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Pentamycin biosynthesis in Philippine Streptomyces sp. S816: Cytochrome P450-catalysed installation of the C-14 hydroxyl group.

08:00 EDT 16th May 2019 | BioPortfolio

Summary of "Pentamycin biosynthesis in Philippine Streptomyces sp. S816: Cytochrome P450-catalysed installation of the C-14 hydroxyl group."

Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomoniasis and mixed infections. Chemical instability has hindered its wide-spread application and development as a drug. Here we report the identification of Streptomyces sp. S816, isolated from Philippine mangrove soil, as a pentamycin producer. Genome se-quence analysis identified the putative pentamycin biosynthetic gene cluster, which shows a high degree of similarity to the gene cluster responsible for filipin III biosynthesis. The ptnJ gene, which is absent from the filipin III biosynthetic gene clus-ter, was shown to encode a cytochrome P450 capable of converting filipin III to pentamycin. This confirms that the cluster directs pentamycin biosynthesis, paving the way for biosynthetic engineering approaches to the production of pentamycin analogues. Several other Streptomyces genomes were found to contain ptnJ orthologues clustered with genes encoding polyketide synthases that appear to have similar architectures to those responsible for the assembly of filipin III and pen-tamycin, suggesting pentamycin production may be common in Streptomyces species.

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This article was published in the following journal.

Name: ACS chemical biology
ISSN: 1554-8937
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