阿卡波糖及其结构类似杂质生物合成与调控的研究进展

Biosynthesis and regulatory mechanism of acarbose and its structural analogs:a review

阿卡波糖是一种用于Ⅱ型糖尿病治疗的糖苷酶抑制剂,工业上采用游动放线菌Actinoplanes sp.生产。作为一种次级代谢产物,阿卡波糖生物合成复杂,游动放线菌发酵液中除阿卡波糖外还会积累大量结构类似杂质组分。由于缺乏对阿卡波糖及其杂质合成和调控机制的系统了解,难以通过调控来阻断或降低杂质合成,从而导致纯化难度大。近年来,随着组学和分子生物学技术的发展,游动放线菌中阿卡波糖及其结构类似杂质的合成及调控机制的研究备受关注。研究人员通过生物信息学分析、基因工程技术以及酶学表征等手段探究了相关基因及其调控机制,文中对这方面的进展进行了综述。

Acarbose is widely used asα-glucosidase inhibitor in the treatment of typeⅡdiabetes.Actinoplanes sp.is used for industrial production of acarbose.As a secondary metabolite,the biosynthesis of acarbose is quite complex.In addition to acarbose,a few acarbose structural analogs are also accumulated in the culture broth of Actinoplanes sp.,which are hard to remove.Due to lack of systemic understanding of the biosynthesis and regulation mechanisms of acarbose and its structural analogs,it is difficult to eliminate or reduce the biosynthesis of the structural analogs.Recently,the advances in omics technologies and molecular biology have facilitated the investigations of biosynthesis and regulatory mechanisms of acarbose and its structural analogs in Actinoplanes sp..The genes involved in the biosynthesis of acarbose and its structural analogs and their regulatory mechanism have been extensively explored by using bioinformatics analysis,genetic manipulation and enzymatic characterization,which is summarized in this review.