466:
868:(PKS), many secondary metabolites are, in fact, fusions of NRPs and polyketides. In essence, this occurs when PK modules follow NRP modules, and vice versa. Although there is high degree of similarity between the Carrier (PCP/ACP) domains of both types of synthetases, the mechanism of condensation is different from a chemical standpoint:
451:
Note that as many as 10% percent of bacterial NRPS are not laid out as large modular proteins, but as separate enzymes. Some NRPS modules deviate from the standard domain structure, and some extra domains have been described. There are also NRPS enzymes that serve as a scaffold for other
421:. It is synthesized by a single 1.6MDa NRPS. The enzymes are organized in modules that are responsible for the introduction of one additional amino acid. Each module consists of several domains with defined functions, separated by short spacer regions of about 15 amino acids.
995:
Johnson RD, Johnson L, Itoh Y, Kodama M, Otani H, Kohmoto K (July 2000). "Cloning and characterization of a cyclic peptide synthetase gene from
Alternaria alternata apple pathotype whose product is involved in AM-toxin synthesis and pathogenicity".
899:
879:
NRPs, the C domain catalyzes the amide bond formation between the amino acid it adds to the chain (on the PCP of one module) and the nascent peptide(on the PCP of the next module).
1039:
Turgay K, Krause M, Marahiel MA (February 1992). "Four homologous domains in the primary structure of GrsB are related to domains in a superfamily of adenylate-forming enzymes".
155:
Nonribosomal peptides are a very diverse family of natural products with an extremely broad range of biological activities and pharmacological properties. They are often toxins,
852:
is also believed to have substrate specificity, especially if located behind an epimerase E-domain-containing module where it functions as a 'filter' for the epimerized
686:
group of the growing peptide chain from the previous module with the amino group of the current module. The extended peptide is now attached to the current PCP-domain.
840:
and usually only the A-domain determines which amino acid is incorporated in a module. Ten amino acids that control substrate specificity and can be considered the '
1082:
Fischbach MA, Walsh CT (August 2006). "Assembly-line enzymology for polyketide and nonribosomal
Peptide antibiotics: logic, machinery, and mechanisms".
856:. Computational methods, such as SANDPUMA and NRPSpredictor2, have been developed to predict substrate specificity from DNA or protein sequence data.
1493:"Structural and functional aspects of the nonribosomal peptide synthetase condensation domain superfamily: discovery, dissection and diversity"
144:. This is just a sampling of the various manipulations and variations that nonribosomal peptides can perform. Nonribosomal peptides are often
1658:
932:
696:: Sometimes the C-domain is replaced by a Cy-domain, which, in addition to the amide bond formation, catalyzes the reaction of the
1566:
Marahiel MA, Stachelhaus T, Mootz HD (November 1997). "Modular
Peptide Synthetases Involved in Nonribosomal Peptide Synthesis".
1395:"SANDPUMA: ensemble predictions of nonribosomal peptide chemistry reveal biosynthetic diversity across Actinobacteria"
797:. The responsible enzymes are usually associated to the synthetase complex and their genes are organized in the same
1130:"Atlas of nonribosomal peptide and polyketide biosynthetic pathways reveals common occurrence of nonmodular enzymes"
1648:
485:
need to be added. The domain part can be merged with the polyketide domains into a template to avoid duplication..
436:
biosynthesis. Due to these structural and mechanistic similarities, some nonribosomal peptide synthetases contain
200:
745:
the completed polypeptide chain from the PCP-domain of the previous module, thereby often forming cyclic amides (
488:
87:. Each nonribosomal peptide synthetase can synthesize only one type of peptide. Nonribosomal peptides often have
834:
634:
574:
802:
728:: Sometimes an E-domain epimerizes the innermost amino acid of the peptide chain into the D-configuration.
619:
410:
385:
669:
Loading: Analogous to the starting stage, each module loads its specific amino acid onto its PCP-domain.
401:
Nonribosomal peptides are synthesized by one or more specialized nonribosomal peptide-synthetase (NRPS)
365:
41:
1663:
1347:
1141:
961:
873:
865:
373:
849:
837:
769:
437:
1537:
Schwarzer D, Finking R, Marahiel MA (June 2003). "Nonribosomal peptides: from genes to products".
