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Acyltransferase that catalyses the condensation of polyketide and peptide moieties of goadvionin hybrid lipopeptides

Nature Chemistry volume 12, pages 869–877 (2020)Cite this article

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Abstract

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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Fig. 1: Goadvionin biosynthesis gene cluster.
Fig. 2: Characterization of products biosynthesized by the gdv cluster.
Fig. 3: Proposed goadvionin biosynthesis pathway.
Fig. 4: Chemical structures of goadvionins and goadpeptins.
Fig. 5: In vitro reconstitution of acyl transfer catalysed by GdvG.
Fig. 6: Putative secondary metabolite biosynthesis gene clusters containing gdvG homologues are widely distributed in microorganism genomes.

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Data availability

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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Acknowledgements

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.

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Author notes

  1. These authors contributed equally: Ryosuke Kozakai, Takuto Ono.

Authors and Affiliations

  1. Graduate School of Agricultural and Life Sciences, Department of Biotechnology, The University of Tokyo, Tokyo, Japan

    Ryosuke Kozakai, Takuto Ono, Yohei Katsuyama, Yoshinori Sugai, Taro Ozaki, Kazuya Teramoto, Shumpei Asamizu & Hiroyasu Onaka

  2. Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

    Shotaro Hoshino & Ikuro Abe

  3. Koichi Tanaka Mass Spectrometry Research Laboratory Shimadzu Corporation, Kyoto, Japan

    Hidenori Takahashi, Kanae Teramoto & Koichi Tanaka

  4. Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, Japan

    Yohei Katsuyama, Kazuya Teramoto, Ikuro Abe, Shumpei Asamizu & Hiroyasu Onaka

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  1. Ryosuke Kozakai
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Contributions

R.K. and Y.K. performed in vitro assays. T. Ozaki, T. Ono, S.A. and H.O. performed genome mining and bioinformatic analyses. S.H., H.T., Y.S., T. Ono, Kazuya Teramoto, Kanae Teramoto, Koichi Tanaka and I.A. determined chemical structures. R.K., S.H., H.T., Y.K., S.A., Koichi Tanaka and H.O. analysed the data. S.H., Y.K., and H.O. wrote the paper.

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Correspondence to Hiroyasu Onaka.

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Supplementary Figs. 1–56, Methods and Tables 1–16.

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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

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