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Abstract

The past decade has seen impressive advances in understanding the biosynthesis of ribosomally synthesized and posttranslationally modified peptides (RiPPs). One of the most common modifications found in these natural products is macrocyclization, a strategy also used by medicinal chemists to improve metabolic stability and target affinity and specificity. Another tool of the peptide chemist, modification of the amides in a peptide backbone, has also been observed in RiPPs. This review discusses the molecular mechanisms of biosynthesis of a subset of macrocyclic RiPP families, chosen because of the unusual biochemistry involved: the five classes of lanthipeptides (thioether cyclization by Michael-type addition), sactipeptides and ranthipeptides (thioether cyclization by radical chemistry), thiopeptides (cyclization by [4+2] cycloaddition), and streptide (cyclization by radical C–C bond formation). In addition, the mechanisms of backbone amide methylation, backbone epimerization, and backbone thioamide formation are discussed, as well as an unusual route to small molecules by posttranslational modification.

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2022-06-21
2024-10-13
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Literature Cited

  1. 1.
    Montalbán-López M, Scott TA, Ramesh S, Rahman IR, van Heel AJ et al. 2021. New developments in RiPP discovery, enzymology and engineering. Nat. Prod. Rep. 138:130–239
    [Google Scholar]
  2. 2.
    Ortega MA, Hao Y, Zhang Q, Walker MC, van der Donk WA, Nair SK. 2015. Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB. Nature 517:509–12
    [Google Scholar]
  3. 3.
    Koehnke J, Mann G, Bent AF, Ludewig H, Shirran S et al. 2015. Structural analysis of leader peptide binding enables leader-free cyanobactin processing. Nat. Chem. Biol. 11:558–63
    [Google Scholar]
  4. 4.
    Evans RL 3rd, Latham JA, Xia Y, Klinman JP, Wilmot CM. 2017. Nuclear magnetic resonance structure and binding studies of PqqD, a chaperone required in the biosynthesis of the bacterial dehydrogenase cofactor pyrroloquinoline quinone. Biochemistry 56:2735–46
    [Google Scholar]
  5. 5.
    Grove TL, Himes PM, Hwang S, Yumerefendi H, Bonanno JB et al. 2017. Structural insights into thioether bond formation in the biosynthesis of sactipeptides. J. Am. Chem. Soc. 139:11734–44
    [Google Scholar]
  6. 6.
    Chekan JR, Ongpipattanakul C, Nair SK. 2019. Steric complementarity directs sequence promiscuous leader binding in RiPP biosynthesis. PNAS 116:24049–55
    [Google Scholar]
  7. 7.
    Burkhart BJ, Hudson GA, Dunbar KL, Mitchell DA. 2015. A prevalent peptide-binding domain guides ribosomal natural product biosynthesis. Nat. Chem. Biol. 11:564–70
    [Google Scholar]
  8. 8.
    Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS et al. 2013. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat. Prod. Rep. 30:108–60
    [Google Scholar]
  9. 9.
    Cao L, Do T, Link AJ. 2021. Mechanisms of action of ribosomally synthesized and posttranslationally modified peptides (RiPPs). J. Ind. Microbiol. Biotechnol. 48:kuab005
    [Google Scholar]
  10. 10.
    Schnell N, Entian KD, Schneider U, Götz F, Zahner H et al. 1988. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings. Nature 333:276–78
    [Google Scholar]
  11. 11.
    Li YM, Milne JC, Madison LL, Kolter R, Walsh CT. 1996. From peptide precursors to oxazole and thiazole-containing peptide antibiotics: microcin B17 synthase. Science 274:1188–93
    [Google Scholar]
  12. 12.
    Smits THM, Duffy B, Blom J, Ishimaru CA, Stockwell VO. 2019. Pantocin A, a peptide-derived antibiotic involved in biological control by plant-associated Pantoea species. Arch. Microbiol. 201:713–22
    [Google Scholar]
  13. 13.
    Ayikpoe R, Govindarajan V, Latham JA. 2019. Occurrence, function, and biosynthesis of mycofactocin. Appl. Microbiol. Biotechnol. 103:2903–12
    [Google Scholar]
  14. 14.
