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Enzyme-catalyzed spiroacetal formation in polyketide antibiotic biosynthesis
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Bilyk, Oksana, Oliveira, Gabriel S., de Angelo, Rafaela M., Almeida, Michell O., Honório, Kathia Maria, Leeper, Finian J., Dias, Marcio Vinicius Bertacine and Leadlay, Peter F. (2022) Enzyme-catalyzed spiroacetal formation in polyketide antibiotic biosynthesis. Journal of the American Chemical Society, 144 (32). pp. 14555-14563. doi:10.1021/jacs.2c03313 ISSN 1520-5126.
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Official URL: https://doi.org/10.1021/jacs.2c03313
Abstract
A key step in the biosynthesis of numerous polyketides is the stereospecific formation of a spiroacetal (spiroketal). We report here that spiroacetal formation in the biosynthesis of the macrocyclic polyketides ossamycin and oligomycin involves catalysis by a novel spiroacetal cyclase. OssO from the ossamycin biosynthetic gene cluster (BGC) is homologous to OlmO, the product of an unannotated gene from the oligomycin BGC. The deletion of olmO abolished oligomycin production and led to the isolation of oligomycin-like metabolites lacking the spiroacetal structure. Purified OlmO catalyzed complete conversion of the major metabolite into oligomycin C. Crystal structures of OssO and OlmO reveal an unusual 10-strand β-barrel. Three conserved polar residues are clustered together in the β-barrel cavity, and site-specific mutation of any of these residues either abolished or substantially diminished OlmO activity, supporting a role for general acid/general base catalysis in spiroacetal formation.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||
| SWORD Depositor: | Library Publications Router | ||||||||
| Journal or Publication Title: | Journal of the American Chemical Society | ||||||||
| Publisher: | American Chemical Society (ACS) | ||||||||
| ISSN: | 1520-5126 | ||||||||
| Official Date: | 17 August 2022 | ||||||||
| Dates: |
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| Volume: | 144 | ||||||||
| Number: | 32 | ||||||||
| Page Range: | pp. 14555-14563 | ||||||||
| DOI: | 10.1021/jacs.2c03313 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| Copyright Holders: | Copyright © 2022 American Chemical Society |
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