Adhikari A., Teijaro C. N., Townsend C. A. & Shen B. in Comprehensive Natural Products III (eds Liu, H.-W. & Begley, T. P.) 365–414 (Elsevier, 2020).

Adhikari, A., Shen, B. & Rader, C. Challenges and opportunities to develop enediyne natural products as payloads for antibody-drug conjugates. Antib. Ther. 4, 1–15 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Maeda, H. SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy. Adv. Drug Deliv. Rev. 46, 169–185 (2001).

Article  CAS  PubMed  Google Scholar 

Konishi, M. et al. Dynemicin A, a novel antibiotic with the anthraquinone and 1,5-diyn-3-ene subunit. J. Antibiot. 42, 1449–1452 (1989).

Article  CAS  Google Scholar 

Davies, J. et al. Uncialamycin, a new enediyne antibiotic. Org. Lett. 7, 5233–5236 (2005).

Article  CAS  PubMed  Google Scholar 

Yan, X. et al. Strain prioritization and genome mining for enediyne natural products. mBio 7, e02104–e02116 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nicolaou, K. C. et al. Uncialamycin-based antibody–drug conjugates: unique enediyne ADCs exhibiting bystander killing effect. Proc. Natl Acad. Sci. USA 118, e2107042118 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Low, Z. J. et al. Sungeidines from a non-canonical enediyne biosynthetic pathway. J. Am. Chem. Soc. 142, 1673–1679 (2020).

Article  CAS  PubMed  Google Scholar 

Steele, A. D. et al. Application of a biocatalytic strategy for the preparation of tiancimycin-based antibody–drug conjugates revealing key insights into structure–activity relationships. J. Med. Chem. 66, 1562–1573 (2023).

Article  CAS  PubMed  Google Scholar 

Igarashi, M. et al. Sealutomicins, new enediyne antibiotics from the deep-sea actinomycete Nonomuraea sp. MM565M-173N2. J. Antibiot. 74, 291–299 (2021).

Article  CAS  Google Scholar 

Gui, C. et al. Intramolecular C–C bond formation links anthraquinone and enediyne scaffolds in tiancimycin biosynthesis. J. Am. Chem. Soc. 144, 20452–20462 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yan, X. et al. Comparative studies of the biosynthetic gene clusters for anthraquinone-fused enediynes shedding light into the tailoring steps of tiancimycin biosynthesis. Org. Lett. 20, 5918–5921 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Machovina, M. M., Usselman, R. J. & DuBois, J. L. Monooxygenase substrates mimic flavin to catalyze cofactorless oxygenations. J. Biol. Chem. 291, 17816–17828 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Thierbach, S. et al. Substrate-assisted O2 activation in a cofactor-independent dioxygenase. Chem. Biol. 21, 217–225 (2014).

Article  CAS  PubMed  Google Scholar 

Hernández-Ortega, A. et al. Catalytic mechanism of cofactor-free dioxygenases and how they circumvent spin-forbidden oxygenation of their substrates. J. Am. Chem. Soc. 137, 7474–7487 (2015).

Article  PubMed  Google Scholar 

Machovina, M. M., Ellis, E. S., Carney, T. J., Brushett, F. R. & DuBois, J. L. How a cofactor-free protein environment lowers the barrier to O2 reactivity. J. Biol. Chem. 294, 3661–3669 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Steiner, R. A., Janssen, H. J., Roversi, P., Oakley, A. J. & Fetzner, S. Structural basis for cofactor-independent dioxygenation of N-heteroaromatic compounds at the α/β-hydrolase fold. Proc. Natl Acad. Sci. USA 107, 657–662 (2010).

Article  CAS  PubMed  Google Scholar 

Jansson, A. et al. Aclacinomycin 10-hydroxylase is a novel substrate-assisted hydroxylase requiring S-adenosyl-l-methionine as cofactor. J. Biol. Chem. 280, 3636–3644 (2005).

Article  CAS  PubMed  Google Scholar 

Fetzner, S. & Steiner, R. A. Cofactor-independent oxidases and oxygenases. Appl. Microbiol. Biotechnol. 86, 791–804 (2010).

Article  CAS  PubMed  Google Scholar 

Matthews, J. C., Hori, K. & Cormier, M. J. Substrate and substrate analog binding properties of Renilla luciferase. Biochemistry 16, 5217–5220 (1977).

