Model-based driving mechanism analysis for butyric acid production in Clostridium tyrobutyricum
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Published:2022-06-25
Issue:1
Volume:15
Page:
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ISSN:2731-3654
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Container-title:Biotechnology for Biofuels and Bioproducts
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language:en
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Short-container-title:Biotechnol Biofuels
Author:
Feng Jun,Guo Xiaolong,Cai Feifei,Fu Hongxin,Wang Jufang
Abstract
Abstract
Background
Butyric acid, an essential C4 platform chemical, is widely used in food, pharmaceutical, and animal feed industries. Clostridium tyrobutyricum is the most promising microorganism for industrial bio-butyrate production. However, the metabolic driving mechanism for butyrate synthesis was still not profoundly studied.
Results
This study reports a first-generation genome-scale model (GEM) for C. tyrobutyricum, which provides a comprehensive and systematic analysis for the butyrate synthesis driving mechanisms. Based on the analysis in silico, an energy conversion system, which couples the proton efflux with butyryl-CoA transformation by two redox loops of ferredoxin, could be the main driving force for butyrate synthesis. For verifying the driving mechanism, a hydrogenase (HydA) expression was perturbed by inducible regulation and knockout. The results showed that HydA deficiency significantly improved the intracellular NADH/NAD+ rate, decreased acetate accumulation (63.6% in serum bottle and 58.1% in bioreactor), and improved the yield of butyrate (26.3% in serum bottle and 34.5% in bioreactor). It was in line with the expectation based on the energy conversion coupling driving mechanism.
Conclusions
This work show that the first-generation GEM and coupling metabolic analysis effectively promoted in-depth understanding of the metabolic driving mechanism in C. tyrobutyricum and provided a new insight for tuning metabolic flux direction in Clostridium chassis cells.
Funder
National Natural Science Foundation of China
National Natural Science Foundation of China,China
Science and Technology Planning Project of Guangdong Province of China
Publisher
Springer Science and Business Media LLC
Subject
Management, Monitoring, Policy and Law,Energy (miscellaneous),Applied Microbiology and Biotechnology,Renewable Energy, Sustainability and the Environment,Biotechnology
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