosynthesis. Additionally, lasso peptide gene clusters usually include an
1326:
The C protein is mainly involved in leader peptide recognition and binding and is sometimes called a scaffolding protein. The D protein is an ATP-dependent cyclodehydratase that
1081:
RiPPs are characterized by a common biosynthetic strategy wherein genetically-encoded peptides undergo translation and subsequent chemical modification by biosynthetic enzymes.
2824:
Saether O, Craik DJ, Campbell ID, Sletten K, Juul J, Norman DG (1995). "Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1".
1057:, resulting in a circular structure that is conformationally restricted by the Cα bonds. Sactipeptides with antimicrobial activity are commonly referred to as sactibiotics (
161:
guidelines were agreed upon and published by a large group of researchers in the field. Prior to this report, RiPPs were referred to by a variety of designations, including
1418:
that behaves biochemically in the same manner as YcaO-domain cyclodehydratases in thiopeptide and linear azol(in)e-containing peptide (LAP) biosynthesis (described above).
3291:
Iwamoto M, Shimizu H, Muramatsu I, Oiki S (2010). "A cytotoxic peptide from a marine sponge exhibits ion channel activity through vectorial-insertion into the membrane".
1547:
cyclodehydratase. In contrast to LAPs, where cyclodehydration occurs via the action of two distinct proteins responsible for leader peptide binding and cyclodehydrative
40:
736:
is a LAP with extensive cyclization. Two sets of five heterocycles endow the natural product with structural rigidity and unusually selective antibacterial activity.
2789:
Craik DJ, Daly NL, Bond T, Waine C (1999). "Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif".
674:
due to bulky residues on the tail (class II lasso peptides), or both (class III lasso peptides). The compact structure makes lasso peptides frequently resistant to
2023:
Wieland T, Faulstich H (December 1978). "Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous
Amanita mushrooms".
122:), their presence in sequenced organisms can, in theory, be identified rapidly. This makes RiPPs an attractive target of modern natural product discovery efforts.
1551:, these are fused into a single protein (G protein) in cyanobactin and thiopeptide biosynthesis. However, in thiopeptides, an additional protein, designated the
1280:
domains, but diverge in C-terminal cyclization domains: the LanL cyclase domain is homologous to LanC, but the class III enzymes lack Zn-ligand binding domains.
153:
varied accordingly in the literature. More recently, with the advent of broad genome sequencing, it has been realized that these natural products share a common
1053:, the Cα crosslinks between Cys4 and Phe31, Cys7 and Thr28, and Cys13 and Phe22 are not the only posttranslational modifications; the C- and N-termini form an
2120:
Shimamura H, Gouda H, Nagai K, et al. (2009). "Structure determination and total synthesis of bottromycin A2: a potent antibiotic against MRSA and VRE".
1369:
Cyanobactin biosynthesis requires proteolytic cleavage of both N-terminal and C-terminal portions of the precursor peptide. The defining proteins are thus an
1244:(A) Steps in the installation of lanthionine and 3-methyllanthionine bridges in lanthipeptide biosynthesis (B) Classes of lanthipeptide biosynthetic enzymes
1814:"Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments"
1338:
ATP consumption. The C and D proteins are occasionally present as a single, fused protein, as is the case for trunkamide biosynthesis. The B protein is a
651:-based approaches to lasso peptide discovery have thus used this as a constraint. However, some lasso peptides were recently discovered that also contain
920:. Venom peptides from cone snails are generally smaller than those found in other animal venoms (10-30 amino acids vs. 30-90 amino acids) and have more
1392:
via a lone core peptide, cyanobactin E peptides can contain multiple core regions; multiple E peptides can even be present in a single gene cluster.
694:
The structure of plantazolicin, a linear azoli(in)e-containing peptide natural product. Posttranslationally installed azol(in)es are shown in red.
2400:"Characterization of caulonodin lasso peptides revealed unprecedented N-terminal residues and a precursor motif essential for peptide maturation"
1001:, a precursor peptide was found using Blast searching that potentially contains five core peptides separated by putative recognition sequences.
1716:"Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature"
2433:"Structure determination and interception of biosynthetic intermediates for the plantazolicin class of highly discriminating antibiotics"
1855:"Multicenter, randomized clinical trial to compare the safety and efficacy of LFF571 and vancomycin for Clostridium difficile infections"
331:
142:. This combination of peptide translation and modification is referred to as "post-ribosomal peptide synthesis" (PRPS) in analogy with
58:
3873:"Chemoenzymatic synthesis of thiazolyl peptide natural products featuring an enzyme-catalyzed formal [4 + 2] cycloaddition"
1451:; these can occur adjacent to azole or azoline residues. The functions of some proteins found commonly in cyanobactin biosynthetic
1527:
of dehydroalanine moieties to form the characteristic macrocycle. The F protein is responsible for binding of the leader peptide.
1621:
1330:
the cyclodehydration reaction, resulting in formation of an azoline ring. This occurs by direct activation of the amide backbone
545:, which contains two thiazoles, a methyloxazoline, and an oxazoline in its final state, a macrocycle derived from 8 amino acids.
3010:"Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides"
139:
826:. Additionally, some thiopeptides bear a second macrocycle, which bears a quinaldic acid or indolic acid residue derived from
3824:"Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications"
1268:
Four classes of lanthipeptide biosynthetic enzymes have been designated. Class I lanthipeptides have dedicated lanthipeptide
362:, was terminated early as the results were unfavorable. Also recently in clinical trials was the NVB302 (a derivative of the
3925:"Identification of an Auxiliary Leader Peptide-Binding Protein Required for Azoline Formation in Ribosomal Natural Products"
439:
The structure of α-amanitin, with posttranslational modifications particular to the amatoxins and phallotoxins shown in red.
2363:
Maksimov MO, Pan SJ, James Link A (September 2012). "Lasso peptides: structure, function, biosynthesis, and engineering".
1016:
354:
1041:
bear the same modification. In 2003, the first RiPP with a sulfur-to-α-carbon linkage was reported when the structure of
924:. A single species may have 50-200 conopeptides encoded in its genome, recognizable by a well-conserved signal sequence.
1903:"Safety and Efficacy of Multiple Daily Dosing of Oral LFF571 in Patients With Moderate Clostridium Difficile Infections"
557:
The structure of nisin, a lanthipeptide natural product. Lan and MeLan posttranslational modifications are shown in red.
2482:"Structure of the mannose phosphotransferase system (man-PTS) complexed with microcin E492, a pore-forming bacteriocin"
1144:) is recognized and chemically modified sequentially by biosynthetic enzymes (PRPS). Examples of modifications include
349:
1323:
referred to as the B, C, and D proteins; the precursor peptide is referred to as the A protein, as in other classes.
3983:
941:
it has been hypothesized that all are united by a common mechanism of binding to and disrupting the cell membrane.
767:
225:
2861:"The biological activity of the prototypic cyclotide kalata b1 is modulated by the formation of multimeric pores"
1853:
Mullane K, Lee C, Bressler A, Buitrago M, Weiss K, Dabovic K, Praestgaard J, Leeds JA, Blais J, Pertel P (2015).
1600:. The N-terminal amine formed by the B protein (protease) then reacts with this activated side chain to form the
1635:
The biosynthesis of lasso peptides is particularly interesting due to the inaccessibility of the threaded-lasso
1576:-dependent cysteine protease that cleaves the leader region from the precursor peptide. The C protein displays
1555:(F protein) is necessary for leader peptide recognition and potentially recruiting other biosynthetic enzymes.
