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A review article on microbial synthesis of natural products published by the Dalian Chemical Institute
[ Instrument Network Instrument R & D ] Recently, the team of Zhou Yongjin, a researcher of the Biocatalysis Innovation Special Zone Research Group of the Dalian Institute of Chemical Physics, Chinese Academy of Sciences, published a review article entitled Advanced Strategies for Production of Natural Products in Yeast. This article discusses the recent advances in synthetic biology and metabolic engineering strategies to construct yeast cell catalysts to achieve heterogeneous synthesis of complex natural products, and looks forward to the opportunities and challenges that exist.
50% of small molecule drugs used clinically are derived directly or indirectly from natural products. However, when an active natural product is expected to become a clinical drug or lead compound, its limited biological resources often become a rate-limiting step for large-scale applications. The rapid development of synthetic biology and metabolic engineering provides new ideas for the rapid acquisition of scarce natural products. Due to its good growth performance, yeast is widely used in the synthesis of natural product molecules and biochemicals.
This review proposes a "three-dimensional" metabolic engineering strategy for yeast cell catalyst construction, namely point, line, and area engineering perspectives. Points, lines, and surfaces refer to optimization of engineering modules, dynamic optimization of metabolic pathways, and global optimization of cell robustness, respectively. The article specifically points out the importance of cofactors as targets for metabolic regulation. In addition to participating in the respiratory chain and redox balance, the level and state of cofactors determine the efficiency of biological enzymes or biosynthetic pathways. The article concludes that building non-traditional yeast cell catalysts, developing novel synthetic biology technologies, and combining artificial intelligence will further enhance the efficiency of natural product biosynthesis.
Zhou Yongjin's team is committed to the construction and optimization of microorganisms, especially yeast cell catalysts. He has constructed Saccharomyces cerevisiae catalysts and efficiently synthesized fatty acid derivatives (Cell, 2018; ACS Syn. Bio., 2018). Recently, the research team carried out research on methanol biotransformation in conjunction with the clean energy layout of the Dalian Institute of Chemical Research. They constructed and optimized a methanol yeast catalyst to efficiently convert methanol into biofuels, biochemicals, and natural products (Nat. Energy, 2018; FEMS Yeast Res., 2019).
The review was published on iScience. Postdoctoral fellow Chen Ruibing and PhD student Yang Shan of Dalian Institute of Chemical Industry were co-first authors. This work was supported by the National Key Research and Development Program, the National Natural Science Foundation of China, the Xingliao Talent Program, and the Joint Research and Innovation Fund of the Dalian Institute of Chemical Technology and Qingdao Energy Institute.