Scientists have revealed a new mechanism for biosynthetics of akabo sugar

The Bai Linquan team, a professor at shanghai Jiaoda University's School of Life Sciences and the National Key Laboratory of Microbial Metabolism, analyzed the biosynthetic mechanism of the anti-diabetic drug Acapo sugar in depth and further improved the production of Acabo sugar through effective metabolic engineering strategies. The results of the study were published recently in Nature - Newsletter.
Shanghai Jiaotong University Ph.D. student Zhao Canqin is the first author of the paper, Bai Linquan is the author of the communication, the author also includes
academician Deng Zixin and Tarimu University professor
akabo sugar is α-glycosidease inhibitor natural products, clinically as a first-line drug is widely used in the treatment of type 2 diabetes, the demand is high, the annual market sales of more than 7 billion yuan. In industry, Acapo sugar is mainly produced by fermentation of swimming line bacteria. Due to the complex biosynthetic path and the production of a variety of by-products and structural similars, the yield is low and the post-extraction process is very cumbersome. Therefore, it is the key problem that needs to be solved urgently to construct efficient production strains and improve the level of industrial production. However, since most biosynthetic pathways are not yet known, this has seriously hampered the significant increase in yield through metabolic engineering modifications.
, the researchers identified two large accumulations of sub-abortions from the Acapo sugar synthesis pathway in fermentation fluids. Through the in-depth study of these sub-abortions and the system of their formation, the functions of cyclool dehydrase AbL and NADPH-dependent redoxase AbN are clarified, and the biosynthetic pathway of acaposal sugar is modified. At the same time, through comparative transcription group analysis, it is found that the inefficient biosynthetic part of amino deoxygenate is one of the main causes of the formation of sub-abortion. At the same time, the researchers, guided by the "open source intercepting" strategy, used a variety of metabolic engineering and synthetic biology methods, on the one hand, through multi-gene knockout to minimize the accumulation of sub-abortions, on the other hand, through the introduction of heterogenetically efficient amino deoxygenation synthesis genes to improve their synthesis ability, promote the effective use of C7-cyclol intermediates, and ultimately increase the production of Acapo sugar by 1.2 times to 7.4 grams per liter.
The study broke the silence of nearly 20 years of research on the biosynthesis mechanism of akabo sugar, and was the first systematic and effective modification of its bacteria by molecular biology and synthetic biology, which laid a solid foundation for the targeted high yield of akabo sugar and the improvement of international competitiveness in this field.
experts say the study not only highlights the importance of sub-abortions in the synthesis and yield of microbial drugs, but also reveals a variety of cross-dialogue between primary and secondary metabolism that can more effectively guide the high-yield modification of microbial drugs. The study demonstrated the long-term research accumulation of Deng Zixin's team on amino cyclool natural products such as jingoxin and acapolypse, and the efficient genetic operating system, wellgangmycin metabolic intermediates and key enzymes, amino cyclol synthesis mechanism hypothesis, etc. are the key to the breakthrough in this study.
the study was supported by key projects and joint fund projects of the National Natural Science Foundation of China, key research and development projects of the State, and basic research projects of the Shanghai Science and Technology Commission. (Source: Huang Xin, China Science Journal)
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