    Ting CP, Funk MA, Halaby SL, Zhang Z, Gonen T, van der Donk WA. 2019. Use of a scaffold peptide in the biosynthesis of amino acid–derived natural products. Science 365:280–84
    [Google Scholar]
  15. 15.
    Zhu W, Klinman JP. 2020. Biogenesis of the peptide-derived redox cofactor pyrroloquinoline quinone. Curr. Opin. Chem. Biol. 59:93–103
    [Google Scholar]
  16. 16.
    Tang W, Jiménez-Osés G, Houk KN, van der Donk WA. 2015. Substrate control in stereoselective lanthionine biosynthesis. Nat. Chem. 7:57–64
    [Google Scholar]
  17. 17.
    Tang W, van der Donk WA. 2013. The sequence of the enterococcal cytolysin imparts unusual lanthionine stereochemistry. Nat. Chem. Biol. 9:157–59
    [Google Scholar]
  18. 18.
    Repka LM, Chekan JR, Nair SK, van der Donk WA. 2017. Mechanistic understanding of lanthipeptide biosynthetic enzymes. Chem. Rev. 117:5457–520
    [Google Scholar]
  19. 19.
    Ortiz-López FJ, Carretero-Molina D, Sánchez-Hidalgo M, Martín J, González I et al. 2020. Cacaoidin, first member of the new lanthidin RiPP family. Angew. Chem. Int. Ed. 59:12654–58
    [Google Scholar]
  20. 20.
    Xu M, Zhang F, Cheng Z, Bashiri G, Wang J et al. 2020. Functional genome mining reveals a class V lanthipeptide containing a d-amino acid introduced by an F420H2-dependent reductase. Angew. Chem. Int. Ed. 59:18029–35
    [Google Scholar]
  21. 21.
    Kloosterman AM, Cimermancic P, Elsayed SS, Du C, Hadjithomas M et al. 2020. Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lanthipeptides. PLOS Biol 18:e3001026
    [Google Scholar]
  22. 22.
    Li B, Yu JP, Brunzelle JS, Moll GN, van der Donk WA, Nair SK. 2006. Structure and mechanism of the lantibiotic cyclase involved in nisin biosynthesis. Science 311:1464–67
    [Google Scholar]
  23. 23.
    Dong SH, Tang W, Lukk T, Yu Y, Nair SK, van der Donk WA. 2015. The enterococcal cytolysin synthetase has an unanticipated lipid kinase fold. eLife 4:e07607
    [Google Scholar]
  24. 24.
    Zhang Q, Yu Y, Velásquez JE, van der Donk WA. 2012. Evolution of lanthipeptide synthetases. PNAS 109:18361–66
    [Google Scholar]
  25. 25.
    Le T, van der Donk WA. 2021. Mechanisms and evolution of diversity-generating RiPP biosynthesis. Trends Chem 3:266–78
    [Google Scholar]
  26. 26.
    Ortega MA, Hao Y, Walker MC, Donadio S, Sosio M et al. 2016. Structure and tRNA specificity of MibB, a lantibiotic dehydratase from Actinobacteria involved in NAI-107 biosynthesis. Cell Chem. Biol. 23:370–80
    [Google Scholar]
  27. 27.
    Bothwell IR, Caetano T, Sarksian R, Mendo S, van der Donk WA. 2021. Structural analysis of class I lanthipeptides from Pedobacter lusitanus NL19 reveals an unusual ring pattern. ACS Chem. Biol. 16:1019–29
    [Google Scholar]
  28. 28.
    Garg N, Salazar-Ocampo LM, van der Donk WA. 2013. In vitro activity of the nisin dehydratase NisB. PNAS 110:7258–63
    [Google Scholar]
  29. 29.
    Repka LM, Hetrick KJ, Chee SH, van der Donk WA. 2018. Characterization of leader peptide binding during catalysis by the nisin dehydratase NisB. J. Am. Chem. Soc. 140:4200–3
    [Google Scholar]
  30. 30.
    Bothwell IR, Cogan DP, Kim T, Reinhardt CJ, van der Donk WA, Nair SK. 2019. Characterization of glutamyl-tRNA-dependent dehydratases using nonreactive substrate mimics. PNAS 116:17245–50
    [Google Scholar]
  31. 31.
