酿酒酵母合成木栓酮及其衍生物的研究现状及展望

Research status and prospect of the synthesis of friedelin and its derivatives by Saccharomyces cerevisiae

摘要:

木栓酮及其衍生物在植物中普遍存在且种类繁多，具有丰富的生理药理学活性。木栓酮衍生物是以木栓酮为骨架经细胞色素氧化酶P450 (cytochrome P450, CYP450)及UDP葡萄糖醛酸转移酶(UDP-glucuronosyltransferase, UGT)修饰而来。植物中天然木栓酮及其衍生物的含量极低，传统的萃取分离和化学合成效率低、能耗高且污染环境，因此，利用酿酒酵母作为宿主菌生产木栓酮及其衍生物是一种高效且环保的策略。本文从增加前体含量、提高酶活性和产物合成的亚细胞定位等方面介绍并展望了木栓酮在酿酒酵母中高效生产的策略，并介绍了目前几种常见的木栓酮衍生物研究现状，从根据碳骨架相似性挖掘CYP450、蛋白质工程改造CYP450和合成代谢基因簇的挖掘等方面展望了木栓酮衍生物的合成途径解析的新思路。

Abstract:

Friedelin and its derivatives are ubiquitous in plants, with a wide variety of physiological and pharmacological activities. The derivatives of friedelin are modified from friedelin by cytochrome P450 oxidase (CYP450) and UDP-glucuronosyltransferase (UGT). Because of the extremely low content of natural friedelin and its derivatives in plants, the traditional extraction and chemical synthesis methods are inefficient, energy-consuming, and pollute the environment. Therefore, using Saccharomyces cerevisiae as the host bacteria to produce friedelin and its derivatives is an efficient and environmentally friendly approach. In this paper, we introduced and looked forward to the efficient production of friedelin in S. cerevisiae from the aspects of increasing precursor content, improving enzyme activity, and subcellular localization of product synthesis. In addition, this paper reviewed the current research status of several common friedelin derivatives, and put forward new ways for the synthesis of friedelin derivatives from the aspects of mining CYP450 based on carbon skeleton similarity, modifying CYP450 by protein engineering, and mining the gene clusters involved in the synthesis.