Suroto Dian Anggraini, Kitani Shigeru, Arai Masayoshi, Ikeda Haruo, Nihira Takuya
International Center for Biotechnology, Osaka University, Suita, Osaka, Japan.
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
PLoS One. 2018 Jan 11;13(1):e0190973. doi: 10.1371/journal.pone.0190973. eCollection 2018.
Phthoxazolin A, an oxazole-containing polyketide, has a broad spectrum of anti-oomycete activity and herbicidal activity. We recently identified phthoxazolin A as a cryptic metabolite of Streptomyces avermitilis that produces the important anthelmintic agent avermectin. Even though genome data of S. avermitilis is publicly available, no plausible biosynthetic gene cluster for phthoxazolin A is apparent in the sequence data. Here, we identified and characterized the phthoxazolin A (ptx) biosynthetic gene cluster through genome sequencing, comparative genomic analysis, and gene disruption. Sequence analysis uncovered that the putative ptx biosynthetic genes are laid on an extra genomic region that is not found in the public database, and 8 open reading frames in the extra genomic region could be assigned roles in the biosynthesis of the oxazole ring, triene polyketide and carbamoyl moieties. Disruption of the ptxA gene encoding a discrete acyltransferase resulted in a complete loss of phthoxazolin A production, confirming that the trans-AT type I PKS system is responsible for the phthoxazolin A biosynthesis. Based on the predicted functional domains in the ptx assembly line, we propose the biosynthetic pathway of phthoxazolin A.
恶唑啉A是一种含恶唑的聚酮化合物，具有广谱抗卵菌活性和除草活性。我们最近鉴定出恶唑啉A是阿维链霉菌的一种隐蔽代谢产物，该菌可产生重要的驱虫剂阿维菌素。尽管阿维链霉菌的基因组数据已公开，但在序列数据中并未发现明显的恶唑啉A生物合成基因簇。在此，我们通过基因组测序、比较基因组分析和基因破坏鉴定并表征了恶唑啉A（ptx）生物合成基因簇。序列分析发现，假定的ptx生物合成基因位于公共数据库中未发现的一个额外基因组区域，该额外基因组区域中的8个开放阅读框可在恶唑啉环、三烯聚酮和氨基甲酰基部分的生物合成中发挥作用。编码离散酰基转移酶的ptxA基因的破坏导致恶唑啉A产量完全丧失，证实反式-AT I型聚酮合酶系统负责恶唑啉A的生物合成。基于ptx装配线中预测的功能域，我们提出了恶唑啉A的生物合成途径。
