链霉菌中高效生产聚酮化合物的研究方法及进展

Efficient production of polyketide products in Streptomyces hosts-A review

摘要:

聚酮化合物是通过聚酮合成途径产生的一大类结构和生物活性多样的次级代谢产物,是链霉菌产生的主要次级代谢产物,具有重要的经济价值。为了在链霉菌中提高聚酮化合物产量,以满足工业生产需求,近年来,代谢工程的方法被广泛应用,例如,过表达合成途径中限速酶或途径特异性激活蛋白、强化前体供应、去除产物反馈抑制、合成基因簇异源表达等。本文将从代谢工程改造实例入手,全面综述链霉菌中聚酮化合物高效生物合成的研究方法及进展,并对利用合成生物学策略智能动态适配各个相关途径,进而提高该类化合物产量的研究思路进行展望。

Abstract:

Polyketides represent an important class of structurally and functionally diverse secondary metabolites with high economic value. Among bacteria, Streptomycetes are the main producers of polyketides. To enhance polyketide production in Streptomyces hosts, rational metabolic engineering approaches have been applied, such as overexpressing rate-limiting enzymes, or transcriptional activator, increasing the supply of precursor, removing feedback inhibition by end products and heterologous expression of polyketide biosynthetic gene clusters. In this review, we discuss examples of successful metabolic engineering strategies used to improve polyketide production in Streptomycetes. Meanwhile, we also address future prospective, emerging synthetic biology strategies to dynamically adjust the metabolic fluxes of pathways related to polyketide synthesis.