Overcoming the thermodynamic equilibrium of an isomerization reaction through oxidoreductive reactions for biotransformation

Jing-Jing Liu, Guo-Chang Zhang, Suryang Kwak, Eun Joong Oh, Eun Ju Yun, Kulika Chomvong, Jamie H. D. Cate and Yong-Su Jin ()
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Jing-Jing Liu: University of Illinois at Urbana-Champaign
Guo-Chang Zhang: University of Illinois at Urbana-Champaign
Suryang Kwak: University of Illinois at Urbana-Champaign
Eun Joong Oh: University of Illinois at Urbana-Champaign
Eun Ju Yun: University of Illinois at Urbana-Champaign
Kulika Chomvong: National Center for Genetic Engineering and Biotechnology (BIOTEC)
Jamie H. D. Cate: University of California
Yong-Su Jin: University of Illinois at Urbana-Champaign

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: Abstract Isomerases perform biotransformations without cofactors but often cause an undesirable mixture of substrate and product due to unfavorable thermodynamic equilibria. We demonstrate the feasibility of using an engineered yeast strain harboring oxidoreductase reactions to overcome the thermodynamic limit of an isomerization reaction. Specifically, a yeast strain capable of consuming lactose intracellularly is engineered to produce tagatose from lactose through three layers of manipulations. First, GAL1 coding for galactose kinase is deleted to eliminate galactose utilization. Second, heterologous xylose reductase (XR) and galactitol dehydrogenase (GDH) are introduced into the ∆gal1 strain. Third, the expression levels of XR and GDH are adjusted to maximize tagatose production. The resulting engineered yeast produces 37.69 g/L of tagatose from lactose with a tagatose and galactose ratio of 9:1 in the reaction broth. These results suggest that in vivo oxidoreaductase reactions can be employed to replace isomerases in vitro for biotransformation.

Date: 2019
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DOI: 10.1038/s41467-019-09288-6

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