    Hudson GA, Zhang Z, Tietz JI, Mitchell DA, van der Donk WA. 2015. In vitro biosynthesis of the core scaffold of the thiopeptide thiomuracin. J. Am. Chem. Soc. 137:16012–15
    [Google Scholar]
  32. 32.
    Ozaki T, Kurokawa Y, Hayashi S, Oku N, Asamizu S et al. 2016. Insights into the biosynthesis of dehydroalanines in goadsporin. ChemBioChem 17:218–23
    [Google Scholar]
  33. 33.
    Mohr KI, Volz C, Jansen R, Wray V, Hoffmann J et al. 2015. Pinensins: the first antifungal lantibiotics. Angew. Chem. Int. Ed. 54:11254–58
    [Google Scholar]
  34. 34.
    Thibodeaux CJ, Ha T, van der Donk WA. 2014. A price to pay for relaxed substrate specificity: a comparative kinetic analysis of the class II lanthipeptide synthetases ProcM and HalM2. J. Am. Chem. Soc. 136:17513–29
    [Google Scholar]
  35. 35.
    Le T, Jeanne Dit Fouque K, Santos-Fernandez M, Navo CD, Jiménez-Osés G et al. 2021. Substrate sequence controls regioselectivity of lanthionine formation by ProcM. J. Am. Chem. Soc. 143:18733–43
    [Google Scholar]
  36. 36.
    Goto Y, Li B, Claesen J, Shi Y, Bibb MJ, van der Donk WA. 2010. Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights. PLOS Biol 8:e1000339
    [Google Scholar]
  37. 37.
    Wang H, van der Donk WA. 2012. Biosynthesis of the class III lantipeptide catenulipeptin. ACS Chem. Biol. 7:1529–35
    [Google Scholar]
  38. 38.
    Müller WM, Schmiederer T, Ensle P, Süssmuth RD. 2010. In vitro biosynthesis of the prepeptide of type-III lantibiotic labyrinthopeptin A2 including formation of a C–C bond as a post-translational modification. Angew. Chem. Int. Ed. 49:2436–40
    [Google Scholar]
  39. 39.
    Meindl K, Schmiederer T, Schneider K, Reicke A, Butz D et al. 2010. Labyrinthopeptins: a new class of carbacyclic lantibiotics. Angew. Chem. Int. Ed. 49:1151–54
    [Google Scholar]
  40. 40.
    Jungmann NA, Krawczyk B, Tietzmann M, Ensle P, Süssmuth RD. 2014. Dissecting reactions of nonlinear precursor peptide processing of the class III lanthipeptide curvopeptin. J. Am. Chem. Soc. 136:15222–28
    [Google Scholar]
  41. 41.
    Goto Y, Ökesli A, van der Donk WA. 2011. Mechanistic studies of Ser/Thr dehydration catalyzed by a member of the LanL lanthionine synthetase family. Biochemistry 50:891–98
    [Google Scholar]
  42. 42.
    Zhu Y, Li H, Long C, Hu L, Xu H et al. 2007. Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase. Mol. Cell 28:899–913
    [Google Scholar]
  43. 43.
    Hegemann JD, van der Donk WA. 2018. Investigation of substrate recognition and biosynthesis in class IV lanthipeptide systems. J. Am. Chem. Soc. 140:5743–54
    [Google Scholar]
  44. 44.
    Hegemann JD, Shi L, Gross ML, van der Donk WA. 2019. Mechanistic studies of the kinase domains of Class IV lanthipeptide synthetases. ACS Chem. Biol. 14:1583–92
    [Google Scholar]
  45. 45.
    Qiu Y, Liu J, Li Y, Xue Y, Liu W. 2021. Formation of an aminovinyl-cysteine residue in thioviridamides occurs through a path independent of known lanthionine synthetase activity. Cell Chem. Biol. 28:675–85.e5
    [Google Scholar]
  46. 46.
    Eyles TH, Vior NM, Lacret R, Truman AW. 2021. Understanding thioamitide biosynthesis using pathway engineering and untargeted metabolomics. Chem. Sci. 12:7138–50
    [Google Scholar]
  47. 47.
    Truman AW. 2016. Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides. Beilstein J. Org. Chem. 12:1250–68
    [Google Scholar]
  48. 48.