1023:. Polytheonamides are exceptionally large, as a single molecule is able to span a cell membrane and form an
574:
are lanthipeptides that have known antimicrobial activity. The founding member of the lanthipeptide family,
1089:
3442:
2184:"Widespread occurrence and lateral transfer of the cyanobactin biosynthesis gene cluster in cyanobacteria"
1573:
1536:
1408:
953:
888:
602:
410:
341:
1902:
1407:
moieties from Ser/Thr/Cys residues prior to the action of the A and G proteases. The heterocyclase is an
3978:
1628:, although these are not strictly required for lasso peptide biosynthesis and are sometimes absent. No
1581:
1339:
1300:
867:
3689:
Kelly WL, Pan L, Li C (2009). "Thiostrepton biosynthesis: prototype for a new family of bacteriocins".
3726:"Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin"
3144:
2623:"Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis"
1153:
578:, is a lantibiotic that has been used to prevent the growth of food-born pathogens for over 40 years.
3737:
3211:
3198:
Freeman MF, Gurgui C, Helf MJ, Morinaka BI, Uria AR, Oldham NJ, Sahl HG, Matsunaga S, Piel J (2012).
3021:
2195:
2071:
1652:
1468:
1134:
1118:
1038:
1008:
296:
213:
143:
3067:
Komiyama K, Otoguro K, Segawa T, Shiomi K, Yang H, Takahashi Y, Hayashi M, Otani T, Omura S (1993).
2241:"Biosynthesis, immunity, regulation, mode of action and engineering of the model lantibiotic nisin"
2060:"Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution"
1452:
1114:
564:
are one of the most well-studied families of RiPPs. The family is characterized by the presence of
378:
289:
270:
103:
1949:"Perspectives on lantibiotic discovery - where have we failed and what improvements are required?"
1261:(Dha) and dehydrobutyrine (Dhb), respectively. Subsequent thioether crosslinking occurs through a
1184:
Papers published prior to a recent community consensus employ differing sets of nomenclature. The
770:
activity due to hijacking of specific receptors involved in the transport of essential nutrients.
483:
Structure of
Bottromycin A2 with characteristic posttranslational modifications highlighted in red
149:
Historically, the current sub-classes of RiPPs were studied individually, and common practices in
3473:
3316:
3237:
2771:
2711:
2672:
Sánchez-Hidalgo M, Montalbán-López M, Cebrián R, Valdivia E, Martínez-Bueno M, Maqueda M (2011).
2338:
2278:
755:
292:
1988:
Zanotti G, Beijer B, Wieland T (September 1987). "Synthesis of cyclic tryptathionine peptides".
3493:"Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights"
3406:
Knerr PJ, van der Donk WA (2012). "Discovery, biosynthesis, and engineering of lantipeptides".
3069:"A new antibiotic, cypemycin. Taxonomy, fermentation, isolation and biological characteristics"
3993:
3954:
3902:
3853:
3804:
3765:
3706:
3671:
3622:
3573:
3524:
3465:
3423:
3388:
3352:
3308:
3273:
3229:
3200:"Metagenome mining reveals polytheonamides as posttranslationally modified ribosomal peptides"
3180:
3125:
3090:
3049:
2990:
2941:
2892:
2841:
2806:
2763:
2703:
2654:
2603:
2554:
2519:
2501:
2462:
2431:
Molohon KJ, Melby JO, Lee J, Evans BS, Dunbar KL, Bumpus SB, Kelleher NL, Mitchell DA (2011).
2380:
2330:
2270:
2221:
2137:
2099:
2040:
2005:
1970:
1884:
1835:
1794:
1745:
1640:
1629:
1577:
1431:
1415:
1050:
862:
468:
235:
of RiPPs a common strategy. In part due to their increased discovery and hypothesized ease of
217:
110:
3988:
3944:
3936:
3892:
3884:
3843:
3835:
3796:
3755:
3745:
3698:
3661:
3653:
3612:
3604:
3563:
3555:
3514:
3504:
3457:
3415:
3380:
3344:
3300:
3265:
3219:
3170:
3160:
3143:
Venglat P, Xiang D, Qiu S, Stone SL, Tibiche C, Cram D, Alting-Mees M, Nowak J, Cloutier S,
3117:
3080:
3039:
3029:
2980:
2972:
2931:
2923:
2882:
2872:
2833:
2798:
2753:
2745:
2693:
2685:
2644:
2634:
2593:
2585:
2546:
2509:
2493:
2452:
2444:
2411:
2372:
2320:
2260:
2252:
2211:
2203:
2164:
2129:
2089:
2079:
2032:
1997:
1960:
1874:
1866:
1825:
1784:
1776:
1735:
1727:
1563:
1464:
1262:
1164:(i.e. lasso peptides), among others. The resulting modified precursor peptide (containing a
1046:
507:
Thus far, gene clusters predicted to produce bottromycins have been identified in the genus
405:
382:
334:
259:
201:
135:
1479:
came in 2009 with the independent discovery of the gene clusters for several thiopeptides.
1296:
The hallmark of linear azol(in)e-containing peptide (LAP) biosynthesis is the formation of
1240:
593:"ring" through which a linear C-terminal "tail" is threaded. Because of this threaded-loop
3419:
1585:
1389:
933:
679:
415:
371:
345:
251:
1172:, wherein the non-core regions of the precursor peptide are removed. This results in the
3741:
3544:"Thiazole/oxazole-modified microcins: complex natural products from ribosomal templates"
3215:
3025:
2758:
2733:
2698:
2673:
2265:
2199:
2075:
3949:
3924:
3897:
3872:
3848:
3823:
3760:
3725:
3666:
3641:
3617:
3592:
3568:
3543:
3519:
3492:
3175:
3148:
3044:
3009:
2985:
2960:
2936:
2911:
2887:
2860:
2649:
2622:
2598:
2573:
2514:
2481:
2457:
2432:
2216:
2183:
2001:
1879:
1854:
1789:
1764:
1740:
1715:
1544:
1494:
1440:
1335:
1258:
973:
921:
846:
842:
671:
648:
303:
263:
2094:
2059:
3972:
1524:
1503:
1448:
1020:
937:
763:
733:
723:
542:
533:
464:
456:
419:
397:
390:
221:
3320:
3241:
2775:
2715:
2342:
537:
exists the possibility that other organisms could produce similar natural products.
3839:
3822:
Liao R, Duan L, Lei C, Pan H, Ding Y, Zhang Q, Chen D, Shen B, Yu Y, Liu W (2009).
3657:
3642:"Linking chemistry and genetics in the growing cyanobactin natural products family"
3593:"YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations"
3477:
2282:
1625:
1531:
1149:
1012:
997:
suggest the presence of a C-terminal recognition sequence. In the flaxseed variety
950:
897:
883:
878:
850:
790:
have been isolated from
Actinobacteria. General structural features of thiopeptide
737:
727:
571:
509:
450:
401:
327:
285:
281:
158:
154:
150:
86:
origin. Consisting of more than 20 sub-classes, RiPPs are produced by a variety of
3304:
1965:
1948:
956:. Only two members have been fully characterized, making this a small RiPP class.
690:
3509:
2480:
Huang, Kai; Zeng, Jianwei; Liu, Xueli; Jiang, Tianyu; Wang, Jiawei (2021-04-06).
1292:
Schematic representation of azol(in)e biosynthesis in ribosomal natural products.
