Engineering a BsBDHA substrate-binding pocket entrance for the improvement in catalytic performance toward (R)-phenyl-1,2-ethanediol based on the computer-aided design

Hu, Bo-Chun; Li, Mengran; Li, Yingying; Yuan, Xin-Shuang; Hu, Yu-Ye; Xiao, Fugang

doi:10.1016/j.bej.2023.108907

Biochemical Engineering Journal

2023

DOI: 10.1016/j.bej.2023.108907

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Engineering a BsBDHA substrate-binding pocket entrance for the improvement in catalytic performance toward (R)-phenyl-1,2-ethanediol based on the computer-aided design

Bo-Chun Hu

Mengran Li

Yingying Li

et al.

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2024

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Cited by 4 publications

References 33 publications

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Rational design of short‐chain dehydrogenase/reductase for enantio‐complementary synthesis of chiral 1,2‐diols by successive hydroxymethylation and reduction of aldehydes

Ren,

Su,

et al. 2024

Biotech & Bioengineering

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Enantiopure 1,2‐diols are widely used in the production of pharmaceuticals, cosmetics, and functional materials as essential building blocks or bioactive compounds. Nevertheless, developing a mild, efficient and environmentally friendly biocatalytic route for manufacturing enantiopure 1,2‐diols from simple substrate remains a challenge. Here, we designed and realized a step‐wise biocatalytic cascade to access chiral 1,2‐diols starting from aromatic aldehyde and formaldehyde enabled by a newly mined benzaldehyde lyase from Sphingobium sp. combined with a pair of tailored‐made short‐chain dehydrogenase/reductase from Pseudomonas monteilii (PmSDR‐MuR and PmSDR‐MuS) capable of producing (R)‐ and (S)‐1‐phenylethane‐1,2‐diol with 99% ee. The planned biocatalytic cascade could synthesize a series of enantiopure 1,2‐diols with a broad scope (16 samples), excellent conversions (94%–99%), and outstanding enantioselectivity (up to 99% ee), making it an effective technique for producing chiral 1,2‐diols in a more environmentally friendly and sustainable manner.

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Rational design of short‐chain dehydrogenase/reductase for enantio‐complementary synthesis of chiral 1,2‐diols by successive hydroxymethylation and reduction of aldehydes

Ren,

Su,

et al. 2024

Biotech & Bioengineering

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The critical role of residues Phe120 and Val161 of (2 R,3 R)‑2,3‑butanediol dehydrogenase from Neisseria gonorrhoeae as probed by molecular docking and site‐directed mutagenesis

Dong,

Zhang,

Gui

et al. 2024

J Basic Microbiol

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NAD+‐dependent (2 R,3 R)‑2,3‑butanediol dehydrogenase (BDH) from Neisseria gonorrhoeae (NgBDH) is a representative member of the medium‐chain dehydrogenase/reductase (MDR) superfamily. To date, little information is available on the substrate binding sites and catalytic residues of BDHs from this superfamily. In this work, according to molecular docking studies, we found that conserved residues Phe120 and Val161 form strong hydrophobic interactions with both (2 R,3 R)‑2,3‑butanediol (RR‐BD) and meso‐2,3‑butanediol (meso‐BD) and that mutations of these residues to alanine or threonine impair substrate binding. To further evaluate the roles of these two residues, Phe120 and Val161 were mutated to alanine or threonine. Kinetic analysis revealed that, relative to those of wild type, the apparent KM values of the Phe120Ala mutant for RR‐BD and meso‐BD increased 36‐ and 369‐fold, respectively; the catalytic efficiencies of this mutant with RR‐BD and meso‐BD decreased approximately 586‐ and 3528‐fold, respectively; and the apparent KM values of the Val161Ala mutant for RR‐BD and meso‐BD increased 4‐ and 37‐fold, respectively, the catalytic efficiencies of this mutant with RR‐BD and meso‐BD decreased approximately 3‐ and 28‐fold, respectively. Additionally, the Val161Thr mutant slightly decreased catalytic efficiencies (twofold with RR‐BD; 7.3‐fold with meso‐BD) due to an increase in KM (sixfold for RR‐BD; 24‐fold for meso‐BD) and a slight increase (2.8‐fold with RR‐BD; 3.3‐fold with meso‐BD) in kcat. These findings validate the critical roles of Phe120 and Val161 of NgBDH in substrate binding and catalysis. Overall, the current study provides a better understanding of the substrate binding and catalysis of BDHs within the MDR superfamily.

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Significantly enhanced specific activity of Bacillus subtilis (2,3)-butanediol dehydrogenase through computer-aided refinement of its substrate-binding pocket

Hu,

Xi,

Xiao

et al. 2024

International Journal of Biological Macromolecules

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Engineering a BsBDHA substrate-binding pocket entrance for the improvement in catalytic performance toward (R)-phenyl-1,2-ethanediol based on the computer-aided design

Cited by 4 publications

References 33 publications

Rational design of short‐chain dehydrogenase/reductase for enantio‐complementary synthesis of chiral 1,2‐diols by successive hydroxymethylation and reduction of aldehydes

Rational design of short‐chain dehydrogenase/reductase for enantio‐complementary synthesis of chiral 1,2‐diols by successive hydroxymethylation and reduction of aldehydes

The critical role of residues Phe120 and Val161 of (2 R,3 R)‑2,3‑butanediol dehydrogenase from Neisseria gonorrhoeae as probed by molecular docking and site‐directed mutagenesis

Significantly enhanced specific activity of Bacillus subtilis (2,3)-butanediol dehydrogenase through computer-aided refinement of its substrate-binding pocket

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