三七放线菌素的生物合成及其倍半萜环化酶的研究

A new natural product sanqimycin which exhibit antibacterial activity was isolated recently from endophytes Streptomyces sp. KIB015 by our group. Sanqimycin are hybrid natural products of both sesquiterpene and polyketide origin, and the sesquiterpene part of sanqimycin is a new skeleton unit. From the point of biosynthesis, the structural diversity of terpenoids are mainly from the function of terpene cyclase and oxidase, especially the terpene cyclase. And the novelty of terpene cyclase are reflected in two points, one is the novelty of compound structure, the other is the novelty of amino acid sequence or structure of enzyme. So the discovery of this new skeleton indicates that the terpene cyclase gene in the sanqimycin gene cluster is special and the biosynthetic pathway is new. we want to clone the gene cluster of sanqimycin. After that, we will characterize the functions of genes and proteins in sanqimycin biosynthetic pathway, especially the mechanism of the terpene cyclase.This study will hold the promise to find a new cyclization mechanism, and will facilitate and set the stage to biosynthetically engineer new sanqimycin analogues by combinatorial biosynthesis and synthetic biology.

三七放线菌素是本研究组最近从三七植物内生放线菌Streptomyces sp. KIB015中发现的具抗菌活性的新天然产物。三七放线菌素为倍半萜与聚酮的杂合体，其中三七放线菌素的倍半萜骨架为一新骨架单元。从生物合成的角度来看，萜类化合物的结构多样性主要来源于萜类环化酶和后修饰氧化酶，尤其是创造碳骨架单元多样性的萜类环化酶。而环化酶的新颖性主要体现在研究对象结构的新颖性和酶本身的氨基酸序列或立体结构的新颖性。这一新骨架倍半萜的发现预示着三七放线菌素生物合成基因簇中环化酶基因的独特性。本研究将得到三七放线菌素的生物合成基因簇，并在此基础上研究相关的各个基因及其编码蛋白的功能，进而在基因水平和酶学水平上阐明该类分子的组装机理，特别是三七放线菌素中新骨架倍半萜环化酶的催化机理。总之，开展三七放线菌素的生物合成研究有望发现酶催化的萜类环化的新化学机制，最终为组合生物合成与合成生物学研究打下基础。