877:
refers exclusively to ribosomally synthesized peptides with 35-70 residues and a
370:
infection. Duramycin has completed phase II clinical trials for the treatment of
138:
below 10 kDa) that are ribosomally-produced and undergo some degree of enzymatic
3085:
3068:
1516:
1489:
1422:
1304:
1288:
1269:
1254:
1169:
1161:
1157:
1145:
1126:
1034:
1024:
945:
795:
791:
787:
778:
621:
565:
488:
386:
363:
311:
236:
232:
91:
3730:
Proceedings of the
National Academy of Sciences of the United States of America
3559:
2859:
Huang YH, Colgrave ML, Daly NL, Keleshian A, Martinac B, Craik DJ (July 2009).
2497:
1830:
1813:
1780:
861:, exported AIPs bind to extracellular receptors that trigger the production of
521:
479:
2749:
2689:
2325:
2308:
2256:
2036:
1605:
1601:
1404:
1381:
1054:
827:
819:
710:
613:
612:
The N-terminal "ring" can be from 7 to 9 amino acids long and is formed by an
590:
359:
315:
307:
209:
119:
95:
2734:"Conotoxins and the posttranslational modification of secreted gene products"
2505:
3750:
3224:
3199:
3165:
3034:
2877:
2639:
1597:
1593:
1589:
1548:
1476:
1400:
1343:
1327:
1312:
928:
906:
892:
858:
854:
807:
714:
663:
644:
629:
625:
606:
467:
decorate the natural product. As an amatoxin, α-amanitin is an inhibitor of
460:
444:
394:
255:
244:
205:
115:
87:
83:
3958:
3906:
3857:
3808:
3769:
3710:
3675:
3626:
3577:
3528:
3427:
3392:
3356:
3312:
3277:
3233:
3184:
3129:
3053:
2994:
2945:
2896:
2810:
2802:
2767:
2707:
2658:
2607:
2558:
2523:
2466:
2384:
2334:
2274:
2225:
2141:
2133:
2103:
2084:
1974:
1923:"Assessment of the safety and distribution of NVB302 in healthy volunteers"
1888:
1798:
1749:
1033:
contain intramolecular linkages between the sulfur of Cys residues and the
3871:
Wever WJ, Bogart JW, Baccile JA, Chan AN, Schroeder FC, Bowers AA (2015).
3469:
3094:
2845:
2537:
Bagly MC, Dale JW, Merritt EA, Xiong X (2005). "Thiopeptide antibiotics".
2009:
1839:
1140:
During RiPP biosynthesis, the unmodified precursor peptide (containing an
632:
residue. The C-terminal "tail" ranges from 7 to 15 amino acids in length.
352:
of LFF571, a derivative of the thiopeptide GE2270-A, for the treatment of
3940:
3888:
3608:
2927:
2207:
2044:
1870:
1636:
1512:
1472:
1444:
1426:
1372:
1331:
1316:
1098:
823:
811:
799:
749:
702:
675:
667:
640:
594:
493:
319:
247:
131:
2837:
1497:
and dehydrobutyrine moieties by dehydrating Ser/Thr precursor residues.
3461:
3147:, Bekkaoui F, Sharpe A, Wang E, Rowland G, Selvaraj G, Datla R (2011).
2416:
2399:
2376:
2168:
1922:
1731:
1320:
706:
656:
636:
553:
497:
435:
177:
99:
3800:
3702:
3384:
3348:
3269:
3121:
2976:
2589:
2550:
2448:
1380:, referred to as the G protein. The G protein is also responsible for
3724:
Wieland Brown LC, Acker MG, Clardy J, Walsh CT, Fischbach MA (2009).
1436:
1347:
1308:
1277:
1109:
segment which is typically preceded (and occasionally followed) by a
803:
652:
300:
229:
601:, giving rise to their name. They are a member of a larger class of
2910:
Oman TJ, Boettcher JM, Wang H, Okalibe XN, van der Donk WA (2011).
1133:
segment of the precursor peptide which helps direct the peptide to
1125:
C-terminal to the core peptide; these are involved in excision and
2398:
Zimmermann, M.; Hegemann, J. D.; Xie, X.; Marahiel, M. A. (2014).
1562:
1498:
1484:
1297:
1287:
1273:
1239:
1088:
916:
911:
777:
689:
617:
598:
575:
552:
520:
478:
434:
323:
277:
240:
72:
Ribosomally synthesized and post-translationally modified peptides
3491:
Goto Y, Li B, Claesen J, Shi Y, Bibb MJ, van der Donk WA (2010).
2572:
Thoendel M, Kavanaugh JS, Flack CE, Horswill AR (January 2011).
1540:
1412:
845:
peptides are used as signaling molecules in the process called
525:
Patellamide A structure with N-C cyclization highlighted in red
3923:
Dunbar KL, Tietz JI, Cox CL, Burkhart BJ, Mitchell DA (2015).
3443:"Comparison of lantibiotic gene clusters and encoded proteins"
2959:
Garcia De
Gonzalo CV, Zhu L, Oman TJ, van der Donk WA (2014).
932:
are RiPPs with a head-to-tail cyclization and three conserved
15:
2912:"Sublancin is not a lantibiotic but an S-linked glycopeptide"
2239:
Lubelski J, Rink R, Khusainov R, Moll GN, Kuipers OP (2008).
1765:"Genome mining for ribosomally synthesized natural products"
635:
The first amino acid of lasso peptides is almost invariably
972:
lanthipeptide aminovinyl cysteines are formed from Cys and
2961:"NMR structure of the S-linked glycopeptide sublancin 168"
1632:
is yet known for any lasso peptide biosynthetic protein.
910:
and other toxoglossan peptides are the components of the
647:
at this site not being tolerated by known enzymes. Thus,
1501:
and azoline synthesis is effected by the E protein, the
589:
are short peptides containing an N-terminal macrolactam
914:
of predatory marine snails, such as the cone snails or
881:
between the N- and C-termini, sometimes referred to as
857:, unlike other regulatory peptides that are linear. In
36:
2313:
Journal of Industrial Microbiology & Biotechnology
1395:
Many cyanobactins also undergo heterocyclization by a
1045:
was determined using isotopically enriched media and
662:
The threading of the lasso tail is trapped either by
2058:
Bushnell DA, Cramer P, Kornberg RD (February 2002).
3149:"Gene expression analysis of flax seed development"
1812:Wyss DF, Lahm HW, Manneberg M, Labhardt AM (1991).
976:(Dha). The first linaridin to be characterized was
418:itself is a RiPP due to its biosynthetic origin as
358:infections, with comparable safety and efficacy to
258:due to their chemical properties, such as moderate
200:RiPPs constitute one of the major superfamilies of
31:
may be too technical for most readers to understand
2182:Leikoski N, Fewer DP, Sivonen K (February 2009).
1493:, designated the B and C proteins, which install
1253:Lanthipeptides are characterized by the presence
730:is required for oxidation of azolines to azoles.
366:actagardine) which is used for the treatment of
3918:
3916:
3781:
3779:
2727:
2725:
2358:
2356:
2354:
2352:
2302:
2300:
2298:
2296:
2294:
2292:
2115:
2113:
1708:
1706:
1704:
1702:
1700:
1698:
1696:
1694:
1692:
1690:
1688:
1129:. Additionally, eukaryotic RiPPs may contain a
1037:of another residue in the peptide. A number of
620:of the first amino acid of the peptide and the
3591:Dunbar KL, Melby JO, Mitchell DA (June 2012).