    Flühe L, Knappe TA, Gattner MJ, Schäfer A, Burghaus O et al. 2012. The radical SAM enzyme AlbA catalyzes thioether bond formation in subtilosin A. Nat. Chem. Biol. 8:350–57
    [Google Scholar]
  49. 49.
    Flühe L, Burghaus O, Wieckowski BM, Giessen TW, Linne U, Marahiel MA. 2013. Two [4Fe-4S] clusters containing radical SAM enzyme SkfB catalyze thioether bond formation during the maturation of the sporulation killing factor. J. Am. Chem. Soc. 135:959–62
    [Google Scholar]
  50. 50.
    Broderick JB, Duffus BR, Duschene KS, Shepard EM. 2014. Radical S-adenosylmethionine enzymes. Chem. Rev. 114:4229–317
    [Google Scholar]
  51. 51.
    Grell TA, Goldman PJ, Drennan CL. 2015. SPASM and twitch domains in S-adenosylmethionine (SAM) radical enzymes. J. Biol. Chem. 290:3964–71
    [Google Scholar]
  52. 52.
    Benjdia A, Guillot A, Lefranc B, Vaudry H, Leprince J, Berteau O. 2016. Thioether bond formation by SPASM domain radical SAM enzymes: Cα H-atom abstraction in subtilosin A biosynthesis. Chem. Commun. 52:6249–52
    [Google Scholar]
  53. 53.
    Bruender NA, Wilcoxen J, Britt RD, Bandarian V. 2016. Biochemical and spectroscopic characterization of a radical S-adenosyl-l-methionine enzyme involved in the formation of a peptide thioether cross-link. Biochemistry 55:2122–34
    [Google Scholar]
  54. 54.
    Kincannon WM, Bruender NA, Bandarian V. 2018. A radical clock probe uncouples H atom abstraction from thioether cross-link formation by the radical S-adenosyl-l-methionine enzyme SkfB. Biochemistry 57:4816–23
    [Google Scholar]
  55. 55.
    Kawulka K, Sprules T, McKay RT, Mercier P, Diaper CM et al. 2003. Structure of subtilosin A, an antimicrobial peptide from Bacillus subtilis with unusual posttranslational modifications linking cysteine sulfurs to α-carbons of phenylalanine and threonine. J. Am. Chem. Soc. 125:4726–27
    [Google Scholar]
  56. 56.
    Bruender NA, Bandarian V. 2016. SkfB abstracts a hydrogen atom from Cα on SkfA to initiate thioether cross-link formation. Biochemistry 55:4131–34
    [Google Scholar]
  57. 57.
    Grell TAJ, Kincannon WM, Bruender NA, Blaesi EJ, Krebs C et al. 2018. Structural and spectroscopic analyses of the sporulation killing factor biosynthetic enzyme SkfB, a bacterial AdoMet radical sactisynthase. J. Biol. Chem. 293:17349–61
    [Google Scholar]
  58. 58.
    Haft DH, Basu MK. 2011. Biological systems discovery in silico: radical S-adenosylmethionine protein families and their target peptides for posttranslational modification. J. Bacteriol. 193:2745–55
    [Google Scholar]
  59. 59.
    Hudson GA, Burkhart BJ, DiCaprio AJ, Schwalen CJ, Kille B et al. 2019. Bioinformatic mapping of radical S-adenosylmethionine-dependent ribosomally synthesized and post-translationally modified peptides identifies new Cα, Cβ, and Cγ-linked thioether-containing peptides. J. Am. Chem. Soc. 141:8228–38
    [Google Scholar]
  60. 60.
    Nakai T, Ito H, Kobayashi K, Takahashi Y, Hori H et al. 2015. The radical S-adenosyl-l-methionine enzyme QhpD catalyzes sequential formation of intra-protein sulfur-to-methylene carbon thioether bonds. J. Biol. Chem. 290:11144–66
    [Google Scholar]
  61. 61.
    Caruso A, Bushin LB, Clark KA, Martinie RJ, Seyedsayamdost MR. 2019. Radical approach to enzymatic β-thioether bond formation. J. Am. Chem. Soc. 141:990–97
    [Google Scholar]
  62. 62.
