Abstract：
:Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomoniasis, and mixed infections. Chemical instability has hindered its widespread 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 sequence 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 cluster, 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 pentamycin, suggesting pentamycin production may be common in Streptomyces species.
journal_name
ACS Chem Bioljournal_title
ACS chemical biologyauthors
Zhou S,Song L,Masschelein J,Sumang FAM,Papa IA,Zulaybar TO,Custodio AB,Zabala D,Alcantara EP,de Los Santos ELC,Challis GLdoi
10.1021/acschembio.9b00270subject
Has Abstractpub_date
2019-06-21 00:00:00pages
1305-1309issue
6eissn
1554-8929issn
1554-8937journal_volume
14pub_type
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