3108:Tan NH, Zhou J (2006). "Plant cyclopeptides".
1686:
1684:
1682:
1680:
1678:
1676:
1674:
1672:
1670:
1668:
1353:The B protein is typically referred to as the
849:. AIPs are characterized by the presence of a
250:in origin, RiPPs are typically categorized as
1049:. In the case of subtilosin A, isolated from
82:, are a diverse class of natural products of
8:
3542:Melby JO, Nard NJ, Mitchell DA (June 2011).
605:. Additionally, lasso peptides are formally
1399:(referred to as the D protein), installing
455:addition to the N-terminal leader peptide.
1613:, and the C protein is referred to as the
3948:
3896:
3847:
3759:
3749:
3665:
3616:
3567:
3518:
3508:
3441:Siezen RJ, Kuipers OP, de Vos WM (1996).
3223:
3174:
3164:
3084:
3043:
3033:
2984:
2935:
2886:
2876:
2757:
2697:
2648:
2638:
2597:
2513:
2456:
2415:
2324:
2264:
2215:
2093:
2083:
1964:
1878:
1829:
1788:
1739:
1357:; the C and D proteins together form the
902:stability and resistance to degradation.
822:, dehydropiperidine, or a fully oxidized
59:Learn how and when to remove this message
43:, without removing the technical details.
3929:Journal of the American Chemical Society
3877:Journal of the American Chemical Society
3789:Journal of the American Chemical Society
3691:Journal of the American Chemical Society
2674:"AS-48 bacteriocin: close to perfection"
2574:"Peptide signaling in the staphylococci"
2309:"Prospecting genomes for lasso peptides"
875:Bacterial Head-to-Tail Cyclized Peptides
109:As a consequence of the falling cost of
2621:Thoendel M, Horswill AR (August 2009).
1664:
1439:can also be accomplished by an oxidase
1435:. Oxidation of azoline heterocycles to
1097:All RiPPs are synthesized first at the
936:that form a knotted structure called a
389:, the ultra-narrow spectrum antibiotic
216:, although they tend to be large, with
2732:Buczek O, Bulaj G, Olivera BM (2005).
2307:Maksimov MO, Link AJ (February 2014).
1763:Velásquez JE, van der Donk WA (2011).
1443:located on the G protein. Unusual for
1376:, referred to as the A protein, and a
670:residues (class I lasso peptides), by
414:, is also a RiPP. Additionally, human
3420:10.1146/annurev-biochem-060110-113521
1859:Antimicrobial Agents and Chemotherapy
1455:, the B and C proteins, are unknown.
1093:General scheme for RiPP biosynthesis.
722:-terminal to the Cys, Ser, or Thr. A
699:Linear azole(in)e-containing peptides
41:make it understandable to non-experts
7:
2245:Cellular and Molecular Life Sciences
1342:(FMN)-dependent dehydrogenase which
1284:Linear azol(in)e-containing peptides
686:Linear azol(in)e-containing peptides
492:contain a C-terminal decarboxylated
3548:Current Opinion in Chemical Biology
1769:Current Opinion in Chemical Biology
1487:. These include lanthipeptide-like
1188:has been referred to previously as
762:Microcins have bioactivity against
332:atrial natriuretic peptide receptor
102:, and they possess a wide range of
2002:10.1111/j.1399-3011.1987.tb03338.x
1232:(for conopeptides, specifically).
157:origin. In 2013, a set of uniform
14:
1216:. Historical alternate terms for
1113:segment and is typically ~20-110
603:amino-acid-based lasso structures
243:is increasing. Although they are
1953:Expert Opinion on Drug Discovery
1319:. This is accomplished by three
276:RiPPs in commercial use include
20:
1584:and is thought to activate the
140:post-translational modification
3840:10.1016/j.chembiol.2009.01.007
3658:10.1016/j.chembiol.2011.01.019
1519:is installed by the D protein
381:RiPPs include the antibiotics
144:nonribosomal peptide synthesis
1:
3640:Donia MS, Schmidt EW (2011).
3305:10.1016/j.febslet.2010.08.007
1966:10.1517/17460441.2015.1016496
1105:. This peptide consists of a
1017:non-proteinogenic amino acids
1009:nonribosomal natural products
802:rings formed from dehydrated
766:bacteria but usually display
532:are diverse metabolites from
496:in addition to a macrocyclic
322:due to its high affinity for
188:ost-translationally modified
3510:10.1371/journal.pbio.1000339
3014:Proc. Natl. Acad. Sci. U.S.A
2064:Proc. Natl. Acad. Sci. U.S.A
1142:unmodified core peptide, UCP
1121:. Some RiPPs also contain a
1011:due to the presence of many
666:bonds between ring and tail
616:bond between the N-terminal
326:. Anantin is a RiPP used in
3086:10.7164/antibiotics.46.1666
1447:, cyanobactins can include
1346:certain azoline rings into
220:commonly in excess of 1000
196:Prevalence and applications
4010:
3560:10.1016/j.cbpa.2011.02.027
3008:Claesen J, Bibb M (2010).
2498:10.1038/s41421-021-00253-6
2122:Angew. Chem. Int. Ed. Engl
1831:10.7164/antibiotics.44.172
1818:The Journal of Antibiotics
1781:10.1016/j.cbpa.2010.10.027
1204:has been referred to as a
1166:modified core peptide, MCP
786:Most of the characterized
754:are all RiPPs produced by
597:, these peptides resemble
431:Amatoxins and phallotoxins
226:next-generation sequencing
184:bosomally synthesized and
167:ribosomal natural products
80:ribosomal natural products
2750:10.1007/s00018-005-5283-0
2690:10.1007/s00018-011-0724-4
2326:10.1007/s10295-013-1357-4
2257:10.1007/s00018-007-7171-2
2037:10.3109/10409237809149870
1990:Int. J. Pept. Protein Res
1507:, and the G protein, the
1421:A common modification is
1160:(i.e. cyanobactins), and
299:and duramycin, which are
2188:Appl. Environ. Microbiol
1265:by Cys onto Dha or Dhb.
1236:Family-specific features
895:AS-48 was isolated from
659:as their first residue.
350:Phase II clinical trials
3828:Chemistry & Biology
3751:10.1073/pnas.0900008106
3646:Chemistry & Biology
3597:Nature Chemical Biology
3450:Antonie van Leeuwenhoek
3225:10.1126/science.1226121
3166:10.1186/1471-2229-11-74
3035:10.1073/pnas.1008608107
2878:10.1074/jbc.M109.003384
2640:10.1074/jbc.M109.031757
2365:Natural Product Reports
1720:Natural Product Reports
1630:X-ray crystal structure
1429:groups by an F protein
1334:with ATP, resulting in
814:residues, respectively
163:post-ribosomal peptides
2803:10.1006/jmbi.1999.3383
2134:10.1002/anie.200804138
2085:10.1073/pnas.251664698
2025:CRC Crit. Rev. Biochem
1574:adenosine triphosphate
1568:
1553:Ocin-ThiF-like protein
1293:
1245:
1094:
954:antimicrobial peptides
889:Gram-positive bacteria
783:
695:
558:
526:
484:
440:
411:Streptococcus pyogenes
310:functionalized with a
273:of RiPPs are diverse.
239:, the use of RiPPs as
1947:Sandiford SK (2015).