300:
1107:
1064:
1021:
260:
1668:
1626:
1583:
1554:
1514:
1473:
1424:
1375:
1316:
1267:
1218:
1169:
1099:
1056:
1013:
977:
928:
508:
The order of modules and domains of a complete nonribosomal peptide synthetase is as follows:
478:
477:
about The positions of some domains in the next section are not found, and newer domains from
272:
172:
128:. Cyclization of amino acids against the peptide "backbone" is often performed, resulting in
1236:
Felnagle EA, Barkei JJ, Park H, Podevels AM, McMahon MD, Drott DW, Thomas MG (October 2010).
1653:
1616:
1608:
1575:
1546:
1504:
1463:
1455:
1414:
1406:
1365:
1355:
1306:
1298:
1257:
1249:
1208:
1200:
1159:
1149:
1091:
1048:
1005:
969:
627:
88:
1238:"MbtH-like proteins as integral components of bacterial nonribosomal peptide synthetases"
848:
has yielded methodologies to computationally switch the specificities of A-domains. The
64:
these organisms. While there exist a wide range of peptides that are not synthesized by
1351:
1145:
965:
487:
Please expand the section to include this information. Further details may exist on the
1621:
1596:
1468:
1443:
1419:
1394:
1370:
1335:
1311:
1286:
1262:
1237:
1213:
1188:
1164:
1129:
1052:
845:
589:
Red: Reduction of thiazolines or oxazolines to thiazolidines or oxazolidines (optional)
445:
230:
149:
141:
825:
group has to be removed by specialized associated thioesterases (TE-II) (Deblocking).
817:
molecules has to be attached to the PCP-domain by 4'PP transferases (Priming) and the
136:; these can be further oxidized or reduced. On occasion, dehydration is performed on
1642:
794:
782:
725:
679:
353:
338:
145:
125:
113:
92:
84:
45:
17:
1410:
1111:
1068:
1025:
973:
920:
790:
719:
689:
672:
425:
295:
121:
61:
1595:
Caboche S, Pupin M, Leclère V, Fontaine A, Jacques P, Kucherov G (January 2008).
1509:
1492:
1444:"NRPSpredictor2--a web server for predicting NRPS adenylation domain specificity"
715:
693:
656:
652:
418:
349:
324:
312:
285:
277:
215:
190:
156:
1340:
Proceedings of the
National Academy of Sciences of the United States of America
1204:
1189:"Refining and expanding nonribosomal peptide synthetase function and mechanism"
1134:
Proceedings of the
National Academy of Sciences of the United States of America
1009:
72:
typically refers to a very specific set of these as discussed in this article.
889:
814:
742:
648:
Some A domains require interaction with MbtH-like proteins for their activity.
642:
586:
Ox: Oxidation of thiazolines or oxazolines to thiazoles or oxazoles (optional)
548:
544:
433:
429:
334:
290:
255:
250:
243:
237:
225:
220:
210:
205:
195:
185:
168:
164:
133:
95:
57:
1393:
Chevrette MG, Aicheler F, Kohlbacher O, Currie CR, Medema MH (October 2017).
1287:"Activation of the pacidamycin PacL adenylation domain by MbtH-like proteins"
1360:
1154:
786:
701:
683:
645:(4'PP) sidechain of the PCP-domain catalyzed by the PCP-domain (thiolation).
630:
414:
330:
265:
129:
117:
49:
1630:
1587:
1558:
1518:
1477:
1428:
1379:
1320:
1271:
1222:
1173:
1103:
1017:
981:
482:
465:
383:
victorin – a chlorinated cyclic pentapeptide made by the pathogenic fungus
1442:
Röttig M, Medema MH, Blin K, Weber T, Rausch C, Kohlbacher O (July 2011).
1060:
1612:
1459:
894:
765:
710:
705:
104:
80:
65:
844:' of nonribosomal peptide synthesis have been identified, and rational
754:
441:
307:
160:
152:
of identical sequences chained together or cyclized, or even branched.
38:
1579:
1302:
1253:
1095:
1550:
853:
841:
818:
798:
746:
697:
638:
406:
402:
137:
405:. The NRPS genes for a certain peptide are usually organized in one
56:. Nonribosomal peptides are also found in higher organisms, such as
949:
452:
modifications to the substrate to incorporate unusual amino acids.
