Department of Chemistry , University of Warwick , Coventry CV4 7AL , United Kingdom.
National Institute of Molecular Biology and Biotechnology (BIOTECH) , University of the Philippines Los Baños , Los Baños , Laguna 4031 , Philippines.
ACS Chem Biol. 2019 Jun 21;14(6):1305-1309. doi: 10.1021/acschembio.9b00270. Epub 2019 May 31.
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.
戊烷脒是一种多烯类抗生素，在瑞士注册用于治疗阴道念珠菌病、滴虫病和混合感染。化学不稳定性阻碍了其作为药物的广泛应用和发展。在这里，我们报告了从菲律宾红树林土壤中分离出的链霉菌 S816 是戊烷脒的生产者。基因组序列分析鉴定了戊烷脒生物合成基因簇，该基因簇与负责 filipin III 生物合成的基因簇具有高度相似性。ptnJ 基因缺失了 filipin III 生物合成基因簇，该基因编码一种细胞色素 P450，能够将 filipin III 转化为戊烷脒。这证实了该基因簇指导戊烷脒的生物合成，为戊烷脒类似物的生物合成工程方法铺平了道路。还发现其他几种链霉菌基因组中含有与聚酮合酶基因簇聚在一起的 ptnJ 同源物，这些基因簇似乎具有与负责组装 filipin III 和戊烷脒的基因类似的结构，这表明戊烷脒的产生可能在链霉菌属中很常见。