1582:asparagine synthetase
1566:
1471:. Recognition of the
1469:nonribosomal peptides
1340:flavin mononucleotide
1291:
1263:Michael-type addition
1243:
1156:(i.e. thiopeptides),
1135:cellular compartments
1092:
1051:Bacillus subtilis 168
1039:nonribosomal peptides
868:Staphylococcus aureus
839:Autoinducing Peptides
781:
693:
556:
524:
482:
438:
368:Clostridium difficile
355:Clostridium difficile
271:biological activities
214:nonribosomal peptides
130:RiPPs consist of any
3941:10.1021/jacs.5b04682
3889:10.1021/jacs.5b00940
3609:10.1038/nchembio.944
2928:10.1038/nchembio.509
2437:ACS Chemical Biology
2208:10.1128/AEM.02134-08
1871:10.1128/AAC.04251-14
1653:Nonribosomal peptide
1123:recognition sequence
938:cyclic cysteine knot
922:disulfide crosslinks
262:and relatively high
104:biological functions
3742:2009PNAS..106.2549W
3216:2012Sci...338..387F
3026:2010PNAS..10716297C
2838:10.1021/bi00013a002
2738:Cell. Mol. Life Sci
2678:Cell. Mol. Life Sci
2200:2009ApEnM..75..853L
2076:2002PNAS...99.1218B
1378:C-terminal protease
999:Linum usitatissimum
949:are RiPPS that are
709:, or their reduced
180:"RiPP" stands for "
3462:10.1007/bf00399422
3408:Annu. Rev. Biochem
2417:10.1039/C4SC01428F
2377:10.1039/c2np20070h
2169:10.1039/C2SC21183A
1732:10.1039/c2np20085f
1624:(D protein) or an
1569:
1445:ribosomal peptides
1294:
1246:
1226:structural peptide
1214:intervening region
1198:structural peptide
1095:
818:thiopeptides as a
784:
756:Enterobacteriaceae
696:
559:
527:
485:
441:
293:topical antibiotic
171:ribosomal peptides
3984:Molecular biology
3801:10.1021/ja900488a
3703:10.1021/ja807890a
3385:10.1021/ja029654t
3349:10.1021/bi0359527
3270:10.1021/ja104616z
3122:10.1021/cr040699h
3020:(37): 16297–302.
2977:10.1021/cb4008106
2871:(31): 20699–707.
2590:10.1021/cr100370n
2551:10.1021/cr0300441
2449:10.1021/cb200339d
2410:(10): 4032–4043.
1641:peptide synthesis
1432:prenyltransferase
1186:precursor peptide
1168:) then undergoes
1152:, thiopeptides),
1103:precursor peptide
863:virulence factors
794:, are dehydrated
782:Thiostrepton RiPP
624:side chain of an
469:RNA polymerase II
228:methods has made
218:molecular weights
111:genome sequencing
78:), also known as
69:
68:
61:
4001:
3963:
3962:
3952:
3920:
3911:
3910:
3900:
3868:
3862:
3861:
3851:
3819:
3813:
3812:
3783:
3774:
3773:
3763:
3753:
3721:
3715:
3714:
3686:
3680:
3679:
3669:
3637:
3631:
3630:
3620:
3588:
3582:
3581:
3571:
3539:
3533:
3532:
3522:
3512:
3488:
3482:
3481:
3447:
3438:
3432:
3431:
3403:
3397:
3396:
3373:J. Am. Chem. Soc
3367:
3361:
3360:
3331:
3325:
3324:
3288:
3282:
3281:
3258:J. Am. Chem. Soc
3252:
3246:
3245:
3227:
3210:(6105): 387–90.
3195:
3189:
3188:
3178:
3168:
3140:
3134:
3133:
3105:
3099:
3098:
3088:
3064:
3058:
3057:
3047:
3037:
3005:
2999:
2998:
2988:
2956:
2950:
2949:
2939:
2907:
2901:
2900:
2890:
2880:
2856:
2850:
2849:
2821:
2815:
2814:
2786:
2780:
2779:
2761:
2729:
2720:
2719:
2701:
2669:
2663:
2662:
2652:
2642:
2633:(33): 21828–38.
2618:
2612:
2611:
2601:
2569:
2563:
2562:
2534:
2528:
2527:
2517:
2477:
2471:
2470:
2460:
2428:
2422:
2421:
2419:
2395:
2389:
2388:
2360:
2347:
2346:
2328:
2304:
2287:
2286:
2268:
2236:
2230:
2229:
2219:
2179:
2173:
2172:
2152:
2146:
2145:
2117:
2108:
2107:
2097:
2087:
2055:
2049:
2048:
2020:
2014:
2013:
1985:
1979:
1978:
1968:
1944:
1938:
1937:
1935:
1934:
1919:
1913:
1912:
1910:
1909:
1899:
1893:
1892:
1882:
1850:
1844:
1843:
1833:
1809:
1803:
1802:
1792:
1760:
1754:
1753:
1743:
1710:
1588:side chain of a
1523:via a putative
1509:cyclodehydratase
1475:origin of these
1465:natural products
1382:macrocyclization
1359:cyclodehydratase
1154:cyclodehydration
1047:NMR spectroscopy
406:virulence factor
383:cyclothiazomycin
340:In 2012-2013, a
260:molecular weight
224:. The advent of
202:natural products
136:molecular weight
64:
57:
53:
50:
44:
24:
23:
16:
4009:
4008:
4004:
4003:
4002:
4000:
3999:
3998:
3969:
3968:
3967:
3966:
3922:
3921:
3914:
3870:
3869:
3865:
3821:
3820:
3816:
3795:(16): 5946–55.
3785:
3784:
3777:
3723:
3722:
3718:
3697:(12): 4327–34.
3688:
3687:
3683:
3639:
3638:
3634:
3590:
3589:
3585:
3541:
3540:
3536:
3503:(3): e1000339.
3490:
3489:
3485:
3445:
3440:
3439:
3435:
3405:
3404:
3400:
3369:
3368:
3364:
3343:(12): 3385–95.
3333:
3332:
3328:
3290:
3289:
3285:
3264:(37): 12941–5.
3254:
3253:
3249:
3197:
3196:
3192:
3142:
3141:
3137:
3107:
3106:
3102:
3079:(11): 1666–71.
3066:
3065:
3061:
3007:
3006:
3002:
2958:
2957:
2953:
2916:Nat. Chem. Biol
2909:
2908:
2904:
2858:
2857:
2853:
2832:(13): 4147–58.
2823:
2822:
2818:
2788:
2787:
2783:
2744:(24): 3067–79.
2731:
2730:
2723:
2684:(17): 2845–57.
2671:
2670:
2666:
2620:
2619:
2615:
2571:
2570:
2566:
2536:
2535:
2531:
2479:
2478:
2474:
2443:(12): 1307–13.
2430:
2429:
2425:
2397:
2396:
2392:
2371:(9): 996–1006.
