148:
507:
532:
24:
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also contain DHIV in their structure, as well as dolabellin. Figure 2 compares the structures of deacetylhectochlorin, hectochlorin, lyngbyabellin B and dolabellin. This figure illustrates the similarities (black) and differences (red) between those compounds compared to deacetylhectochlorin. All of
485:
ring (Figure 1C). HctF gene has remarkable similarity to hctE, although, there are two main differences: the iso-valeric acid incorporated does not condensate by the hydroxyl group that substitute an amino group, instead, it condensates be the hydroxyl group in the side chain created by a P450
535:
Figure 2. Comparison between all known compounds containing hexanoic acid as start unit that becomes halogenated twice in the position 5, producing a fairly rare gem-dichloro group. The figure illustrates the similarities (black) and differences (red) between those compounds compared to
49:
494:
bond to ester bond and catalyze the attack from the C-terminal free hydroxyl group to this newly formed ester, cyclizing the molecule. The final genes hctG and hctH probably encode two P450 that oxidize the side chain of both isovaleric acids (Figure 1D). Lastly, a
469:, therefore, incorporating isovaleric acid instead an amino acid. This hydroxyl group that substitutes an amino group condensates with the previous carbonyl from the KS extension. The second module has 67% identity to CurF and BarG (from Curacin A and
553:
Ramaswamy, A. V., Sorrels, C. M. & Gerwick, W. H. Cloning and biochemical characterization of the hectochlorin biosynthetic gene cluster from the marine cyanobacterium
Lyngbya majuscula. J. Nat. Prod. 70, 1977–1986
379:
The biosynthetic gene cluster (BGC) is composed of eight genes (Figure 1A), of which seven are directly related to the synthesis of the molecule (hctA-B and hctD-H, in green) and one is predicted to encode a
171:
InChI=1S/C27H34Cl2N2O9S2/c1-13-17(9-8-10-27(7,28)29)38-23(34)15-11-42-21(30-15)19(37-14(2)32)26(5,6)40-24(35)16-12-41-20(31-16)18(25(3,4)36)39-22(13)33/h11-13,17-19,36H,8-10H2,1-7H3/t13-,17-,18+,19+/m0/s1
518:
Currently in the MarinLit database, other compounds (besides deacetylhectochlorin and hectochlorin) that contain this fairly unusual gem-dichloro group are lyngbyabellin A-N, 27-deoxylyngbyabellin A and
181:
InChI=1/C27H34Cl2N2O9S2/c1-13-17(9-8-10-27(7,28)29)38-23(34)15-11-42-21(30-15)19(37-14(2)32)26(5,6)40-24(35)16-12-41-20(31-16)18(25(3,4)36)39-22(13)33/h11-13,17-19,36H,8-10H2,1-7H3/t13-,17-,18+,19+/m0/s1
603:
Suntornchashwej, S., Chaichit, N., Isobe, M. & Suwanborirux, K. Hectochlorin and morpholine derivatives from the Thai sea hare, Bursatella leachii. J. Nat. Prod. 68, 951–955 (2005).
503:. This addition is not predicted in the current biosynthesis, although the absence of this post-NRPS modification would produce the analogue previously mentioned, deacetylhectochlorin.
441:. As mentioned before, hctC is a transposase of unknown function and it is not directly related in the molecule synthesis. Next, this 5,5-dichlorohexanoic acquires one
341:, which concentrate the cyanobacterial metabolites as a mechanism of defense from predators. Therefore, in 2005, hectochlorin was re-isolated from the Thai sea hare
384:(hctC, in yellow), that tends to be related to the mobility of the gene and not the synthesis of molecule features. The cluster is also flanked by other 5 ORF (
197:
572:
Marquez, B. L. et al. Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly. J. Nat. Prod. 65, 866–871 (2002).
563:
Marquez, B. L. et al. Structure and absolute stereochemistry of hectochlorin, a potent stimulator of actin assembly. J. Nat. Prod. 65, 866–871 (2002).
583:
A Maldiisotopic
Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens
481:
a cysteine, as well as oxidize it by FMN-dependent oxidase present in between adenlyation conserved motifs, catalyzing the formation of a
329:
JHB, collected from Hector Bay, Jamaica, 1996, which is a strain also known for being the producer of other two potent biomolecules named
433:
co-factor. In the C-terminus, one ACP domain is present and it is fairly homologous to several others ACP domain at cyanobacteria, like
333:
and
Cryptomaldamide. Due to its activity against plants pathogens, synthetic efforts elucidated the compound’s total synthesis in 2002.
594:
Cetusic, J. R. P., Green, F. R., Graupner, P. R. & Oliver, M. P. Total
Synthesis of Hectochlorin. Org. Lett. 4, 1307–1310 (2002).
