Engineering substrate specificity of HAD phosphatases and multienzyme systems development for the thermodynamic-driven manufacturing sugars
Chaoyu Tian,
Jiangang Yang (),
Cui Liu,
Peng Chen,
Tong Zhang,
Yan Men,
Hongwu Ma (),
Yuanxia Sun () and
Yanhe Ma
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Chaoyu Tian: Chinese Academy of Sciences
Jiangang Yang: Chinese Academy of Sciences
Cui Liu: Chinese Academy of Sciences
Peng Chen: Chinese Academy of Sciences
Tong Zhang: Chinese Academy of Sciences
Yan Men: Chinese Academy of Sciences
Hongwu Ma: Chinese Academy of Sciences
Yuanxia Sun: Chinese Academy of Sciences
Yanhe Ma: Chinese Academy of Sciences
Nature Communications, 2022, vol. 13, issue 1, 1-13
Abstract:
Abstract Naturally, haloacid dehalogenase superfamily phosphatases have been evolved with broad substrate promiscuity; however, strong specificity to a particular substrate is required for developing thermodynamically driven routes for manufacturing sugars. How to alter the intrinsic substrate promiscuity of phosphatases and fit the “one enzyme-one substrate” model remains a challenge. Herein, we report the structure-guided engineering of a phosphatase, and successfully provide variants with tailor-made preference for three widespread phosphorylated sugars, namely, glucose 6-phosphate, fructose 6-phosphate, and mannose 6-phosphate, while simultaneously enhancement in catalytic efficiency. A 12000-fold switch from unfavorite substrate to dedicated one is generated. Molecular dynamics simulations reveal the origin of improved activity and substrate specificity. Furthermore, we develop four coordinated multienzyme systems and accomplish the conversion of inexpensive sucrose and starch to fructose and mannose in excellent yield of 94–96%. This innovative sugar-biosynthesis strategy overcomes the reaction equilibrium of isomerization and provides the promise of high-yield manufacturing of other monosaccharides and polyols.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31371-8
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DOI: 10.1038/s41467-022-31371-8
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