Sheng Yang

Personal Profile

Research Work

  Green chemistry is the design of chemical products and processes that reduce or eliminate the use or generation of hazardous substances (Anne E. Marteel et al., 2003). The US Environmental Protection Agency presented five projects each year as Presidential Green Chemistry Challenge Awards since 1996. Biocatalysis has won more than a quarter of 139 awards [https://www.epa.gov/greenchemistry]. However, the application of biocatalysis in the chemical industry is still quite limited partially because the development and implementation of biocatalysts is rather slow compared to chemical synthesis (Keasling et al., 2012).

  Key advances in DNA sequencing and gene synthesis provide tremendous resources and possibility for building biocatalysts by functional expression and reorganization of enzymes into new biosynthetic pathways (Bornscheuer et al., 2012). Our overall research goal is the development of synthetic biology-based biocatalysts for industrial use by providing new enabling technologies and novel designs. Our scientific objectives include 1) more efficient microbial genome editing tools for faster construction of designer cells, and 2) building genetically defined cells to understand the mechanism behind the efficient catalytic performance of evolved biocatalysts.

Main Achievements

    Our microbial genome editing plasmids have been distributed more than 4000 times to the global research community. Take advantage of our knowledge in microbial genetics, we participated in several human-health-related research projects involving gut bacteria -- Lactobacillus and Akkermansia muciniphila, and pathogens -- Acinetobacter baumannii and Clostridium difficule. We also engineered E. coli probiotics Nissle 1917 into live biotherapeutics to treat phenylketonuria and tumors.

    Using self-made genetic tools, we designed and obtained L-proline hyperproducing Corynebacterium glutamicum strains; converted Lactobacillus brevis as a 1-butanol producer; engineered clostridia (community) for conversion of biomass into 1-butanol; edited Yarrowia lipolytica to produce β-farnesene; displayed glucoamylase on the surface of industrial Saccharomyces cerevisiae cell to save the cost from starch to glucose. L-proline hyperproducer strain and glucoamylase-displayed yeast have been used commercially.

    We showcased the application of MUCICAT in gene dosage optimization for recombinant enzyme expression and generating combinatorial genomic diversity by simultaneously targeting up to 11 sites on the E. coli chromosome for multiplex gene interruption and/or insertion. MUCICATed E. coli strain with optimized cephalosporin C acylase gene copy has been used for industrial-scale preparation of this bulk enzyme because of its outstanding performance over the plasmid-based version.

    Lignocellulosic hydrolysates are generated by chemical pretreatment and hydrolysis of plant cell walls. The conversion of xylose into ethanol from hydrolysates containing microbial inhibitors is a major bottleneck in biofuel production. We identified sodium salts as the main yeast inhibitors and evolved a Saccharomyces cerevisiae strain overexpressing xylose catabolism genes in a xylose/glucose mixed medium containing sodium salts. The yeast has been used globally, producing more than twenty million gallons of cellulosic ethanol. We further elucidated that the amplification of xylA and XKS1-PPP and the mutations in NFS1, TRK1, SSK1, PUF2, and IRA1 were responsible and sufficient for lignocellulosic ethanol overproduction. Our evolved or reverse-engineered yeasts enabled industrial-scale lignocellulosic ethanol production (News: Novonesis and CAS Center for Excellence in Molecular Plant Sciences collaborate to expand pentose yeast for chemicals production beyond cellulosic ethanol) and facilitated phenotype transfer to yeast cell factories producing chemicals beyond ethanol.

Publications

https://www.researchgate.net/profile/Sheng_Yang10