Ribosomally Synthesized and Post-translationally Modified Peptide Natural Products: Overview and Recommendations for a Universal Nomenclature

This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.

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References

Shenkarev Z, Nadezhdin K, Lyukmanova E, Sobol V, Skjeldal L, Arseniev A . Divalent cation coordination and mode of membrane interaction in cyclotides: NMR spatial structure of ternary complex Kalata B7/Mn2+/DPC micelle. J Inorg Biochem. 2008; 102(5-6):1246-56. DOI: 10.1016/j.jinorgbio.2008.01.018. View

Frey P, Hegeman A, Ruzicka F . The Radical SAM Superfamily. Crit Rev Biochem Mol Biol. 2008; 43(1):63-88. DOI: 10.1080/10409230701829169. View

Islam M, Shioya K, Nagao J, Nishie M, Jikuya H, Zendo T . Evaluation of essential and variable residues of nukacin ISK-1 by NNK scanning. Mol Microbiol. 2009; 72(6):1438-47. DOI: 10.1111/j.1365-2958.2009.06733.x. View

Tianero M, Donia M, Young T, Schultz P, Schmidt E . Ribosomal route to small-molecule diversity. J Am Chem Soc. 2011; 134(1):418-25. PMC: 3268757. DOI: 10.1021/ja208278k. View

Oman T, Knerr P, Bindman N, Velasquez J, van der Donk W . An engineered lantibiotic synthetase that does not require a leader peptide on its substrate. J Am Chem Soc. 2012; 134(16):6952-5. PMC: 3350211. DOI: 10.1021/ja3017297. View

Otaka T, Kaji A . Mode of action of bottromycin A2. Release of aminoacyl- or peptidyl-tRNA from ribosomes. J Biol Chem. 1976; 251(8):2299-306. View

Martin-Visscher L, Yoganathan S, Sit C, Lohans C, Vederas J . The activity of bacteriocins from Carnobacterium maltaromaticum UAL307 against gram-negative bacteria in combination with EDTA treatment. FEMS Microbiol Lett. 2011; 317(2):152-9. DOI: 10.1111/j.1574-6968.2011.02223.x. View

Vassilevski A, Kozlov S, Grishin E . Molecular diversity of spider venom. Biochemistry (Mosc). 2010; 74(13):1505-34. DOI: 10.1134/s0006297909130069. View

Kodani S, Lodato M, Durrant M, Picart F, Willey J . SapT, a lanthionine-containing peptide involved in aerial hyphae formation in the streptomycetes. Mol Microbiol. 2005; 58(5):1368-80. DOI: 10.1111/j.1365-2958.2005.04921.x. View

10.

Maksimov M, Pelczer I, Link A . Precursor-centric genome-mining approach for lasso peptide discovery. Proc Natl Acad Sci U S A. 2012; 109(38):15223-8. PMC: 3458324. DOI: 10.1073/pnas.1208978109. View

11.

Kaneda M . Studies on bottromycins. I. 1H and 13C NMR assignments of bottromycin A2, the main component of the complex. J Antibiot (Tokyo). 1992; 45(5):792-6. DOI: 10.7164/antibiotics.45.792. View

12.

Walton J, Hallen-Adams H, Luo H . Ribosomal biosynthesis of the cyclic peptide toxins of Amanita mushrooms. Biopolymers. 2010; 94(5):659-64. PMC: 4001729. DOI: 10.1002/bip.21416. View

13.

Okesli A, Cooper L, Fogle E, van der Donk W . Nine post-translational modifications during the biosynthesis of cinnamycin. J Am Chem Soc. 2011; 133(34):13753-60. PMC: 3163434. DOI: 10.1021/ja205783f. View

14.

Saska I, Gillon A, Hatsugai N, Dietzgen R, Hara-Nishimura I, Anderson M . An asparaginyl endopeptidase mediates in vivo protein backbone cyclization. J Biol Chem. 2007; 282(40):29721-8. DOI: 10.1074/jbc.M705185200. View

15.

Wieland Brown L, Acker M, Clardy J, Walsh C, Fischbach M . Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin. Proc Natl Acad Sci U S A. 2009; 106(8):2549-53. PMC: 2650375. DOI: 10.1073/pnas.0900008106. View

16.

Meindl K, Schmiederer T, Schneider K, Reicke A, Butz D, Keller S . Labyrinthopeptins: a new class of carbacyclic lantibiotics. Angew Chem Int Ed Engl. 2010; 49(6):1151-4. DOI: 10.1002/anie.200905773. View

17.

Bierbaum G, Sahl H . Lantibiotics: mode of action, biosynthesis and bioengineering. Curr Pharm Biotechnol. 2009; 10(1):2-18. DOI: 10.2174/138920109787048616. View

18.

Li B, Sher D, Kelly L, Shi Y, Huang K, Knerr P . Catalytic promiscuity in the biosynthesis of cyclic peptide secondary metabolites in planktonic marine cyanobacteria. Proc Natl Acad Sci U S A. 2010; 107(23):10430-5. PMC: 2890784. DOI: 10.1073/pnas.0913677107. View

19.

Solbiati J, Ciaccio M, Farias R, Moreno F, Salomon R . Sequence analysis of the four plasmid genes required to produce the circular peptide antibiotic microcin J25. J Bacteriol. 1999; 181(8):2659-62. PMC: 93700. DOI: 10.1128/JB.181.8.2659-2662.1999. View

20.

Bertram A, Pattenden G . Marine metabolites: metal binding and metal complexes of azole-based cyclic peptides of marine origin. Nat Prod Rep. 2007; 24(1):18-30. DOI: 10.1039/b612600f. View