    Precord TW, Mahanta N, Mitchell DA. 2019. Reconstitution and substrate specificity of the thioether-forming radical S-adenosylmethionine enzyme in freyrasin biosynthesis. ACS Chem. Biol. 14:1981–89
    [Google Scholar]
  63. 63.
    Reisberg SH, Gao Y, Walker AS, Helfrich EJN, Clardy J, Baran PS. 2020. Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A. Science 367:458–63
    [Google Scholar]
  64. 64.
    Zdouc MM, Alanjary MM, Zarazúa GS, Maffioli SI, Crüsemann M et al. 2021. A biaryl-linked tripeptide from Planomonospora reveals a widespread class of minimal RiPP gene clusters. Cell Chem. Biol. 28:733–39.e4
    [Google Scholar]
  65. 65.
    Schramma KR, Bushin LB, Seyedsayamdost MR. 2015. Structure and biosynthesis of a macrocyclic peptide containing an unprecedented lysine-to-tryptophan crosslink. Nat. Chem. 7:431–37
    [Google Scholar]
  66. 66.
    Schramma KR, Seyedsayamdost MR. 2017. Lysine-tryptophan-crosslinked peptides produced by radical SAM enzymes in pathogenic Streptococci. ACS Chem. Biol. 12:922–27
    [Google Scholar]
  67. 67.
    Bushin LB, Clark KA, Pelczer I, Seyedsayamdost MR. 2018. Charting an unexplored streptococcal biosynthetic landscape reveals a unique peptide cyclization motif. J. Am. Chem. Soc. 140:17674–84
    [Google Scholar]
  68. 68.
    Caruso A, Martinie RJ, Bushin LB, Seyedsayamdost MR. 2019. Macrocyclization via an arginine-tyrosine crosslink broadens the reaction scope of radical S-adenosylmethionine enzymes. J. Am. Chem. Soc. 141:16610–14
    [Google Scholar]
  69. 69.
    Rued BE, Covington BC, Bushin LB, Szewczyk G, Laczkovich I et al. 2021. Quorum sensing in Streptococcus mutans regulates production of tryglysin, a novel RaS-RiPP antimicrobial compound. mBio 12:e02688–20
    [Google Scholar]
  70. 70.
    Imai Y, Meyer KJ, Iinishi A, Favre-Godal Q, Green R et al. 2019. A new antibiotic selectively kills gram-negative pathogens. Nature 593:125–29
    [Google Scholar]
  71. 71.
    Benjdia A, Decamps L, Guillot A, Kubiak X, Ruffie P et al. 2017. Insights into the catalysis of a lysine-tryptophan bond in bacterial peptides by a SPASM domain radical S-adenosylmethionine (SAM) peptide cyclase. J. Biol. Chem. 292:10835–44
    [Google Scholar]
  72. 72.
    Davis KM, Schramma KR, Hansen WA, Bacik JP, Khare SD et al. 2017. Structures of the peptide-modifying radical SAM enzyme SuiB elucidate the basis of substrate recognition. PNAS 114:10420–25
    [Google Scholar]
  73. 73.
    Schramma KR, Forneris CC, Caruso A, Seyedsayamdost MR. 2018. Mechanistic investigations of lysine–tryptophan cross-link formation catalyzed by streptococcal radical S-adenosylmethionine enzymes. Biochemistry 57:461–68
    [Google Scholar]
  74. 74.
    Horitani M, Shisler K, Broderick WE, Hutcheson RU, Duschene KS et al. 2016. Radical SAM catalysis via an organometallic intermediate with an Fe–[5′-C]-deoxyadenosyl bond. Science 352:822–25
    [Google Scholar]
  75. 75.
    Balo AR, Caruso A, Tao L, Tantillo DJ, Seyedsayamdost MR, Britt RD. 2021. Trapping a cross-linked lysine–tryptophan radical in the catalytic cycle of the radical SAM enzyme SuiB. PNAS 118:e2101571118
    [Google Scholar]
  76. 76.
    Hudson GA, Hooper AR, DiCaprio AJ, Sarlah D, Mitchell DA. 2021. Structure prediction and synthesis of pyridine-based macrocyclic peptide natural products. Org. Lett. 23:253–56
    [Google Scholar]
  77. 77.