2362:
2361:
2350:
2306:
2305:
2290:
2238:
2237:
2233:
2181:
2180:
2176:
2154:
2153:
2149:
2119:
2118:
2111:
2057:
2056:
2052:
2022:
2021:
2017:
1987:
1986:
1982:
1946:
1945:
1941:
1932:
1930:
1921:
1920:
1916:
1907:
1905:
1901:
1900:
1896:
1852:
1851:
1847:
1811:
1810:
1806:
1762:
1761:
1757:
1712:
1711:
1666:
1661:
1649:
1622:ABC transporter
1586:carboxylic acid
1561:
1461:
1390:natural product
1367:
1286:
1251:
1238:
1182:
1119:cellular export
1087:
1085:Common features
1079:
934:disulfide bonds
836:
776:
768:narrow-spectrum
747:
701:(LAPs) contain
688:
584:
551:
519:
477:
463:, and numerous
433:
428:
426:Classifications
416:thyroid hormone
372:cystic fibrosis
346:clinical trials
252:small molecules
198:
128:
65:
54:
48:
45:
37:help improve it
34:
25:
21:
12:
11:
5:
4007:
4005:
3997:
3996:
3991:
3986:
3981:
3971:
3970:
3965:
3964:
3935:(24): 7672–7.
3912:
3883:(10): 3494–7.
3863:
3814:
3775:
3736:(8): 2549–53.
3716:
3681:
3632:
3583:
3534:
3483:
3433:
3398:
3379:(16): 4726–7.
3362:
3326:
3299:(18): 3995–9.
3283:
3247:
3190:
3153:BMC Plant Biol
3135:
3100:
3059:
3000:
2971:(3): 796–801.
2965:ACS Chem. Biol
2951:
2902:
2851:
2816:
2797:(5): 1327–36.
2781:
2721:
2664:
2613:
2564:
2545:(2): 685–714.
2529:
2486:Cell Discovery
2472:
2423:
2390:
2348:
2288:
2231:
2174:
2163:(12): 3522–5.
2147:
2109:
2070:(3): 1218–22.
2050:
2031:(3): 185–260.
2015:
1980:
1939:
1927:ISRCTNregistry
1914:
1894:
1865:(3): 1435–40.
1845:
1804:
1755:
1663:
1662:
1660:
1657:
1656:
1655:
1648:
1645:
1611:lasso protease
1560:
1559:Lasso peptides
1557:
1495:dehydroalanine
1460:
1457:
1366:
1363:
1336:stoichiometric
1285:
1282:
1259:dehydroalanine
1250:
1249:Lanthipeptides
1247:
1237:
1234:
1202:leader peptide
1181:
1178:
1150:lanthipeptides
1111:leader peptide
1086:
1083:
1078:
1075:
1021:epimerizations
974:dehydroalanine
847:quorum sensing
843:quorum sensing
835:
832:
775:
772:
746:
743:
687:
684:
672:steric effects
649:bioinformatics
587:Lasso peptides
583:
582:Lasso peptides
580:
562:Lanthipeptides
550:
549:Lanthipeptides
547:
518:
515:
476:
473:
465:hydroxylations
432:
429:
427:
424:
304:feed additives
264:hydrophobicity
197:
194:
127:
124:
67:
66:
28:
26:
19:
13:
10:
9:
6:
4:
3:
2:
4006:
3995:
3992:
3990:
3987:
3985:
3982:
3980:
3977:
3976:
3974:
3960:
3956:
3951:
3946:
3942:
3938:
3934:
3930:
3926:
3919:
3917:
3913:
3908:
3904:
3899:
3894:
3890:
3886:
3882:
3878:
3874:
3867:
3864:
3859:
3855:
3850:
3845:
3841:
3837:
3833:
3829:
3825:
3818:
3815:
3810:
3806:
3802:
3798:
3794:
3790:
3782:
3780:
3776:
3771:
3767:
3762:
3757:
3752:
3747:
3743:
3739:
3735:
3731:
3727:
3720:
3717:
3712:
3708:
3704:
3700:
3696:
3692:
3685:
3682:
3677:
3673:
3668:
3663:
3659:
3655:
3652:(4): 508–19.
3651:
3647:
3643:
3636:
3633:
3628:
3624:
3619:
3614:
3610:
3606:
3603:(6): 569–75.
3602:
3598:
3594:
3587:
3584:
3579:
3575:
3570:
3565:
3561:
3557:
3554:(3): 369–78.
3553:
3549:
3545:
3538:
3535:
3530:
3526:
3521:
3516:
3511:
3506:
3502:
3498:
3494:
3487:
3484:
3479:
3475:
3471:
3467:
3463:
3459:
3456:(2): 171–84.
3455:
3451:
3444:
3437:
3434:
3429:
3425:
3421:
3417:
3413:
3409:
3402:
3399:
3394:
3390:
3386:
3382:
3378:
3374:
3366:
3363:
3358:
3354:
3350:
3346:
3342:
3338:
3330:
3327:
3322:
3318:
3314:
3310:
3306:
3302:
3298:
3294:
3287:
3284:
3279:
3275:
3271:
3267:
3263:
3259:
3251:
3248:
3243:
3239:
3235:
3231:
3226:
3221:
3217:
3213:
3209:
3205:
3201:
3194:
3191:
3186:
3182:
3177:
3172:
3167:
3162:
3158:
3154:
3150:
3146:
3139:
3136:
3131:
3127:
3123:
3119:
3116:(3): 840–95.
3115:
3111:
3104:
3101:
3096:
3092:
3087:
3082:
3078:
3074:
3070:
3063:
3060:
3055:
3051:
3046:
3041:
3036:
3031:
3027:
3023:
3019:
3015:
3011:
3004:
3001:
2996:
2992:
2987:
2982:
2978:
2974:
2970:
2966:
2962:
2955:
2952:
2947:
2943:
2938:
2933:
2929:
2925:
2921:
2917:
2913:
2906:
2903:
2898:
2894:
2889:
2884:
2879:
2874:
2870:
2866:
2865:J. Biol. Chem
2862:
2855:
2852:
2847:
2843:
2839:
2835:
2831:
2827:
2820:
2817:
2812:
2808:
2804:
2800:
2796:
2792:
2785:
2782:
2777:
2773:
2769:
2765:
2760:
2755:
2751:
2747:
2743:
2739:
2735:
2728:
2726:
2722:
2717:
2713:
2709:
2705:
2700:
2695:
2691:
2687:
2683:
2679:
2675:
2668:
2665:
2660:
2656:
2651:
2646:
2641:
2636:
2632:
2628:
2627:J. Biol. Chem
2624:
2617:
2614:
2609:
2605:
2600:
2595:
2591:
2587:
2584:(1): 117–51.
2583:
2579:
2575:
2568:
2565:
2560:
2556:
2552:
2548:
2544:
2540:
2533:
2530:
2525:
2521:
2516:
2511:
2507:
2503:
2499:
2495:
2491:
2487:
2483:
2476:
2473:
2468:
2464:
2459:
2454:
2450:
2446:
2442:
2438:
2434:
2427:
2424:
2418:
2413:
2409:
2405:
2401:
2394:
2391:
2386:
2382:
2378:
2374:
2370:
2366:
2359:
2357:
2355:
2353:
2349:
2344:
2340:
2336:
2332:
2327:
2322:
2319:(2): 333–44.
2318:
2314:
2310:
2303:
2301:
2299:
2297:
2295:
2293:
2289:
2284:
2280:
2276:
2272:
2267:
2262:
2258:
2254:
2251:(3): 455–76.
2250:
2246:
2242:
2235:
2232:
2227:
2223:
2218:
2213:
2209:
2205:
2201:
2197:
2193:
2189:
2185:
2178:
2175:
2170:
2166:
2162:
2158:
2151:
2148:
2143:
2139:
2135:
2131:
2127:
2123:
2116:
2114:
2110:
2105:
2101:
2096:
2091:
2086:
2081:
2077:
2073:
2069:
2065:
2061:
2054:
2051:
2046:
2042:
2038:
2034:
2030:
2026:
2019:
2016:
2011:
2007:
2003:
1999:
1995:
1991:
1984:
1981:
1976:
1972:
1967:
1962:
1959:(4): 315–20.