162:
446:
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as start unit that becomes halogenated twice in the position 5, producing fairly rare gem-dichloro group, that along with two
445:
by hctD. This gene consists of a single KS module with a minimal configuration (KS-AT-CP) plus one KR and cMT, producing a
399:
Biosynthesis of hectochlorin starts with hctA (Figure 1A), responsible for the start unit, which has 53% similarity to an
347:, along with a new analogue, deacetylhectochlorin. Another reisolation of hectochlorin was reported in 2013, from another
287:
126:
368:
355:, surprising in a non-tropical environment, as opposed to the other Moorea strains isolated before. The predicted
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418:
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and a number of plants pathogens, as well as inhibiting growth of human cell lines by hyperpolymerization of
496:
400:
69:
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Figure1. A) Predicted biosynthesis of hectochlorin. B) P450 oxidation of side chain. C)Formation of
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421:. For such, hctB has one halogenation domain in the N-terminus, which is 47% similar to a
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residue (Asp235) that is related to interactions with the amino group of the cognate
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those compounds (but hectochlorin) do not have a proposed biosynthesis published.
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C1(OC(=O)C2=CSC(=N2)(C(OC(=O)C3=CSC(=N3)(OC1=O)C(C)(C)O)(C)C)OC(=O)C)CCCC(C)(Cl)Cl
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twice at the fifth carbon by the gene hctB, generating the gem-dichloro group in
449:. HctE consists of a bi-modular NRPS, of which the first module incorporates an
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happens in the free hydroxyl group from the second isovaleric acid, adding an
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585:. J Nat Prod. 2017 May 26;80(5):1514-1521. doi: 10.1021/acs.jnatprod.7b00019.
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of unknown function regarding biosynthesis mechanistic of the molecule.
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Except where otherwise noted, data are given for materials in their
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and also contains all conserved residues for the binding of Fe2+/2-
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that starts the hectochlorin molecule. This hexanoic acid gets
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of hectochlorin was published in 2007 and consists in a hybrid
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species are normally the main component of the dietary of some
371:(DHIV) units compose a very interesting bioactive molecule.
131:
461:-domain (A domain) has a mutation substituting a conserved
523:, all of those synthesized from Moorea species. Most
388:), including three hypothetical proteins, a homing
453:and the second module incorporates a heterocyclic
320:. It was originally isolated from the filamentous
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447:7,7-dichloro-3-hydroxy-2-methyl-octanoic acid
8:
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486:oxidation (Figure 1B); hctF has an extra
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174:Key: USXIYWCPCGVOKF-NOENWEJRSA-N
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184:Key: USXIYWCPCGVOKF-NOENWEJRBM
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351:strain (RS05), isolated from the
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409:and is predicted to generate a
284:(at 25 °C , 100 kPa).
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226:
1:
369:2,3-dihydroxyisovaleric acid
457:. In the first module, the
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473:BGCs) and is predicted to
419:5,5-dichlorohexanoic acid
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21:
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497:post-NRPS modification
427:Microcystis aeruginosa
536:deacetylhectochlorin.
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509:
490:domain that converts
394:reverse transcriptase
306:that exhibits potent
401:Acyl-ACP synthetase
386:Open reading rrames
274: g·mol
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344:Bursatella leachii
288:Infobox references
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581:Kinnel RB et al;
310:activity against
296:Chemical compound
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127:CompTox Dashboard
50:Interactive image
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479:heterocyclize
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411:hexanoic acid
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365:hexanoic acid
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331:Jamaicamide A
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17:Hectochlorin
625:Lipopeptides
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501:acetyl group
488:thioesterase
443:KS extension
431:oxoglutarate
426:
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390:endonuclease
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375:Biosynthesis
357:biosynthesis
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300:Hectochlorin
299:
298:
70:ChEMBL505302
31:Identifiers
459:adenlyation
439:Jamaicamide
415:halogenated
406:Fischerella
382:transposase
313:C. albicans
304:lipopeptide
214:Properties
614:Categories
541:References
521:dolabellin
467:amino acid
423:halogenase
308:antifungal
267:Molar mass
81:ChemSpider
37:3D model (
620:Thiazoles
492:thioester
475:adenylate
471:Barbamide
463:aspartate
435:Curacin A
363:, with a
339:sea hares
512:thiazole
483:thiazole
455:cysteine
361:NRPS-PKS
554:(2007).
353:Red Sea
102:PubChem
392:and a
335:Moorea
272:665.59
198:SMILES
115:636718
90:552449
61:ChEMBL
318:actin
302:is a
163:InChI
39:JSmol
514:ring
477:and
425:at
403:in
132:EPA
105:CID
616::
437:,
239:Cl
236:34
230:27
260:2
257:S
254:9
251:O
248:2
245:N
242:2
233:H
227:C
134:)
130:(
41:)
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