BioChem - DOS

Optimal cofactor swapping can increase the theoretical yield for chemical production in Escherichia coli and Saccharomyces cerevisiae

Metabolic engineering

King, Z.A.; Feist, A.M.

Maintaining cofactor balance is a critical function in microorganisms, but often the native cofactor balance does not match the needs of an engineered metabolic flux state. Here, an optimization procedure is utilized to identify optimal cofactor-specificity ''swaps'' for oxidoreductase enzymes utilizing NAD(H) or NADP(H) in the genome-scale metabolic models of Escherichia coli and Saccharomyces cerevisiae. The theoretical yields of all native carbon-containing molecules are considered, as well as theoretical yields of twelve heterologous production pathways in E. coli. Swapping the cofactor specificity of central metabolic enzymes (especially GAPD and ALCD2x) is shown to increase NADPH production and increase theoretical yields for native products in E. coli and yeast-including l-aspartate, l-lysine, l-isoleucine, l-proline, l-serine, and putrescine-and non-native products in E. coli-including 1,3-propanediol, 3-hydroxybutyrate, 3-hydroxypropanoate, 3-hydroxyvalerate, and styrene.

2014

Academic Press

1096-7176

1096-7184

24

pp.117-128

10.1016/j.ymben.2014.05.009

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART69691723

Cofactor balancing; Escherichia coli; Saccharomyces cerevisiae; Constraint-based modeling; MILP; Theoretical yield; Metabolic engineering