    Burkhart BJ, Schwalen C, Mann G, Naismith JH, Mitchell DA. 2017. YcaO-dependent posttranslational amide activation: biosynthesis, structure, and function. Chem. Rev. 117:5389–456
    [Google Scholar]
  78. 78.
    Bycroft BW, Gowland MS. 1978. The structures of the highly modified peptide antibiotics micrococcin P1 and P2. J. Chem. Soc. Chem. Commun. 6:256–58
    [Google Scholar]
  79. 79.
    Kelly WL, Pan L, Li C. 2009. Thiostrepton biosynthesis: prototype for a new family of bacteriocins. J. Am. Chem. Soc. 131:4327–34
    [Google Scholar]
  80. 80.
    Wieland Brown LC, Acker MG, Clardy J, Walsh CT, Fischbach MA. 2009. Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin. PNAS 106:2549–53
    [Google Scholar]
  81. 81.
    Morris RP, Leeds JA, Naegeli HU, Oberer L, Memmert K et al. 2009. Ribosomally synthesized thiopeptide antibiotics targeting elongation factor Tu. J. Am. Chem. Soc. 131:5946–55
    [Google Scholar]
  82. 82.
    Liao R, Duan L, Lei C, Pan H, Ding Y et al. 2009. Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. Chem. Biol. 16:141–47
    [Google Scholar]
  83. 83.
    Bowers AA, Walsh CT, Acker MG. 2010. Genetic interception and structural characterization of thiopeptide cyclization precursors from Bacillus cereus. J. Am. Chem. Soc. 132:12182–84
    [Google Scholar]
  84. 84.
    Wever WJ, Bogart JW, Baccile JA, Chan AN, Schroeder FC, Bowers AA. 2015. Chemoenzymatic synthesis of thiazolyl peptide natural products featuring an enzyme-catalyzed formal [4 + 2] cycloaddition. J. Am. Chem. Soc. 137:3494–97
    [Google Scholar]
  85. 85.
    Bogart JW, Kramer NJ, Turlik A, Bleich RM, Catlin DS et al. 2020. Interception of the Bycroft–Gowland intermediate in the enzymatic macrocyclization of thiopeptides. J. Am. Chem. Soc. 142:13170–79
    [Google Scholar]
  86. 86.
    Cogan DP, Hudson GA, Zhang Z, Pogorelov TV, van der Donk WA et al. 2017. Structural insights into enzymatic [4+2] aza-cycloaddition in thiopeptide antibiotic biosynthesis. PNAS 114:12928–33
    [Google Scholar]
  87. 87.
    Zhang Z, Hudson GA, Mahanta N, Tietz JI, van der Donk WA, Mitchell DA. 2016. Biosynthetic timing and substrate specificity for the thiopeptide thiomuracin. J. Am. Chem. Soc. 138:15511–14
    [Google Scholar]
  88. 88.
    Wever WJ, Bogart JW, Bowers AA. 2016. Identification of pyridine synthase recognition sequences allows a modular solid-phase route to thiopeptide variants. J. Am. Chem. Soc. 138:13461–64
    [Google Scholar]
  89. 89.
    Bogart JW, Bowers AA. 2019. Thiopeptide pyridine synthase TbtD catalyzes an intermolecular formal aza-diels-alder reaction. J. Am. Chem. Soc. 141:1842–46
    [Google Scholar]
  90. 90.
    van der Velden NS, Kalin N, Helf MJ, Piel J, Freeman MF, Künzler M. 2017. Autocatalytic backbone N-methylation in a family of ribosomal peptide natural products. Nat. Chem. Biol. 13:833–35
    [Google Scholar]
  91. 91.
    Ramm S, Krawczyk B, Muhlenweg A, Poch A, Mosker E, Süssmuth RD. 2017. A self-sacrificing N-methyltransferase is the precursor of the fungal natural product omphalotin. Angew. Chem. Int. Ed. 56:9994–97
    [Google Scholar]
  92. 92.
    Song H, van der Velden NS, Shiran SL, Bleiziffer P, Zach C et al. 2018. A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds. Sci. Adv. 4:eaat2720
    [Google Scholar]
  93. 93.
    Ongpipattanakul C, Nair SK. 2018. Molecular basis for autocatalytic backbone N-methylation in RiPP natural product biosynthesis. ACS Chem. Biol. 13:2989–99
    [Google Scholar]
  94. 94.
