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SJTU Research Team Made Beakthrough in Acarbose Biosynthesis

April 02, 2020      Author: Zhao Qinqin, Bai Linquan

Recently, a paper entitled "A severe leakage of intermediates to shunt products in acarbose biosynthesis" was published in Nature Communications by Bai Linquan's Team from State Key Laboratory of Microial Metabolism, SJTU School of Life Sciences and Biotechnology. The first author of this thesis is doctoral student Zhao Qinqin, and the corresponding author is Professor Bai Linquan. Academician Deng Zixin and Professor Zhang Lili from Tarim University are co-authors.

The research is sponsored by key projects and joint fund projects of the National Natural Science Foundation of China, National Key R&D Program of China and Basic Research Project of Shanghai Science and Technology Commission.

Abstract

The α-glucosidase inhibitor acarbose, produced by Actinoplanes sp. SE50/110, is a well-known drug for the treatment of type 2 diabetes mellitus. However, the largely unexplored biosynthetic mechanism of this compound has impeded further titer improvement. Herein, we uncover that 1-epi-valienol and valienol, accumulated in the fermentation broth at a strikingly high molar ratio to acarbose, are shunt products that are not directly involved in acarbose biosynthesis. Additionally, we find that inefficient biosynthesis of the amino-deoxyhexose moiety plays a role in the formation of these shunt products. Therefore, strategies to minimize the flux to the shunt products and to maximize the supply of the amino-deoxyhexose moiety are implemented, which increase the acarbose titer by 1.2-fold to 7.4 g L-1. This work provides insights into the biosynthesis of the C7-cyclitol moiety and highlights the importance of assessing shunt product accumulation when seeking to improve the titer of microbial pharmaceutical products.

 

Link: https://www.nature.com/articles/s41467-020-15234-8


Translated by Fu Jing    Reviewed by Wang Bingyu