RIKEN Center for Sustainable Resource Science, Chemical Biology Research Group, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
RIKEN Center for Sustainable Resource Science, Natural Product Biosynthesis Research Unit, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
J Nat Prod. 2020 Dec 24;83(12):3598-3605. doi: 10.1021/acs.jnatprod.0c00755. Epub 2020 Nov 20.
Verticilactam and the new geometric isomers, verticilactams B and C, were produced by heterologous expression of the biosynthetic gene cluster for verticilactam using the SUKA17 strain. Only verticilactam, a compound with a characteristic β-ketoamide unit within a 16-membered polyketide macrolactam conjugated with an octalin skeleton, had been previously reported having been isolated from JC-8444. In this report, minor verticilactam derivatives were isolated from the transformed strain, and their structures elucidated by spectral analysis. Verticilactam B was a geometric isomer at Δ and Δ, and verticilactam C was the Δ and Δ isomer. In addition, the absolute configuration of verticilactam was confirmed by ECD analysis and NMR chemical shifts. The stereochemistry assignments of the hydroxy groups at C-10 and C-12 were supported by the domain organization of the polyketide synthase identified in the verticilactam gene cluster. Verticilactam showed moderate activity against the malaria parasite 3D7 strain with no significant cytotoxicity or antimicrobial effects.
利用 SUKA17 菌株通过异源表达 verticilactam 的生物合成基因簇，产生了 verticilactam 和新的立体异构体 verticilactam B 和 C。先前从 JC-8444 中分离得到的 verticilactam 是一种具有特征性β-酮酰胺单元的化合物，该单元在与辛烷骨架共轭的 16 元聚酮大环内酯中。在本报告中，从转化菌株中分离出了少量的 verticilactam 衍生物，并通过光谱分析阐明了它们的结构。Verticilactam B 是 Δ 和 Δ 的立体异构体，而 verticilactam C 是 Δ 和 Δ 的异构体。此外，通过 ECD 分析和 NMR 化学位移确定了 verticilactam 的绝对构型。通过鉴定的 verticilactam 基因簇中的聚酮合酶的结构域组织，支持了 C-10 和 C-12 位羟基的立体化学构象。Verticilactam 对疟原虫 3D7 株具有中等的活性，没有明显的细胞毒性或抗菌作用。