    Naismith JH, Song H, Burton AJ, Shirran SL, Fahrig-Kamarauskaitė J et al. 2021. Engineering of a peptide α-N-methyltransferase to methylate non-proteinogenic amino acids. Angew. Chem. Int. Ed. 60:14319–23
    [Google Scholar]
  95. 95.
    Miller FS, Crone KK, Jensen MR, Shaw S, Harcombe WR et al. 2021. Conformational rearrangements enable iterative backbone N-methylation in RiPP biosynthesis. Nat. Commun. 12:5355
    [Google Scholar]
  96. 96.
    Skaugen M, Nissenmeyer J, Jung G, Stevanovic S, Sletten K et al. 1994. In vivo conversion of l-serine to d-alanine in a ribosomally synthesized polypeptide. J. Biol. Chem. 269:27183–85
    [Google Scholar]
  97. 97.
    Lohans CT, Li JL, Vederas JC. 2014. Structure and biosynthesis of carnolysin, a homologue of enterococcal cytolysin with d-amino acids. J. Am. Chem. Soc. 136:13150–53
    [Google Scholar]
  98. 98.
    Freeman MF, Gurgui C, Helf MJ, Morinaka BI, Uria AR et al. 2012. Metagenome mining reveals polytheonamides as posttranslationally modified ribosomal peptides. Science 338:387–90
    [Google Scholar]
  99. 99.
    Morinaka BI, Vagstad AL, Helf MJ, Gugger M, Kegler C et al. 2014. Radical S-adenosyl methionine epimerases: regioselective introduction of diverse D-amino acid patterns into peptide natural products. Angew. Chem. Int. Ed. 53:8503–7
    [Google Scholar]
  100. 100.
    Vagstad AL, Kuranaga T, Püntener S, Pattabiraman VR, Bode JW, Piel J. 2019. Introduction of d-amino acids in minimalistic peptide substrates by an S-adenosyl-l-methionine radical epimerase. Angew. Chem. Int. Ed. 58:2246–50
    [Google Scholar]
  101. 101.
    Freeman MF, Helf MJ, Bhushan A, Morinaka BI, Piel J. 2017. Seven enzymes create extraordinary molecular complexity in an uncultivated bacterium. Nat. Chem. 9:387–95
    [Google Scholar]
  102. 102.
    Parent A, Benjdia A, Guillot A, Kubiak X, Balty C et al. 2018. Mechanistic investigations of PoyD, a radical S-adenosyl-l-methionine enzyme catalyzing iterative and directional epimerizations in polytheonamide A biosynthesis. J. Am. Chem. Soc. 140:2469–77
    [Google Scholar]
  103. 103.
    Byer AS, Yang H, McDaniel EC, Kathiresan V, Impano S et al. 2018. Paradigm shift for radical S-adenosyl-l-methionine reactions: the organometallic intermediate Ω is central to catalysis. J. Am. Chem. Soc. 140:8634–38
    [Google Scholar]
  104. 104.
    Benjdia A, Guillot A, Ruffie P, Leprince J, Berteau O. 2017. Post-translational modification of ribosomally synthesized peptides by a radical SAM epimerase in Bacillus subtilis. Nat. Chem. 9:698–707
    [Google Scholar]
  105. 105.
    Popp PF, Friebel L, Benjdia A, Guillot A, Berteau O, Mascher T. 2021. The epipeptide biosynthesis locus epeXEPAB is widely distributed in Firmicutes and triggers intrinsic cell envelope stress. Microb. Physiol. 31:306–17
    [Google Scholar]
  106. 106.
    Wagner AF, Frey M, Neugebauer FA, Schafer W, Knappe J. 1992. The free radical in pyruvate formate-lyase is located on glycine-734. PNAS 89:996–1000
    [Google Scholar]
  107. 107.
    Izawa M, Kawasaki T, Hayakawa Y. 2013. Cloning and heterologous expression of the thioviridamide biosynthesis gene cluster from Streptomyces olivoviridis. Appl. Environ. Microbiol. 79:7110–13
    [Google Scholar]
  108. 108.
