Discovery of a Novel Spiro-Naphthoquinone Compound in Streptomyces aureus SP-371

Abstract

By overexpressing the positive regulatory gene, the silent gene cluster tjh in Streptomyces aureus SP-371 was successfully activated. The mutant strain could produce compounds with two distinct core strucutures which are pentacyclic and tetracyclic structures. It was speculated that these two types of skeletons might be derived from the same intermediate through two different post-modified pathways. These two tailoring pathways were intercepted by the double gene knockout, and aureuspiro was successfully accumulated in the mutant. Aureuspiro is a new natural product with a novel spiro-naphthoquinone structure. Despite aureuspiro is not a true intermediate in the biosynthesis of final products, it could support the hypothesis about structure of the common intermediate. Keywords genome mining; biosynthesis; type II polyketides natural product; spiro ring 1 结果与讨论 1.1 ∆tjhC5/∆tjhD5 双敲除突变株的构建 在单基因敲除实验中, 不仅证明了最终的两类化合 物是从共同中间体经由两种不同的后修饰途径得到的, 还成功确定了与各自后修饰途径相关的基因. 我们发现 tjhC5, tjhD2, tjhD4 和 tjhO5 只参与了线性四环结构化合 物的后修饰, tjhO4, tjhD3, tjhD5 和 tjhD1 的敲除只对五 元稠环结构化合物的产生有影响(Scheme 1