900:
Ribosomally synthesized and post-translationally modified peptides
761:
750:
676:
363:
HC-toxin – a virulence factor made by the plant pathogenic fungus
319:
53:
822:
623:
1128:
Wang H, Fewer DP, Holm L, Rouhiainen L, Sivonen K (June 2014).
813:
To become functional, the 4'-phospho-pantetheine sidechain of
602:
TE: Termination by a thio-esterase (only found once in a NRPS)
459:
1497:
Biochimica et
Biophysica Acta (BBA) - Proteins and Proteomics
580:
C: Condensation forming the amide bond (required in a module)
1336:"Computational structure-based redesign of enzyme activity"
577:
with attached 4'-phospho-pantetheine (required in a module)
1334:
Chen CY, Georgiev I, Anderson AC, Donald BR (March 2009).
1285:
Zhang W, Heemstra JR, Walsh CT, Imker HJ (November 2010).
428:
of nonribosomal peptides shares characteristics with the
583:
Cy: Cyclization into thiazoline or oxazolines (optional)
925:
Organic chemistry : breakthroughs and perspectives
605:
R: Reduction to terminal aldehyde or alcohol (optional)
1193:
Journal of
Industrial Microbiology & Biotechnology
760:
Also, the peptide can be released by an R-domain that
389:. Its nonribosomal synthesis has not been established.
651:
Sometimes the amino group of the bound amino acid is
741:Termination: The TE-domain (thio-esterase domain)
731:This cycle is repeated for each elongation module.
1187:McErlean M, Overbay J, Van Lanen S (March 2019).
1491:Bloudoff, Kristjan; Schmeing, Martin T. (2017).
618:Loading: The first amino acid is activated with
417:. However the first fungal NRP to be found was
371:AM-toxin – made by the plant pathogenic fungus
781:The final peptide is often modified, e.g., by
608:X: Recruits cytochrome P450 enzymes (optional)
592:E: Epimerization into D-amino acids (optional)
1597:"NORINE: a database of nonribosomal peptides"
8:
91:and/or branched structures, can contain non-
872:PKS, carbon-carbon bond formation through
448:-derived subunits into the peptide chain.
1620:
1508:
1467:
1418:
1369:
1359:
1310:
1261:
1212:
1163:
1153:
75:Nonribosomal peptides are synthesized by
60:, but are thought to be made by bacteria
366:Cochliobolus (Helminthosporium) carbonum
911:
102:-amino acids, carry modifications like
570:A: Adenylation (required in a module)
7:
1123:
1121:
998:Molecular Plant-Microbe Interactions
637:by the A-domain and loaded onto the
1053:10.1111/j.1365-2958.1992.tb01498.x
25:
927:. Weinheim, Germany: Wiley-VCH.
464:
77:nonribosomal peptide synthetases
974:10.1016/j.phytochem.2006.05.033
833:Most domains have a very broad
764:the thioester bond to terminal
1:
1411:10.1093/bioinformatics/btx400
675:: The C-domain catalyzes the
440:modules for the insertion of
1510:10.1016/j.bbapap.2017.05.010
1454:(Web Server issue): W362-7.
201:Calcium dependent antibiotic
1607:(Database issue): D326-31.
864:Due to the similarity with
1685:
1205:10.1007/s10295-018-02130-w
1010:10.1094/MPMI.2000.13.7.742
346:Nitrogen storage polymers
708:sidechain with the amide-
567:F: Formylation (optional)
529:modules: -(C/Cy)--A-PCP--
1659:Glycopeptide antibiotics
1539:Natural Product Reports
1361:10.1073/pnas.0900266106
1155:10.1073/pnas.1401734111
948:Walton JD (July 2006).
829:Substrate specificities
599:-methylation (optional)
575:peptide carrier protein
175:are in commercial use.
163:. Nonribosomal peptide
112:-formyl groups, or are
1601:Nucleic Acids Research
1448:Nucleic Acids Research
1041:Molecular Microbiology
860:Mixed with polyketides
809:Priming and deblocking
682:formation between the
475:is missing information
386:Cochliobolus victoriae
44:, usually produced by
850:condensation C-domain
641:-attached 4'-phospho-
83:, are independent of
42:secondary metabolites
31:Nonribosomal peptides
27:Secondary metabolides
18:Non-ribosomal peptide
874:Claisen condensation
866:polyketide synthases
573:PCP: Thiolation and
374:Alternaria alternata
79:, which, unlike the
70:nonribosomal peptide
1352:2009PNAS..106.3764C
1146:2014PNAS..111.9259W
966:2006PChem..67.1406W
438:polyketide synthase
409:in bacteria and in
352:– produced by some
1613:10.1093/nar/gkm792
1460:10.1093/nar/gkr323
714:, thereby forming
655:by an F-domain or
273:Immunosuppressants
173:immunosuppressants
1649:Molecular biology
1580:10.1021/cr960029e
1503:(11): 1587–1604.