    Ermler U, Grabarse W, Shima S, Goubeaud M, Thauer RK. 1997. Crystal structure of methyl coenzyme M reductase: the key enzyme of biological methane formation. Science 278:1457–62
    [Google Scholar]
  109. 109.
    Nayak DD, Mahanta N, Mitchell DA, Metcalf WW. 2017. Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea. eLife 6:e29218
    [Google Scholar]
  110. 110.
    Mahanta N, Liu A, Dong S, Nair SK, Mitchell DA. 2018. Enzymatic reconstitution of ribosomal peptide backbone thioamidation. PNAS 115:3030–35
    [Google Scholar]
  111. 111.
    Liu A, Si Y, Dong S-H, Mahanta N, Penkala HN et al. 2021. Functional elucidation of TfuA in peptide backbone thioamidation. Nat. Chem. Biol. 17:585–92
    [Google Scholar]
  112. 112.
    Schwalen CJ, Hudson GA, Kille B, Mitchell DA. 2018. Bioinformatic expansion and discovery of thiopeptide antibiotics. J. Am. Chem. Soc. 140:9494–501
    [Google Scholar]
  113. 113.
    Kjaerulff L, Sikandar A, Zaburannyi N, Adam S, Herrmann J et al. 2017. Thioholgamides: thioamide-containing cytotoxic RiPP natural products. ACS Chem. Biol. 12:2837–41
    [Google Scholar]
  114. 114.
    Santos-Aberturas J, Chandra G, Frattaruolo L, Lacret R, Pham TH et al. 2019. Uncovering the unexplored diversity of thioamidated ribosomal peptides in Actinobacteria using the RiPPER genome mining tool. Nucleic Acids Res 47:4624–37
    [Google Scholar]
  115. 115.
    Daniels PN, Lee H, Splain RA, Ting CP, Zhu L et al. 2022. A biosynthetic pathway to aromatic amines that uses glycyl-tRNA as nitrogen donor. Nat. Chem. 14:7177
    [Google Scholar]
  116. 116.
    Zhang Z, van der Donk WA. 2019. Nonribosomal peptide extension by a peptide amino-acyl tRNA ligase. J. Am. Chem. Soc. 141:19625–33
    [Google Scholar]
  117. 117.
    Jordan PA, Moore BS. 2016. Biosynthetic pathway connects cryptic ribosomally synthesized posttranslationally modified peptide genes with pyrroloquinoline alkaloids. Cell Chem. Biol. 23:1504–14
    [Google Scholar]
  118. 118.
    Sikandar A, Koehnke J. 2019. The role of protein–protein interactions in the biosynthesis of ribosomally synthesized and post-translationally modified peptides. Nat. Prod. Rep. 36:1576–88
    [Google Scholar]
  119. 119.
    DiCaprio AJ, Firouzbakht A, Hudson GA, Mitchell DA. 2019. Enzymatic reconstitution and biosynthetic investigation of the lasso peptide fusilassin. J. Am. Chem. Soc. 141:290–97
    [Google Scholar]
  120. 120.
    Koos JD, Link AJ. 2019. Heterologous and in vitro reconstitution of fuscanodin, a lasso peptide from Thermobifida fusca. J. Am. Chem. Soc. 141:928–35
    [Google Scholar]
  121. 121.
    Kersten RD, Weng JK. 2018. Gene-guided discovery and engineering of branched cyclic peptides in plants. PNAS 115:E10961–69
    [Google Scholar]
  122. 122.
    Chigumba DN, Mydy LS, de Waal F, Li W, Shafiq K et al. 2021. Discovery and biosynthesis of cyclic plant peptides via autocatalytic cyclases. Nat. Chem. Biol. 18:18–28
    [Google Scholar]
  123. 123.
    Morinaka BI, Lakis E, Verest M, Helf MJ, Scalvenzi T et al. 2018. Natural noncanonical protein splicing yields products with diverse β-amino acid residues. Science 359:779–82
    [Google Scholar]
  124. 124.
    Kawulka KE, Sprules T, Diaper CM, Whittal RM, McKay RT et al. 2004. Structure of subtilosin A, a cyclic antimicrobial peptide from Bacillus subtilis with unusual sulfur to α-carbon cross-links: formation and reduction of α-thio-α-amino acid derivatives. Biochemistry 43:3385–95
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-032620-104956
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