| Autor: |
Oksana Bilyk, Finian Leeper, Marcio Vinicius Bertacine Dias, Peter Leadlay |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.26434/chemrxiv-2022-h4v7z |
| Popis: |
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 BCG. Deletion of olmO abolished oligomycin production and led to the isolation of oligomycin-like metabolites lacking the spiroacetal structure. Purified OlmO catalysed complete conversion of the major metabolite into oligomycin C. Crystal structures of OssO and OlmO reveal an unusual 10-strand -barrel. Three conserved polar residues are clustered together in the -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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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