3 years ago

Toblerols, Cyclopropanol-Containing Modulators of Methylobacterial Antibiosis Generated by an Unusual Polyketide Synthase

Miriam Bortfeld-Miller, Jörn Piel, Julia Anne Vorholt, Reiko Ueoka, Brandon Isamu Morinaka
Trans-AT polyketide synthases (PKSs) are biosynthetically versatile enzymes that generate bioactive polyketides of high structural diversity. In this study, we detected in the genome of several bacteria a cryptic, unusual trans-AT PKS gene cluster that eluded automated PKS prediction. Genomic mining of one of these strains, the model methylotroph Methylobacterium extorquens AM1, revealed epoxide-cyclopropanol-containing polyketides named toblerols. The stereochemistry was determined by NMR, chemical derivatization, and the comparison of CD data with those of a synthesized model compound. Feeding studies suggest that the cyclopropanol moiety is generated by two one-carbon shortening events. Surprisingly, a knock-out strain impaired in polyketide production showed strong inhibition of other methylobacteria unlike the wild-type producer. The activity was inhibited by complementation with toblerols, suggesting that these compounds modulate an as-yet unknown methylobacterial antibiotic.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201709056

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