1405:(20): 3202–3210.
1303:10.1021/bi101539b
1254:10.1021/bi1012854
1096:10.1021/cr0503097
736:Termination stage
664:Elongation stages
659:by an NMT-domain.
558:: alternatively)
506:
505:
101:
37:) are a class of
16:(Redirected from
1676:
1634:
1624:
1591:
1574:(7): 2651–2674.
1568:Chemical Reviews
1562:
1551:10.1039/b111145k
1523:
1522:
1512:
1488:
1482:
1481:
1471:
1439:
1433:
1432:
1422:
1390:
1384:
1383:
1373:
1363:
1331:
1325:
1324:
1314:
1282:
1276:
1275:
1265:
1233:
1227:
1226:
1216:
1199:(3–4): 493–513.
1184:
1178:
1177:
1167:
1157:
1125:
1116:
1115:
1084:Chemical Reviews
1079:
1073:
1072:
1036:
1030:
1029:
992:
986:
985:
945:
939:
938:
916:
501:
498:
492:
468:
460:
280:(Cyclosporine A)
99:
21:
1684:
1683:
1679:
1678:
1677:
1675:
1674:
1673:
1639:
1638:
1637:
1594:
1565:
1536:
1532:
1530:Further reading
1527:
1526:
1490:
1489:
1485:
1441:
1440:
1436:
1392:
1391:
1387:
1333:
1332:
1328:
1284:
1283:
1279:
1235:
1234:
1230:
1186:
1185:
1181:
1140:(25): 9259–64.
1127:
1126:
1119:
1081:
1080:
1076:
1038:
1037:
1033:
994:
993:
989:
960:(14): 1406–13.
947:
946:
942:
935:
919:Dai LX (2012).
918:
917:
913:
908:
886:
862:
831:
811:
779:
738:
722:, respectively.
666:
628:phosphoric acid
615:
564:
539:module: -(TE/R)
519:module: -A-PCP-
502:
496:
493:
486:
469:
458:
399:
394:
181:
140:, resulting in
28:
23:
22:
15:
12:
11:
5:
1682:
1680:
1672:
1671:
1666:
1661:
1656:
1651:
1641:
1640:
1636:
1635:
1592:
1563:
1533:
1531:
1528:
1525:
1524:
1483:
1434:
1399:Bioinformatics
1385:
1346:(10): 3764–9.
1326:
1297:(46): 9946–7.
1277:
1248:(41): 8815–7.
1228:
1179:
1117:
1090:(8): 3468–96.
1074:
1031:
987:
954:Phytochemistry
940:
933:
910:
909:
907:
904:
903:
902:
897:
892:
885:
882:
881:
880:
877:
861:
858:
846:protein design
830:
827:
810:
807:
778:
775:
774:
773:
758:
737:
734:
733:
732:
729:
723:
687:
670:
665:
662:
661:
660:
649:
646:
614:
613:Starting stage
611:
610:
609:
606:
603:
600:
593:
590:
587:
584:
581:
578:
571:
568:
563:
560:
554:: optionally;
541:
540:
530:
520:
504:
503:
472:
470:
463:
457:
454:
398:
395:
393:
392:
391:
390:
381:
369:
358:
357:
356:
344:
343:
342:
328:
317:
316:
315:
305:
304:
303:
298:
293:
283:
282:
281:
270:
269:
268:
263:
258:
248:
247:
246:
244:ACV-Tripeptide
235:
234:
233:
231:Zwittermicin A
228:
223:
218:
213:
208:
203:
198:
193:
182:
180:
177:
142:dehydroalanine
46:microorganisms
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
1681:
1670:
1667:
1665:
1662:
1660:
1657:
1655:
1652:
1650:
1647:
1646:
1644:
1632:
1628:
1623:
1618:
1614:
1610:
1606:
1602:
1598:
1593:
1589:
1585:
1581:
1577:
1573:
1569:
1564:
1560:
1556:
1552:
1548:
1545:(3): 275–87.
