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Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway

Nicotinamide adenine dinucleotide (NAD(+)) is a life essential molecule involved in versatile biological processes. To date, only two de novo biosynthetic routes to NAD(+) are described, both of which start from a proteinogenic amino acid and are tightly controlled. Here, a de novo quinolinic acid p...

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Autores principales: Ding, Yong, Li, Xinli, Horsman, Geoff P., Li, Pengwei, Wang, Min, Li, Jine, Zhang, Zhilong, Liu, Weifeng, Wu, Bian, Tao, Yong, Chen, Yihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097395/
https://www.ncbi.nlm.nih.gov/pubmed/33977072
http://dx.doi.org/10.1002/advs.202004632
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author Ding, Yong
Li, Xinli
Horsman, Geoff P.
Li, Pengwei
Wang, Min
Li, Jine
Zhang, Zhilong
Liu, Weifeng
Wu, Bian
Tao, Yong
Chen, Yihua
author_facet Ding, Yong
Li, Xinli
Horsman, Geoff P.
Li, Pengwei
Wang, Min
Li, Jine
Zhang, Zhilong
Liu, Weifeng
Wu, Bian
Tao, Yong
Chen, Yihua
author_sort Ding, Yong
collection PubMed
description Nicotinamide adenine dinucleotide (NAD(+)) is a life essential molecule involved in versatile biological processes. To date, only two de novo biosynthetic routes to NAD(+) are described, both of which start from a proteinogenic amino acid and are tightly controlled. Here, a de novo quinolinic acid pathway starting from chorismate, which provides an alternative route (named as the C3N pathway) to NAD(+) biosynthesis, is established. Significantly, the C3N pathway yields extremely high cellular concentrations of NAD(H) in E. coli. Its utility in cofactor engineering is demonstrated by introducing the four‐gene C3N module to cell factories to achieve higher production of 2,5‐dimethylpyrazine and develop an efficient C3N‐based whole‐cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms.
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spelling pubmed-80973952021-05-10 Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway Ding, Yong Li, Xinli Horsman, Geoff P. Li, Pengwei Wang, Min Li, Jine Zhang, Zhilong Liu, Weifeng Wu, Bian Tao, Yong Chen, Yihua Adv Sci (Weinh) Research Articles Nicotinamide adenine dinucleotide (NAD(+)) is a life essential molecule involved in versatile biological processes. To date, only two de novo biosynthetic routes to NAD(+) are described, both of which start from a proteinogenic amino acid and are tightly controlled. Here, a de novo quinolinic acid pathway starting from chorismate, which provides an alternative route (named as the C3N pathway) to NAD(+) biosynthesis, is established. Significantly, the C3N pathway yields extremely high cellular concentrations of NAD(H) in E. coli. Its utility in cofactor engineering is demonstrated by introducing the four‐gene C3N module to cell factories to achieve higher production of 2,5‐dimethylpyrazine and develop an efficient C3N‐based whole‐cell bioconversion system for preparing chiral amines. The wide distribution and abundance of chorismate in most kingdoms of life implies a general utility of the C3N pathway for modulating cellular levels of NAD(H) in versatile organisms. John Wiley and Sons Inc. 2021-03-01 /pmc/articles/PMC8097395/ /pubmed/33977072 http://dx.doi.org/10.1002/advs.202004632 Text en © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Ding, Yong
Li, Xinli
Horsman, Geoff P.
Li, Pengwei
Wang, Min
Li, Jine
Zhang, Zhilong
Liu, Weifeng
Wu, Bian
Tao, Yong
Chen, Yihua
Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway
title Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway
title_full Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway
title_fullStr Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway
title_full_unstemmed Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway
title_short Construction of an Alternative NAD(+) De Novo Biosynthesis Pathway
title_sort construction of an alternative nad(+) de novo biosynthesis pathway
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097395/
https://www.ncbi.nlm.nih.gov/pubmed/33977072
http://dx.doi.org/10.1002/advs.202004632
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