High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase

Abstract Background Agmatine is a member of biogenic amines and is an important medicine which is widely used to regulate body balance and neuroprotective effects. At present, the industrial production of agmatine mainly depends on the chemical method, but it is often accompanied by problems includi...

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Main Authors: Fengyu Yang, Jiayu Xu, Yichun Zhu, Yi Wang, Meijuan Xu, Zhiming Rao
Format: Article
Language:English
Published: BMC 2022-01-01
Series:Microbial Cell Factories
Subjects:
Online Access:https://doi.org/10.1186/s12934-022-01742-3
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author Fengyu Yang
Jiayu Xu
Yichun Zhu
Yi Wang
Meijuan Xu
Zhiming Rao
author_facet Fengyu Yang
Jiayu Xu
Yichun Zhu
Yi Wang
Meijuan Xu
Zhiming Rao
author_sort Fengyu Yang
collection DOAJ
description Abstract Background Agmatine is a member of biogenic amines and is an important medicine which is widely used to regulate body balance and neuroprotective effects. At present, the industrial production of agmatine mainly depends on the chemical method, but it is often accompanied by problems including cumbersome processes, harsh reaction conditions, toxic substances production and heavy environmental pollution. Therefore, to tackle the above issues, arginine decarboxylase was overexpressed heterologously and rationally designed in Corynebacterium crenatum to produce agmatine from glucose by one-step fermentation. Results In this study, we report the development in the Generally Regarded as Safe (GRAS) l-arginine-overproducing C. crenatum for high-titer agmatine biosynthesis through overexpressing arginine decarboxylase based on metabolic engineering. Then, arginine decarboxylase was mutated to release feedback inhibition and improve catalytic activity. Subsequently, the specific enzyme activity and half-inhibitory concentration of I534D mutant were increased 35.7% and 48.1%, respectively. The agmatine production of the whole-cell bioconversion with AGM3 was increased by 19.3% than the AGM2. Finally, 45.26 g/L agmatine with the yield of 0.31 g/g glucose was achieved by one-step fermentation of the engineered C. crenatum with overexpression of speA I534D. Conclusions The engineered C. crenatum strain AGM3 in this work was proved as an efficient microbial cell factory for the industrial fermentative production of agmatine. Based on the insights from this work, further producing other valuable biochemicals derived from l-arginine by Corynebacterium crenatum is feasible.
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spelling doaj.art-01ae820c8f3e4223803c7741d754f4b62022-12-22T04:11:58ZengBMCMicrobial Cell Factories1475-28592022-01-0121111210.1186/s12934-022-01742-3High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylaseFengyu Yang0Jiayu Xu1Yichun Zhu2Yi Wang3Meijuan Xu4Zhiming Rao5Key Laboratory of Industrial Biotechnology of the Ministry of Education, School of Biotechnology, Jiangnan UniversityKey Laboratory of Industrial Biotechnology of the Ministry of Education, School of Biotechnology, Jiangnan UniversityKey Laboratory of Industrial Biotechnology of the Ministry of Education, School of Biotechnology, Jiangnan UniversityKey Laboratory of Industrial Biotechnology of the Ministry of Education, School of Biotechnology, Jiangnan UniversityKey Laboratory of Industrial Biotechnology of the Ministry of Education, School of Biotechnology, Jiangnan UniversityKey Laboratory of Industrial Biotechnology of the Ministry of Education, School of Biotechnology, Jiangnan UniversityAbstract Background Agmatine is a member of biogenic amines and is an important medicine which is widely used to regulate body balance and neuroprotective effects. At present, the industrial production of agmatine mainly depends on the chemical method, but it is often accompanied by problems including cumbersome processes, harsh reaction conditions, toxic substances production and heavy environmental pollution. Therefore, to tackle the above issues, arginine decarboxylase was overexpressed heterologously and rationally designed in Corynebacterium crenatum to produce agmatine from glucose by one-step fermentation. Results In this study, we report the development in the Generally Regarded as Safe (GRAS) l-arginine-overproducing C. crenatum for high-titer agmatine biosynthesis through overexpressing arginine decarboxylase based on metabolic engineering. Then, arginine decarboxylase was mutated to release feedback inhibition and improve catalytic activity. Subsequently, the specific enzyme activity and half-inhibitory concentration of I534D mutant were increased 35.7% and 48.1%, respectively. The agmatine production of the whole-cell bioconversion with AGM3 was increased by 19.3% than the AGM2. Finally, 45.26 g/L agmatine with the yield of 0.31 g/g glucose was achieved by one-step fermentation of the engineered C. crenatum with overexpression of speA I534D. Conclusions The engineered C. crenatum strain AGM3 in this work was proved as an efficient microbial cell factory for the industrial fermentative production of agmatine. Based on the insights from this work, further producing other valuable biochemicals derived from l-arginine by Corynebacterium crenatum is feasible.https://doi.org/10.1186/s12934-022-01742-3Corynebacterium crenatumAgmatineArginine decarboxylaseRational designFeedback inhibition
spellingShingle Fengyu Yang
Jiayu Xu
Yichun Zhu
Yi Wang
Meijuan Xu
Zhiming Rao
High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase
Microbial Cell Factories
Corynebacterium crenatum
Agmatine
Arginine decarboxylase
Rational design
Feedback inhibition
title High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase
title_full High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase
title_fullStr High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase
title_full_unstemmed High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase
title_short High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase
title_sort high level production of the agmatine in engineered corynebacterium crenatum with the inhibition releasing arginine decarboxylase
topic Corynebacterium crenatum
Agmatine
Arginine decarboxylase
Rational design
Feedback inhibition
url https://doi.org/10.1186/s12934-022-01742-3
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