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Design of Motifs Interfacial Interactions by Co-evolved Analysis of D-amino Acid Dehydrogenase for Stability Enhancement
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  • Zhehui Ji,
  • Qian Zhang,
  • Lingxuan Duan,
  • Lingling Dong,
  • Shizhen Wang
Zhehui Ji
Xiamen University
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Qian Zhang
Xiamen University
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Lingxuan Duan
Xiamen University
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Lingling Dong
Xiamen University
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Shizhen Wang
Xiamen University

Corresponding Author:[email protected]

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To design D-amino acid dehydrogenase (DAADH) for enhanced stability, the interactions of the subunit interfaces of DAADH were analyzed. Interaction network analysis of DAADH indicated that there are only weak interactions between the A and B subunits. Several co-evolved residue pairs were selected for mutation to enhance interfacial interactions of subunits, and 11 designed MDHs were obtained. DA06 and DA11 were selected for experimental verification for their salt bridges are 1.4 and 1.2-fold of that of DAwild, respectively. DA11 can maintain 93% activity in 80℃, while it was only 40% for DAwild. Thermostabiliy study indicated the half-life of DA11 was 2-fold of DAwild. Molecular dynamics simulations revealed that the extraordinary stability of the DA11 was due to the formation of extra interfacial salt bridges. The paper provided a strategy of mutations outside the active site of enzyme by co-evolutionary analysis which can reduce the effect of the activity-thermostability trade-off.
12 Feb 2023Submitted to AIChE Journal
07 Mar 2023Submission Checks Completed
07 Mar 2023Assigned to Editor
07 Mar 2023Review(s) Completed, Editorial Evaluation Pending
09 Mar 2023Reviewer(s) Assigned
20 Apr 2023Editorial Decision: Revise Major
05 May 20231st Revision Received
08 May 2023Assigned to Editor
08 May 2023Submission Checks Completed
08 May 2023Review(s) Completed, Editorial Evaluation Pending
11 May 2023Reviewer(s) Assigned
05 Jul 2023Editorial Decision: Revise Minor
07 Jul 20232nd Revision Received
08 Jul 2023Assigned to Editor
08 Jul 2023Submission Checks Completed
08 Jul 2023Review(s) Completed, Editorial Evaluation Pending
25 Jul 2023Editorial Decision: Accept