1544:
1540:
1535:
1534:
1529:
1520:
1516:
1511:
1506:
1502:
1498:
1494:
1487:
1484:
1479:
1475:
1470:
1465:
1461:
1457:
1453:
1449:
1445:
1438:
1435:
1430:
1426:
1421:
1416:
1412:
1408:
1404:
1400:
1396:
1389:
1386:
1381:
1377:
1372:
1367:
1362:
1357:
1353:
1349:
1345:
1341:
1337:
1330:
1327:
1322:
1318:
1313:
1308:
1304:
1300:
1296:
1292:
1288:
1281:
1278:
1273:
1269:
1264:
1259:
1255:
1251:
1247:
1243:
1239:
1232:
1229:
1224:
1220:
1215:
1210:
1206:
1202:
1198:
1194:
1190:
1183:
1180:
1175:
1171:
1166:
1161:
1156:
1151:
1147:
1143:
1139:
1135:
1131:
1124:
1122:
1118:
1113:
1109:
1105:
1101:
1097:
1093:
1089:
1085:
1078:
1075:
1070:
1066:
1062:
1058:
1054:
1050:
1047:(4): 529–46.
1046:
1042:
1035:
1032:
1027:
1023:
1019:
1015:
1011:
1007:
1004:(7): 742–53.
1003:
999:
991:
988:
983:
979:
975:
971:
967:
963:
959:
955:
951:
944:
941:
936:
934:9783527333776
930:
926:
922:
915:
912:
905:
901:
898:
896:
893:
891:
888:
887:
883:
878:
875:
871:
870:
869:
867:
859:
857:
855:
851:
847:
843:
839:
836:
828:
826:
824:
820:
816:
808:
806:
804:
803:gene clusters
800:
796:
795:hydroxylation
792:
788:
784:
783:glycosylation
776:
771:
767:
763:
759:
756:
752:
748:
744:
740:
739:
735:
730:
727:
726:Epimerization
724:
721:
717:
713:
712:
707:
703:
699:
695:
691:
688:
685:
681:
678:
674:
671:
668:
667:
663:
658:
654:
650:
647:
644:
640:
636:
632:
629:
625:
621:
617:
616:
612:
607:
604:
601:
598:
594:
591:
588:
585:
582:
579:
576:
572:
569:
566:
565:
561:
559:
557:
553:
550:
546:
538:
534:
531:
528:
524:
521:
518:
514:
511:
510:
509:
500:
490:
484:
480:
476:
473:This section
471:
467:
462:
461:
455:
453:
449:
447:
443:
439:
435:
431:
427:
422:
420:
416:
412:
411:gene clusters
408:
404:
396:
388:
387:
382:
380:
376:
375:
370:
368:
367:
362:
361:
359:
355:
354:cyanobacteria
351:
348:
347:
345:
340:
339:cyanobacteria
336:
332:
329:
326:
323:
322:
321:
318:
314:
311:
310:
309:
306:
302:
299:
297:
294:
292:
289:
288:
287:
284:
279:
276:
275:
274:
271:
267:
264:
262:
259:
257:
254:
253:
252:
249:
245:
242:
241:
239:
236:
232:
229:
227:
224:
222:
219:
217:
214:
212:
209:
207:
204:
202:
199:
197:
194:
192:
189:
188:
187:
184:
183:
178:
176:
174:
170:
166:
162:
158:
153:
151:
147:
143:
139:
135:
131:
127:
123:
119:
115:
111:
107:
106:
97:
94:
93:proteinogenic
90:
86:
85:messenger RNA
82:
78:
73:
71:
67:
63:
59:
55:
51:
47:
43:
40:
36:
32:
19:
1604:
1600:
1571:
1567:
1542:
1538:
1500:
1496:
1486:
1451:
1447:
1437:
1402:
1398:
1388:
1343:
1339:
1329:
1294:
1291:Biochemistry
1290:
1280:
1245:
1242:Biochemistry
1241:
1231:
1196:
1192:
1182:
1137:
1133:
1087:
1083:
1077:
1044:
1040:
1034:
1001:
997:
990:
957:
953:
943:
924:
914:
863:
832:
812:
791:halogenation
780:
749:) or cyclic
720:thiazolidine
716:oxazolidines
709:
690:Condensation
673:Condensation
596:
555:
552:
542:
536:
532:
526:
522:
516:
512:
507:
494:
474:
450:
426:biosynthesis
423:
400:
397:Biosynthesis
384:
378:
372:
364:
360:Phytotoxins
325:Microcystins
301:Myxochelin A
296:Enterobactin
