Verticilactam and the new geometric isomers, verticilactams B and C, were produced by heterologous expression of the biosynthetic gene cluster for verticilactam using the Streptomyces avermitilis 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 Streptomyces spiroverticillatus 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 Δ¹⁷ and Δ¹⁹, and verticilactam C was the Δ¹⁹ and Δ²¹ 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 Plasmodium falciparum 3D7 strain with no significant cytotoxicity or antimicrobial effects.

中文翻译：

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轮内酰胺生物合成基因簇的异源表达及类似物鉴定

轮内酰胺和新的几何异构体、轮内酰胺 B 和 C 是通过使用阿维链霉菌SUKA17 菌株对轮内酰胺生物合成基因簇进行异源表达而产生的。只有轮转内酰胺是一种化合物，它在 16 元聚酮大环内酰胺中具有特征性的 β-酮酰胺单元，该化合物与奥克林骨架结合，之前曾报道从Streptomyces spiroverticillatus JC-8444 中分离出来。在本报告中，从转化菌株中分离出少量的枝条内酰胺衍生物，并通过光谱分析阐明了它们的结构。轮内酰胺 B 是 Δ ¹⁷和 Δ ¹⁹处的几何异构体，而轮内酰胺 C 是 Δ ¹⁹和 Δ ²¹处的几何异构体异构体。此外，通过 ECD 分析和 NMR 化学位移证实了枝条内酰胺的绝对构型。C-10 和 C-12 羟基的立体化学分配得到了在轮内酰胺基因簇中鉴定的聚酮化合物合酶的结构域组织的支持。Verticilactam 对疟原虫恶性疟原虫3D7 菌株表现出中等活性，没有显着的细胞毒性或抗菌作用。