1958:
1954:
1950:
1943:
1940:
1928:
1924:
1918:
1915:
1904:
1898:
1895:
1890:
1886:
1881:
1876:
1872:
1868:
1864:
1860:
1856:
1849:
1846:
1841:
1837:
1832:
1827:
1824:(2): 172–80.
1823:
1819:
1815:
1808:
1805:
1800:
1796:
1791:
1786:
1782:
1778:
1774:
1770:
1766:
1759:
1756:
1751:
1747:
1742:
1737:
1733:
1729:
1726:(1): 108–60.
1725:
1721:
1717:
1709:
1707:
1705:
1703:
1701:
1699:
1697:
1695:
1693:
1691:
1689:
1687:
1685:
1683:
1681:
1679:
1677:
1675:
1673:
1671:
1669:
1665:
1658:
1654:
1651:
1650:
1646:
1644:
1642:
1638:
1633:
1631:
1627:
1623:
1618:
1616:
1615:lasso cyclase
1612:
1607:
1603:
1599:
1598:adenylylation
1595:
1591:
1587:
1583:
1579:
1575:
1565:
1558:
1556:
1554:
1550:
1546:
1542:
1538:
1533:
1528:
1526:
1525:cycloaddition
1522:
1518:
1514:
1510:
1506:
1505:
1504:dehydrogenase
1500:
1496:
1492:
1491:
1486:
1480:
1478:
1474:
1470:
1466:
1458:
1456:
1454:
1453:gene clusters
1450:
1449:D-amino acids
1446:
1442:
1438:
1434:
1433:
1428:
1424:
1419:
1417:
1414:
1410:
1406:
1402:
1398:
1397:heterocyclase
1393:
1391:
1385:
1383:
1379:
1375:
1374:
1364:
1362:
1360:
1356:
1355:dehydrogenase
1351:
1349:
1345:
1341:
1337:
1333:
1329:
1324:
1322:
1318:
1314:
1310:
1306:
1302:
1299:
1290:
1283:
1281:
1279:
1275:
1271:
1266:
1264:
1260:
1256:
1248:
1242:
1235:
1233:
1231:
1227:
1223:
1219:
1215:
1211:
1207:
1203:
1199:
1195:
1194:prepropeptide
1191:
1187:
1179:
1177:
1175:
1171:
1167:
1163:
1159:
1155:
1151:
1147:
1143:
1138:
1136:
1132:
1128:
1124:
1120:
1116:
1112:
1108:
1104:
1100:
1091:
1084:
1082:
1076:
1074:
1072:
1068:
1064:
1060:
1056:
1052:
1048:
1044:
1040:
1036:
1032:
1031:Sactipeptides
1028:
1026:
1022:
1018:
1014:
1013:D-amino acids
1010:
1006:
1002:
1000:
995:
991:
989:
985:
984:Microviridins
981:
979:
975:
970:
966:
963:
959:
958:Sublancin 168
955:
952:
948:
947:
942:
939:
935:
931:
930:
925:
923:
919:
918:
913:
909:
908:
903:
900:
899:
894:
890:
886:
885:
880:
876:
872:
870:
869:
864:
860:
856:
852:
848:
844:
840:
833:
831:
829:
825:
821:
815:
813:
810:and cyclized
809:
805:
801:
797:
793:
789:
780:
773:
771:
769:
765:
764:Gram-negative
760:
757:
753:
752:
744:
742:
739:
735:
734:Plantazolicin
731:
729:
725:
724:dehydrogenase
721:
716:
712:
708:
704:
700:
692:
685:
683:
681:
677:
673:
669:
665:
660:
658:
654:
650:
646:
642:
638:
633:
631:
627:
623:
619:
615:
610:
608:
604:
600:
596:
592:
588:
581:
579:
577:
573:
569:
567:
563:
555:
548:
546:
544:
543:patellamide A
538:
535:
534:cyanobacteria
531:
523:
516:
514:
512:
511:
505:
501:
499:
495:
491:
490:
481:
474:
472:
470:
466:
462:
458:
453:
452:
447:
446:
437:
430:
425:
423:
421:
420:thyroglobulin
417:
413:
412:
407:
404:S, the toxic
403:
399:
398:patellamide A
396:
392:
391:plantazolicin
388:
384:
380:
375:
373:
369:
365:
361:
357:
356:
351:
347:
343:
338:
336:
333:
329:
325:
321:
317:
313:
309:
305:
302:
298:
294:
291:
287:
283:
279:
274:
272:
269:The uses and
267:
265:
261:
257:
253:
249:
246:
242:
238:
234:
231:
227:
223:
219:
215:
211:
207:
203:
195:
193:
191:
187:
183:
179:
174:
172:
168:
164:
160:
156:
152:
147:
145:
141:
137:
133:
125:
123:
121:
117:
112:
107:
105:
101:
97:
93:
89:
85:
81:
77:
73:
63:
60:
52:
42:
38:
32:
29:This article
27:
18:
17:
3979:Biosynthesis
3932:
3928:
3880:
3876:
3866:
3834:(2): 141–7.
3831:
3827:
3817:
3792:
3788:
3733:
3729:
3719:
3694:
3690:
3684:
3649:
3645:
3635:
3600:
3596:
3586:
3551:
3547:
3537:
3500:
3496:
3486:
3453:
3449:
3436:
3411:
3407:
3401:
3376:
3372:
3365:
3340:
3337:Biochemistry
3336:
3329:
3296:
3292:
3286:
3261:
3257:
3250:
3207:
3203:
3193:
3156:
3152:
3138:
3113:
3109:
3103:
3076:
3072:
3062:
3017:
3013:
3003:
2968:
2964:
2954:
2922:(2): 78–80.
2919:
2915:
2905:
2868:
2864:
2854:
2829:
2826:Biochemistry
2825:
2819:
2794:
2791:J. Mol. Biol
2790:
2784:
2741:
2737:
2681:
2677:
2667:
2630:
2626:
2616:
2581:
2577:
2567:
2542:
2538:
2532:
2489:
2485:
2475:
2440:
2436:
2426:
2407:
2403:
2393:
2368:
2364:
2316:
2312:
2248:
2244:
2234:
2194:(3): 853–7.
2191:
2187:
2177:
2160:
2156:
2150:
2128:(5): 914–7.
2125:
2121:
2067:
2063:
2053:
2028:
2024:
2018:
1996:(3): 323–9.
1993:
1989:
1983:
1956:
1952:
1942:
1931:. Retrieved
1929:. 2012-10-23
1926:
1917:
1906:. Retrieved
1897:
1862:
1858:
1848:
1821:
1817:
1807:
1775:(1): 11–21.