Article  CAS  PubMed  Google Scholar 

Sarma, A. D. & Tipton, P. A. Evidence for urate hydroperoxide as an intermediate in the urate oxidase reaction. J. Am. Chem. Soc. 122, 11252–11253 (2000).

Article  CAS  Google Scholar 

Sciara, G. et al. The structure of ActVA-Orf6, a novel type of monooxygenase involved in actinorhodin biosynthesis. EMBO J. 22, 205–215 (2003).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Widboom, P. F., Fielding, E. N., Liu, Y. & Bruner, S. D. Structural basis for cofactor-independent dioxygenation in vancomycin biosynthesis. Nature 447, 342–345 (2007).

Article  CAS  PubMed  Google Scholar 

Siitonen, V., Blauenburg, B., Kallio, P., Mäntsälä, P. & Metsä-Ketelä, M. Discovery of a two-component monooxygenase SnoaW/SnoaL2 involved in nogalamycin biosynthesis. Chem. Biol. 19, 638–646 (2012).

Article  CAS  PubMed  Google Scholar 

Shen, B. & Hutchinson, C. R. Tetracenomycin F1 monooxygenase: oxidation of a naphthacenone to a naphthacenequinone in the biosynthesis of tetracenomycin C in Streptomyces glaucescens. Biochemistry 32, 6656–6663 (1993).

Article  CAS  PubMed  Google Scholar 

Tokiwa, Y. et al. Biosynthesis of dynemicin A, a 3-ene-1,5-diyne antitumor antibiotic. J. Am. Chem. Soc. 114, 4107–4110 (1992).

Article  CAS  Google Scholar 

Nicolaou, K. C. et al. Total synthesis and biological evaluation of tiancimycins A and B, yangpumicin A, and related anthraquinone-fused enediyne antitumor antibiotics. J. Am. Chem. Soc. 142, 2549–2561 (2020).

Article  CAS  PubMed  Google Scholar 

Bar-Even, A. et al. The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters. Biochemistry 50, 4402–4410 (2011).

Article  CAS  PubMed  Google Scholar 

Marsh, E. N. G. & Waugh, M. W. Aldehyde decarbonylases: enigmatic enzymes of hydrocarbon biosynthesis. ACS Catal. 3, 2515–2521 (2013).

Article  CAS  Google Scholar 

Qiu, Y. et al. An insect-specific P450 oxidative decarbonylase for cuticular hydrocarbon biosynthesis. Proc. Natl Acad. Sci. USA 109, 14858–14863 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schirmer, A., Rude, M. A., Li, X., Popova, E. & del Cardayre, S. B. Microbial biosynthesis of alkanes. Science 329, 559–562 (2010).

Article  CAS  PubMed  Google Scholar 

Warui, D. M. et al. Detection of formate, rather than carbon monoxide, as the stoichiometric coproduct in conversion of fatty aldehydes to alkanes by a cyanobacterial aldehyde decarbonylase. J. Am. Chem. Soc. 133, 3316–3319 (2011).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schneider-Belhaddad, F. & Kolattukudy, P. Solubilization, partial purification, and characterization of a fatty aldehyde decarbonylase from a higher plant, Pisum sativum. Arch. Biochem. Biophys. 377, 341–349 (2000).

Article  CAS  PubMed  Google Scholar 

Yoshimoto, F. K. & Guengerich, F. P. Mechanism of the third oxidative step in the conversion of androgens to estrogens by cytochrome P450 19A1 steroid aromatase. J. Am. Chem. Soc. 136, 15016–15025 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

He, H.-Y. & Ryan, K. S. Glycine-derived nitronates bifurcate to O-methylation or denitrification in bacteria. Nat. Chem. 13, 599–606 (2021).

Article  CAS  PubMed  Google Scholar 

Jonnalagadda, R. et al. Biochemical and crystallographic investigations into isonitrile formation by a nonheme iron-dependent oxidase/decarboxylase. J. Biol. Chem. 296, 100231 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, Z. et al. Enzyme-catalyzed inverse-electron demand Diels–Alder reaction in the biosynthesis of antifungal ilicicolin H. J. Am. Chem. Soc. 141, 5659–5663 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Townsend, C. A. New reactions in clavulanic acid biosynthesis. Curr. Opin. Chem. Biol. 6, 583–589 (2002).