Riordan, J. F. The role of metals in enzyme activity. Ann. Clin. Lab. Sci. 7, 119–129 (1977).

CAS  PubMed  Google Scholar 

Ragsdale, S. W. Metals and their scaffolds to promote difficult enzymatic reactions. Chem. Rev. 106, 3317–3337 (2006).

Article  CAS  PubMed  Google Scholar 

Nicolet, Y. Structure–function relationships of radical SAM enzymes. Nat. Catal. 3, 337–350 (2020).

Article  CAS  Google Scholar 

Broderick, J. B., Broderick, W. E. & Hoffman, B. M. Radical SAM enzymes: nature’s choice for radical reactions. FEBS Lett. 597, 92–101 (2023).

Article  CAS  PubMed  Google Scholar 

Imlay, J. A. Iron-sulphur clusters and the problem with oxygen. Mol. Microbiol. 59, 1073–1082 (2006).

Article  PubMed  Google Scholar 

Grell, T. A. J., Goldman, P. J. & Drennan, C. L. SPASM and twitch domains in S-adenosylmethionine (SAM) radical enzymes. J. Biol. Chem. 290, 3964–3971 (2015).

Article  CAS  PubMed  Google Scholar 

Mendauletova, A., Kostenko, A., Lien, Y. & Latham, J. How a subfamily of radical S-adenosylmethionine enzymes became a mainstay of ribosomally synthesized and post-translationally modified peptide discovery. ACS Bio. Med. Chem. Au. 2, 53–59 (2022).

Article  CAS  PubMed  Google Scholar 

Guo, Q. & Morinaka, B. I. Accessing and exploring the unusual chemistry by radical SAM-RiPP enzymes. Curr. Opin Chem. Biol. 81, 102483 (2024).

Article  CAS  PubMed  Google Scholar 

Clark, K. A., Bushin, L. B. & Seyedsayamdost, M. R. RaS-RiPPs in Streptococci and the human microbiome. ACS Bio. Med. Chem. Au. 2, 328–339 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mahanta, N., Hudson, G. A. & Mitchell, D. A. Radical S-adenosylmethionine enzymes involved in RiPP biosynthesis. Biochemistry 56, 5229–5244 (2017).

Benjdia, A. & Berteau, O. Radical SAM enzymes and ribosomally‐synthesized and post‐translationally modified peptides: a growing importance in the microbiomes. Front. Chem. 9, 678068 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hooper, N. M. Families of zinc metalloproteases. FEBS Lett. 354, 1–6 (1994).

Article  CAS  PubMed  Google Scholar 

Lipscomb, W. N. & Sträter, N. Recent advances in zinc enzymology. Chem. Rev. 96, 2375–2434 (1996).

Article  CAS  PubMed  Google Scholar 

Spyroulias, G. A., Galanis, A. S., Pairas, G., Manessi-Zoupa, E. & Cordopatis, P. Structural features of angiotensin-I converting enzyme catalytic sites: conformational studies in solution, homology models and comparison with other zinc metallopeptidases. Curr. Top. Med. Chem. 4, 403–429 (2004).

Article  CAS  PubMed  Google Scholar 

Matthews, B. W., Jansonius, J. N., Colman, P. M., Schoenborn, B. P. & Dupourque, D. Three-dimensional structure of thermolysin. Nat. New Biol. 238, 37–41 (1972).

Article  CAS  PubMed  Google Scholar 

Gao, S.-S., Naowarojna, N., Cheng, R., Liu, X. & Liu, P. Recent examples of α-ketoglutarate-dependent mononuclear non-haem iron enzymes in natural product biosyntheses. Nat. Prod. Rep. 35, 792–837 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Loenarz, C. & Schofield, C. J. Expanding chemical biology of 2-oxoglutarate oxygenases. Nat. Chem. Biol. 4, 152–156 (2008).

Article  CAS  PubMed  Google Scholar 

Hausinger, R. P. FeII/alpha-ketoglutarate-dependent hydroxylases and related enzymes. Crit. Rev. Biochem. Mol. Biol. 39, 21–68 (2004).

Article  CAS  PubMed  Google Scholar 

Schaeffer, R. D., Kinch, L. N., Liao, Y. & Grishin, N. V. Classification of proteins with shared motifs and internal repeats in the ECOD database. Protein Sci. 25, 1188–1203 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aik, W., McDonough, M. A., Thalhammer, A., Chowdhury, R. & Schofield, C. J. Role of the jelly-roll fold in substrate binding by 2-oxoglutarate oxygenases. Curr. Opin. Struct. Biol. 22, 691–700 (2012).

Article  CAS  PubMed  Google Scholar 

Clifton, I. J. et al. Structural studies on 2-oxoglutarate oxygenases and related double-stranded beta-helix fold proteins. J. Inorg. Biochem. 100, 644–669 (2006).

Article  CAS  PubMed  Google Scholar 

Martinez, S. & Hausinger, R. P. Catalytic mechanisms of Fe(II)- and 2-oxoglutarate-dependent oxygenases. J. Biol. Chem. 290, 20702–20711 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sugiyama, R. et al. The biosynthetic landscape of triceptides reveals radical SAM enzymes that catalyze cyclophane formation on Tyr- and His-containing motifs. J. Am. Chem. Soc. https://doi.org/10.1021/jacs.2c00521 (2022).

Article  PubMed  Google Scholar 

Clark, K. A. & Seyedsayamdost, M. R. Bioinformatic atlas of radical SAM enzyme-modified RiPP natural products reveals an isoleucine–tryptophan crosslink. J. Am. Chem. Soc. 144, 17876–17888 (2022).

Article  CAS  PubMed  Google Scholar 

Freeman, M. F. et al. Metagenome mining reveals polytheonamides as posttranslationally modified ribosomal peptides. Science 338, 387–390 (2012).

Article  CAS  PubMed  Google Scholar 

Haft, D. H., Selengut, J. D. & White, O. The TIGRFAMs database of protein families. Nucleic Acids Res. 31, 371–373 (2003).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nguyen, T. Q. N. et al. Post-translational formation of strained cyclophanes in bacteria. Nat. Chem. 12, 1042–1053 (2020).

Article  CAS  PubMed  Google Scholar 

Phan, C.-S. & Morinaka, B. I. A prevalent group of actinobacterial radical SAM/SPASM maturases involved in triceptide biosynthesis. ACS Chem. Biol. 17, 3284–3289 (2022).

Article  CAS  PubMed  Google Scholar 

Phan, C.-S. & Morinaka, B. I. Bacterial cyclophane-containing RiPPs from radical SAM enzymes. Nat. Prod. Rep. 41, 708–720 (2024).

Article  CAS  PubMed  Google Scholar 

Suarez, A. F. L. et al. Functional and promiscuity studies of three-residue cyclophane forming enzymes show nonnative C–C cross-linked products and leader-dependent cyclization. ACS Chem. Biol. 19, 774–783 (2024).

Article  CAS  PubMed  Google Scholar 

Phan, C.-S. et al. Substrate promiscuity of the triceptide maturase XncB leads to incorporation of various amino acids and detection of oxygenated products. ACS Chem. Biol. 19, 855–860 (2024).

Article  CAS  PubMed  Google Scholar 

Purushothaman, M. et al. The triceptide maturase OscB catalyzes uniform cyclophane topology and accepts diverse Gly-rich precursor peptides. ACS Chem. Biol. 19, 1229–1236 (2024).

Article  CAS  PubMed