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Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide

The β‐nicotinamide mononucleotide (NMN) is a key intermediate of an essential coenzyme for cellular redox reactions, NAD. Administration of NMN is reported to improve various symptoms, such as diabetes and age‐related physiological decline. Thus, NMN is attracting much attention as a promising nutra...

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Detalles Bibliográficos
Autores principales: Liu, Yang, Yasawong, Montri, Yu, Bo
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/PMC8601175/
https://www.ncbi.nlm.nih.gov/pubmed/34310854
http://dx.doi.org/10.1111/1751-7915.13901
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author Liu, Yang
Yasawong, Montri
Yu, Bo
author_facet Liu, Yang
Yasawong, Montri
Yu, Bo
author_sort Liu, Yang
collection PubMed
description The β‐nicotinamide mononucleotide (NMN) is a key intermediate of an essential coenzyme for cellular redox reactions, NAD. Administration of NMN is reported to improve various symptoms, such as diabetes and age‐related physiological decline. Thus, NMN is attracting much attention as a promising nutraceutical. Here, we engineered an Escherichia coli strain to produce NMN from cheap substrate nicotinamide (NAM) and glucose. The supply of in vivo precursor phosphoribosyl pyrophosphate (PRPP) and ATP was enhanced by strengthening the metabolic flux from glucose. A nicotinamide phosphoribosyltransferase with high activity was newly screened, which is the key enzyme for converting NAM to NMN with PRPP as cofactor. Notably, the E. coli endogenous protein YgcS, which function is primarily in the uptake of sugars, was firstly proven to be beneficial for NMN production in this study. Fine‐tuning regulation of ygcS gene expression in the engineered E. coli strain increased NMN production. Combined with process optimization of whole‐cell biocatalysts reaction, a final NMN titre of 496.2 mg l(‐1) was obtained.
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spelling pubmed-86011752021-11-24 Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide Liu, Yang Yasawong, Montri Yu, Bo Microb Biotechnol Research Articles The β‐nicotinamide mononucleotide (NMN) is a key intermediate of an essential coenzyme for cellular redox reactions, NAD. Administration of NMN is reported to improve various symptoms, such as diabetes and age‐related physiological decline. Thus, NMN is attracting much attention as a promising nutraceutical. Here, we engineered an Escherichia coli strain to produce NMN from cheap substrate nicotinamide (NAM) and glucose. The supply of in vivo precursor phosphoribosyl pyrophosphate (PRPP) and ATP was enhanced by strengthening the metabolic flux from glucose. A nicotinamide phosphoribosyltransferase with high activity was newly screened, which is the key enzyme for converting NAM to NMN with PRPP as cofactor. Notably, the E. coli endogenous protein YgcS, which function is primarily in the uptake of sugars, was firstly proven to be beneficial for NMN production in this study. Fine‐tuning regulation of ygcS gene expression in the engineered E. coli strain increased NMN production. Combined with process optimization of whole‐cell biocatalysts reaction, a final NMN titre of 496.2 mg l(‐1) was obtained. John Wiley and Sons Inc. 2021-07-26 /pmc/articles/PMC8601175/ /pubmed/34310854 http://dx.doi.org/10.1111/1751-7915.13901 Text en © 2021 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd. 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
Liu, Yang
Yasawong, Montri
Yu, Bo
Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide
title Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide
title_full Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide
title_fullStr Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide
title_full_unstemmed Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide
title_short Metabolic engineering of Escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide
title_sort metabolic engineering of escherichia coli for biosynthesis of β‐nicotinamide mononucleotide from nicotinamide
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601175/
https://www.ncbi.nlm.nih.gov/pubmed/34310854
http://dx.doi.org/10.1111/1751-7915.13901
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