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Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production

[Image: see text] Allosteric proteins are considered as one of the most critical targets to design cell factories via synthetic biology approaches. Here, we proposed a molecular dynamics-based allosteric prediction method (MBAP) to screen indirect-binding sites and potential mutations for protein re...

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Autores principales: Wu, Mingyu, Sun, Yu, Zhu, Meiru, Zhu, Laiyu, Lü, Junhong, Geng, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153896/
https://www.ncbi.nlm.nih.gov/pubmed/34056250
http://dx.doi.org/10.1021/acsomega.1c00798
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author Wu, Mingyu
Sun, Yu
Zhu, Meiru
Zhu, Laiyu
Lü, Junhong
Geng, Feng
author_facet Wu, Mingyu
Sun, Yu
Zhu, Meiru
Zhu, Laiyu
Lü, Junhong
Geng, Feng
author_sort Wu, Mingyu
collection PubMed
description [Image: see text] Allosteric proteins are considered as one of the most critical targets to design cell factories via synthetic biology approaches. Here, we proposed a molecular dynamics-based allosteric prediction method (MBAP) to screen indirect-binding sites and potential mutations for protein re-engineering. Using this MBAP method, we have predicted new sites to relieve the allosteric regulation of threonine dehydrogenase (TD) by isoleucine. An obtained mutation P441L has been verified with the ability to significantly reduce the allosteric regulation of TD in vitro assays and with the fermentation application in vivo for amino-acid production. These findings have proved the MBAP method as an effective and efficient predicting tool to find new positions of the allosteric enzymes, thus opening a new path to constructing cell factories in synthetic biology.
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spelling pubmed-81538962021-05-27 Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production Wu, Mingyu Sun, Yu Zhu, Meiru Zhu, Laiyu Lü, Junhong Geng, Feng ACS Omega [Image: see text] Allosteric proteins are considered as one of the most critical targets to design cell factories via synthetic biology approaches. Here, we proposed a molecular dynamics-based allosteric prediction method (MBAP) to screen indirect-binding sites and potential mutations for protein re-engineering. Using this MBAP method, we have predicted new sites to relieve the allosteric regulation of threonine dehydrogenase (TD) by isoleucine. An obtained mutation P441L has been verified with the ability to significantly reduce the allosteric regulation of TD in vitro assays and with the fermentation application in vivo for amino-acid production. These findings have proved the MBAP method as an effective and efficient predicting tool to find new positions of the allosteric enzymes, thus opening a new path to constructing cell factories in synthetic biology. American Chemical Society 2021-04-15 /pmc/articles/PMC8153896/ /pubmed/34056250 http://dx.doi.org/10.1021/acsomega.1c00798 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Wu, Mingyu
Sun, Yu
Zhu, Meiru
Zhu, Laiyu
Lü, Junhong
Geng, Feng
Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production
title Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production
title_full Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production
title_fullStr Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production
title_full_unstemmed Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production
title_short Molecular Dynamics-Based Allosteric Prediction Method to Design Key Residues in Threonine Dehydrogenase for Amino-Acid Production
title_sort molecular dynamics-based allosteric prediction method to design key residues in threonine dehydrogenase for amino-acid production
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153896/
https://www.ncbi.nlm.nih.gov/pubmed/34056250
http://dx.doi.org/10.1021/acsomega.1c00798
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