1772:
1768:
1758:
1723:
1719:
1639:to chemical
1634:
1626:isopeptidase
1619:
1614:
1610:
1596:residue via
1570:
1552:
1532:biosynthesis
1530:Thiopeptide
1529:
1520:
1515:-containing
1508:
1502:
1490:dehydratases
1488:
1481:
1462:
1459:Thiopeptides
1430:
1420:
1396:
1394:
1386:
1377:
1370:
1368:
1365:Cyanobactins
1358:
1354:
1352:
1325:
1307:amino acids
1305:nucleophilic
1301:heterocycles
1295:
1276:and central
1270:dehydratases
1267:
1252:
1230:toxin region
1229:
1225:
1221:
1218:core peptide
1217:
1213:
1209:
1205:
1201:
1197:
1193:
1189:
1185:
1183:
1180:Nomenclature
1173:
1165:
1141:
1139:
1130:
1122:
1110:
1107:core peptide
1106:
1102:
1096:
1080:
1077:Biosynthesis
1070:
1066:
1062:
1058:
1043:subtilosin A
1042:
1030:
1029:
1004:
1003:
998:
993:
992:
987:
983:
982:
977:
968:
967:
961:
957:
951:glycosylated
944:
943:
927:
926:
915:
907:Conopeptides
905:
904:
898:Enterococcus
896:
884:bacteriocins
882:
879:peptide bond
874:
873:
866:
851:cyclic ester
838:
837:
816:
788:thiopeptides
785:
774:Thiopeptides
761:
750:
748:
738:Streptolysin
732:
728:gene cluster
719:
698:
697:
661:
634:
611:
586:
585:
572:Lantibiotics
570:
561:
560:
539:
530:Cyanobactins
529:
528:
517:Cyanobactins
510:Streptomyces
508:
506:
502:
489:Bottromycins
487:
486:
475:Bottromycins
451:phallotoxins
449:
443:
442:
409:
402:Streptolysin
376:
367:
353:
348:was LFF571.
339:
328:cell biology
286:thiostrepton
282:preservative
275:
268:
254:rather than
199:
189:
185:
181:
175:
170:
166:
162:
159:nomenclature
155:biosynthetic
151:nomenclature
148:
129:
108:
90:, including
79:
75:
71:
70:
55:
46:
30:
3414:: 479–505.
3073:J. Antibiot
1539:-dependent
1517:heterocycle
1423:prenylation
1411:-dependent
1371:N-terminal
1255:lanthionine
1174:mature RiPP
1170:proteolysis
1162:cyclization
1158:prenylation
1146:dehydration
1127:cyclization
1025:ion channel
986:are cyclic
841:(AIPs) and
834:Other RiPPs
796:amino acids
792:macrocycles
726:in the LAP
678:or thermal
622:carboxylate
566:lanthionine
387:bottromycin
364:lantibiotic
342:derivatized
314:is used in
312:fluorophore
297:nosiheptide
237:engineering
92:prokaryotes
3973:Categories
3145:Deyholos M
1933:2015-06-08
1908:2015-06-08
1659:References
1606:isopeptide
1602:macrocycle
1405:thiazoline
1222:propeptide
1210:pro-region
1206:propeptide
1190:prepeptide
1055:amide bond
1015:and other
1005:Proteusins
969:Linaridins
962:glycocin F
929:Cyclotides
828:tryptophan
820:piperidine
711:thiazoline
614:isopeptide
591:macrocycle
457:α-Amanitin
393:, and the
360:vancomycin
316:microscopy
308:Phalloidin
290:veterinary
210:terpenoids
126:Definition
120:terpenoids
96:eukaryotes
3497:PLOS Biol
3293:FEBS Lett
3110:Chem. Rev
2578:Chem. Rev
2539:Chem. Rev
2506:2056-5968
2492:(1): 20.
2404:Chem. Sci
2157:Chem. Sci
1604:-forming
1594:aspartate
1590:glutamate
1549:catalysis
1477:molecules
1473:ribosomal
1416:homologue
1401:oxazoline
1328:catalyzes
1313:threonine
1303:from the
1298:azol(in)e
1220:included
1061:ulfur to
994:Orbitides
978:cypemycin
946:Glycocins
893:Enterocin
859:pathogens
855:thioester
808:threonine
751:Microcins
745:Microcins
715:oxazoline
703:thiazoles
680:unfolding
676:proteases
664:disulfide
645:mutations
630:glutamate
626:aspartate
607:rotaxanes
461:sulfoxide
445:Amatoxins
395:cytotoxin
379:bioactive
335:inhibitor
280:, a food
256:biologics
245:ribosomal
206:alkaloids
192:eptide".
116:alkaloids
88:organisms
84:ribosomal
49:July 2015
3994:Peptides
3959:26024319
3907:25742119
3858:19246004
3809:19338336
3770:19196969
3711:19265401
3676:21513887
3627:22522320
3578:21429787
3529:20351769
3428:22404629
3393:12696888
3357:15035610
3321:30215533
3313:20699099
3278:20795624
3242:23925994
3234:22983711
3185:21529361
3130:16522011
3054:20805503
2995:24405370
2946:21196935
2897:19491108
2811:10600388
2776:25647743
2768:16314929
2759:11139066
2716:24837331
2708:21590312
2699:11115006
2659:19520867
2608:21174435
2559:15700961
2524:33820910
2467:21950656
2385:22833149
2343:13286422
2335:24142336
2275:17965835
2266:11131864
2226:19047393
2142:19115340
2104:11805306
1975:25697059
1889:25534727
1799:21095156
1750:23165928
1647:See also
1637:topology
1578:homology
1513:nitrogen
1427:hydroxyl
1373:protease
1344:oxidizes
1332:carbonyl
1317:cysteine
1115:residues
1099:ribosome
1071:tibiotic
1069:arbon an
1035:α-carbon
824:pyridine
812:cysteine
800:thiazole
707:oxazoles
668:cysteine
641:cysteine
595:topology
494:thiazole
344:RiPP in
248:peptides
146:(NRPS).
132:peptides
3989:Enzymes
3950:4481143
3898:4425689
3849:2676563
3761:2650375
3738:Bibcode
3667:3119926
3618:3428213
3569:3947797
3520:2843593
3478:8887022
3470:8775977
3212:Bibcode
3204:Science
3176:3107784
3095:7802859
3045:2941285
3022:Bibcode
2986:3985867
2937:3060661
2888:2742835
2846:7703226
2650:2756194
2599:3086461
2515:8021565
2458:3241860
2283:9549591
2217:2632131
2196:Bibcode
2072:Bibcode
2010:3692680
1880:4325808
1840:1826288
1790:3090663
1741:3954855
1521:cyclase
1388:single
1321:enzymes
657:alanine
643:, with
637:glycine
498:amidine
204:, like
178:acronym
100:archaea
35:Please
3957:
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1441:domain
1437:azoles
1348:azoles
1309:serine
1278:kinase
1228:, and
1200:. The
1148:(i.e.
1131:signal
804:serine
653:serine
599:lassos
377:Other
330:as an
301:animal
295:, and
233:mining
230:genome
212:, and
169:, and
134:(i.e.
98:, and
3474:S2CID
3446:(PDF)
3317:S2CID
3238:S2CID
2772:S2CID
2712:S2CID
2339:S2CID
2279:S2CID
1499:Azole
1485:genes
1467:were
1315:, or
1274:lyase
1212:, or
1196:, or
1101:as a
1065:lpha-
917:Conus
912:venom
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618:amine
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324:actin
320:stain
318:as a
278:nisin
241:drugs
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3903:PMID
3854:PMID
3805:PMID
3766:PMID
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3672:PMID
3623:PMID
3574:PMID
3525:PMID
3466:PMID
3424:PMID
3389:PMID
3353:PMID
3309:PMID
3274:PMID
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3181:PMID
3126:PMID
3091:PMID
3050:PMID
2991:PMID
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2893:PMID
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2807:PMID
2764:PMID
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2138:PMID
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960:and
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