286:Siderophores
157:siderophores
154:
126:hydroxylated
114:glycosylated
109:
108:-methyl and
103:
76:
74:
69:
34:
30:
29:
1664:Antibiotics
838:specificity
694:Cyclization
622:as a mixed
533:Termination
419:ciclosporin
350:Cyanophycin
335:cyanotoxins
313:Indigoidine
278:Ciclosporin
251:Cytostatics
240:precursors
216:Teixobactin
191:Actinomycin
186:Antibiotics
169:cytostatics
165:antibiotics
134:thiazolines
122:halogenated
96:amino acids
68:, the term
58:nudibranchs
1643:Categories
950:"HC-toxin"
906:References
890:Epothilone
821:-attached
777:Processing
743:hydrolyzes
657:methylated
653:formylated
643:pantethine
549:C-terminus
545:N-terminus
523:Elongation
513:Initiation
446:propionate
434:fatty acid
430:polyketide
415:eukaryotes
331:Nodularins
291:Pyoverdine
261:Fabclavine
256:Epothilone
238:Antibiotic
226:Gramicidin
221:Tyrocidine
211:Vancomycin
206:Daptomycin
196:Bacitracin
130:oxazolines
98:including
835:substrate
787:acylation
702:threonine
684:thioester
631:anhydride
537:Releasing
527:Extending
497:June 2019
489:talk page
266:Bleomycin
81:ribosomes
66:ribosomes
1669:Peptides
1631:17913739
1588:11851476
1559:12828367
1519:28526268
1478:21558170
1429:28633438
1380:19228942
1321:20964365
1272:20845982
1223:30673909
1174:24927540
1112:29014161
1104:16895337
1069:25266991
1026:36754751
1018:10875335
982:16839576
895:Esterase
884:See also
876:reaction
815:acyl-CoA
766:aldehyde
755:lactones
706:cysteine
543:(Order:
517:Starting
483:30673909
308:Pigments
179:Examples
161:pigments
118:acylated
50:bacteria
1654:Enzymes
1622:2238963
1469:3125756
1420:5860034
1371:2645347
1348:Bibcode
1312:2982891
1263:2974439
1214:6460464
1165:4078802
1142:Bibcode
1061:1560782
962:Bibcode
923:(ed.).
799:operons
770:alcohol
762:reduces
747:lactams
562:Domains
456:Modules
442:acetate
403:enzymes
150:trimers
138:serines
39:peptide
1629:
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1102:
1067:
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1024:
1016:
980:
931:
921:Ding K
854:isomer
842:codons
751:esters
698:serine
639:serine
481:
407:operon
320:Toxins
171:, and
146:dimers
89:cyclic
62:inside
1108:S2CID
1065:S2CID
1022:S2CID
793:, or
704:, or
677:amide
633:with
595:NMT:
337:from
159:, or
124:, or
54:fungi
48:like
1627:PMID
1584:PMID
1555:PMID
1515:PMID
1501:1865
1474:PMID
1425:PMID
1376:PMID
1317:PMID
1268:PMID
1219:PMID
1170:PMID
1100:PMID
1057:PMID
1014:PMID
978:PMID
929:ISBN
823:acyl
718:and
680:bond
624:acyl
479:PMID
432:and
424:The
379:Mali
377:pv.
132:and
52:and
1617:PMC
1609:doi
1576:doi
1547:doi
1505:doi
1464:PMC
1456:doi
1415:PMC
1407:doi
1366:PMC
1356:doi
1344:106
1307:PMC
1299:doi
1258:PMC
1250:doi
1209:PMC
1201:doi
1160:PMC
1150:doi
1138:111
1092:doi
1088:106
1049:doi
1006:doi
970:doi
801:or
768:or
635:AMP
620:ATP
547:to
535:or
525:or
515:or
444:or
413:in
327:and
148:or
35:NRP
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110:N
105:N
100:D
33:(
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