Fusions of fatty acids and peptides expand the structural diversity of natural products; however, polyketide/ribosomally synthesized and post-translationally modified peptides (PK/RiPPs) hybrid lipopeptides are relatively rare. Here we report a family of PK/RiPPs called goadvionins, which inhibit the growth of Gram-positive bacteria, and an acyltransferase, GdvG, which catalyses the condensation of the PK and RiPP moieties. Goadvionin comprises a trimethylammonio 32-carbon acyl chain and an eight-residue RiPP with an avionin structure. The positions of six hydroxyl groups and one double bond in the very-long acyl chain were determined by radical-induced dissociation tandem mass spectrometry, which collides radical ion species to generate C–C bond cleavage fragments. GdvG belongs to the Gcn5-related N-acetyltransferase superfamily. Unlike conventional acyltransferases, GdvG transfers a very long acyl chain that is tethered to an acyl carrier protein to the N-terminal amino group of the RiPP moiety. gdvG homologues flanked by PK/fatty acid and RiPP biosynthesis genes are widely distributed in microbial species, suggesting that acyltransferase-catalysed condensation of PKs and RiPPs is a general strategy in biosynthesis of similar lipopeptides.
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All relevant data are included in the manuscript and the Supplementary Information. The nucleotide sequence of the gdv cluster has been deposited in the DDBJ with accession number LC481990.
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This research was supported in part by a grant-in-aid from the IFO, Institute for Fermentation, Osaka (to H.O., S.A. and T. Ozaki), Amano Enzyme (to H.O and S.A), JSPS KAKENHI grant-in-aid for Young Scientists B (no. 26850044 to S.A.), JSPS KAKENHI grant-in-aid for Scientific Research on Innovative Areas (no. JP16H06444) and the JSPS A3 Foresight Program (to H.O., S.A. and Y.K.). We thank D. Du and T. Tsunoda for assistance with the in vitro assays, S. Kawano for assistance with genetic work, D. Asakawa for HAD-MS/MS data analysis, M. Wada and Y. Shimabukuro for HAD-MS/MS development, and Y. Ohnishi and S. Iwamoto for valuable comments on the manuscript.
The authors declare no competing interests.
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Kozakai, R., Ono, T., Hoshino, S. et al. Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides. Nat. Chem. 12, 869–877 (2020). https://doi.org/10.1038/s41557-020-0508-2
Nature Chemical Biology (2022)