CAS Key Laboratory of Microbial Physiological and Metabolic Engineering

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Director: Professor Yong Tao

Vice Director: Professor Shuangyan Tang

Areas of Research: The orientation of key laboratory is applied basic research in microbial biotechnology, focusing on industrial microbial physiology and regulation of metabolism, the reconstruction and optimization of biosynthesis pathway and physiological adaptation functionalities. Its three research directions are molecular genetics and efficient genetic manipulation systems, molecular enzyme engineering and new biocatalytic process, and molecular physiology and advanced metabolic engineering. Its objectives focus on the development of new technologies and new methods towards microbial physiological engineering and metabolic engineering, developing the next generation of strains and whole-cell catalysts with predominate industrial performance.

Research Teams: Our department has 11 research groups and 53 researchers including 1 CAS acdemician, 10 Professors, 11associate Professors, 26 assistant Professors, also has 4 post-doctor associates and 58 graduate students.

Research Progress:

1. Development of high efficient DNA module assembly and genetic manipulation technologies

In order to balances in gene expression of a metabolic pathway, we developed a new DNA assembling method, named oligo-linker mediated assembly (OLMA) method, to simultaneously vary promoter, RBS, gene order and species of enzymes. A unique feature of the method is the design of a chemically synthetic double-stranded DNA library to achieve the variations of promoter and RBS, and to facilitate the swapping of the gene order, resulting in a PCR-free and barcode-free DNA assembly approach. Through collaborative research and application of this technology, the PHA increased from 80% to 92% in the proportion of dry cell weight, and carotenoid production reached 80 mg/g DCW. The genetic manipulation system for Bacillus and yeast and the expression induced system in Escherichia coli were constructed; the recombinant efficiency in Bacillus subtilis increased 100 times.

2. Establishment of the platform for biocatalysis engineering based on HTP Screening

An efficient high-throughput screening method is developed for quantization of some small molecules, such as lactulose, azasugar, tetrahydropyrimidine, malonyl-CoA and etc. Using the directed evolution strategy and the high-throughput screening method, the synthesis efficiency of these small molecules in Escherichia coli is improved. The specific activity of alkaline pectinase and leucine dehydrogenase is increased significantly and the rare ginsenoside is efficiently synthesized by modifying glycosidase. The recombinant protein expression platform for Escherichia coli and Pichia pastoris is developed. The high-level expression of G protein, glucose oxidase,collagen and laccase were successfully achieved. For example, the expression level of glucose oxidase in Pichia pastoris has increased to nearly 10 times.

3. Development of novel biotechnological route for bio-chemicals production.

Using metabolic engineering and systems biology techniques, the direct fermentative production of L-histidine and serine is achieved for the first time. L-histidine production titer reached 14.15 g/L and L-Serine production titer reached 13.21 g/L. Research of L-lysine and L-threonine strain modification obtained CAS Award for Development of Science & Technology. As the important derivative of lysine, the production line of pentanediamine and nylon 5X is initially established. Through finding the new enzymes, analysis of rate-limiting enzyme, screening and expression regulation, several engineering strain are constructed, such as, to synthesize1,2,4-butanetriol and butenic acid. 1-Butanol yield is improved by 50% when reconstruction of the butanol synthesis pathway in Escherichia coli. The artificial biosynthetic pathway of (S)-(+)-1,2-propanediol from L-lactic acid is first developed. The whole-cell biocatalyst for G-7-ADCA production is significantly improved in engineered E. coli, which G-7-ADCA titer reached 10.3 g/L. Hyaluronic acid titer reached 11g/L. PSA titer reached 11.85 g/L. Highly efficient biosynthetic pathways of phenylethanol was assembled. An efficient whole-cell bioconversion process for β-alanine was established and commercialized. Through the prediction analysis and rational design, a super-strong promoter Pcpc560 is discovered and verified in cyanobacteria, which significantly improves the synthetic efficiency to chemicals production from CO2 using cyanobacteria as alternative hosts.