Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria

ABSTRACT Protein lysine acetylation, a prevalent posttranslational modification, regulates numerous crucial biological processes in cells. Nevertheless, how lysine acetylation interacts with other types of regulation to coordinate metabolism remains largely unknown owing to the complexity of the pro...

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Autores principales:	Lu Zhang, Yanqiang Liu, Ran Zhao, Can Zhang, Weihong Jiang, Yang Gu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	CO2 fixation gas-fermenting C. ljungdahlii interactive regulation lysine acetylation transcription factor Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2846fcf4d93445fd99c7cff720d77514
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spelling	oai:doaj.org-article:2846fcf4d93445fd99c7cff720d775142021-11-15T15:56:43ZInteractive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria10.1128/mBio.00650-202150-7511https://doaj.org/article/2846fcf4d93445fd99c7cff720d775142020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00650-20https://doaj.org/toc/2150-7511ABSTRACT Protein lysine acetylation, a prevalent posttranslational modification, regulates numerous crucial biological processes in cells. Nevertheless, how lysine acetylation interacts with other types of regulation to coordinate metabolism remains largely unknown owing to the complexity of the process. Here, using a representative gas-fermenting bacterium, Clostridium ljungdahlii, we revealed a novel regulatory mechanism that employs both the lysine acetylation and transcriptional regulation systems to interactively control CO2 fixation, a key biological process for utilizing this one-carbon gas. A dominant lysine acetyltransferase/deacetylase system, At2/Dat1, was identified and found to regulate FDH1 (formate dehydrogenase responsible for CO2 fixation) activity via a crucial acetylation site (lysine-29). Notably, the global transcription factor CcpA was also shown to be regulated by At2/Dat1; in turn, CcpA could directly control At2 expression, thus indicating an unreported interaction mode between the acetylation system and transcription factors. Moreover, CcpA was observed to negatively regulate FDH1 expression, which, when combined with At2/Dat1, leads to the collaborative regulation of this enzyme. Based on this concept, we reconstructed the regulatory network related to FDH1, realizing significantly increased CO2 utilization by C. ljungdahlii. IMPORTANCE Microbial CO2 fixation and conversion constitute a potential solution to both utilization of greenhouse gas or industrial waste gases and sustainable production of bulk chemicals and fuels. Autotrophic gas-fermenting bacteria play central roles in this bioprocess. This study provides new insights regarding the metabolic regulatory mechanisms underlying CO2 reduction in Clostridium ljungdahlii, a representative gas-fermenting bacterium. A critical formate dehydrogenase (FDH1) responsible for fixing CO2 and a dominant reversible lysine acetylation system, At2/Dat1, were identified. Furthermore, FDH1 was found to be interactively regulated by both the At2/Dat1 system and the global transcriptional factor CcpA, and the two regulatory systems are mutually restricted. Reconstruction of this multilevel metabolic regulatory module led to improved CO2 metabolism by C. ljungdahlii. These findings not only substantively expand our understanding but also provide a potentially useful metabolic engineering strategy for microbial carbon fixation.Lu ZhangYanqiang LiuRan ZhaoCan ZhangWeihong JiangYang GuAmerican Society for MicrobiologyarticleCO2 fixationgas-fermenting C. ljungdahliiinteractive regulationlysine acetylationtranscription factorMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	CO2 fixation gas-fermenting C. ljungdahlii interactive regulation lysine acetylation transcription factor Microbiology QR1-502
spellingShingle	CO2 fixation gas-fermenting C. ljungdahlii interactive regulation lysine acetylation transcription factor Microbiology QR1-502 Lu Zhang Yanqiang Liu Ran Zhao Can Zhang Weihong Jiang Yang Gu Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria
description	ABSTRACT Protein lysine acetylation, a prevalent posttranslational modification, regulates numerous crucial biological processes in cells. Nevertheless, how lysine acetylation interacts with other types of regulation to coordinate metabolism remains largely unknown owing to the complexity of the process. Here, using a representative gas-fermenting bacterium, Clostridium ljungdahlii, we revealed a novel regulatory mechanism that employs both the lysine acetylation and transcriptional regulation systems to interactively control CO2 fixation, a key biological process for utilizing this one-carbon gas. A dominant lysine acetyltransferase/deacetylase system, At2/Dat1, was identified and found to regulate FDH1 (formate dehydrogenase responsible for CO2 fixation) activity via a crucial acetylation site (lysine-29). Notably, the global transcription factor CcpA was also shown to be regulated by At2/Dat1; in turn, CcpA could directly control At2 expression, thus indicating an unreported interaction mode between the acetylation system and transcription factors. Moreover, CcpA was observed to negatively regulate FDH1 expression, which, when combined with At2/Dat1, leads to the collaborative regulation of this enzyme. Based on this concept, we reconstructed the regulatory network related to FDH1, realizing significantly increased CO2 utilization by C. ljungdahlii. IMPORTANCE Microbial CO2 fixation and conversion constitute a potential solution to both utilization of greenhouse gas or industrial waste gases and sustainable production of bulk chemicals and fuels. Autotrophic gas-fermenting bacteria play central roles in this bioprocess. This study provides new insights regarding the metabolic regulatory mechanisms underlying CO2 reduction in Clostridium ljungdahlii, a representative gas-fermenting bacterium. A critical formate dehydrogenase (FDH1) responsible for fixing CO2 and a dominant reversible lysine acetylation system, At2/Dat1, were identified. Furthermore, FDH1 was found to be interactively regulated by both the At2/Dat1 system and the global transcriptional factor CcpA, and the two regulatory systems are mutually restricted. Reconstruction of this multilevel metabolic regulatory module led to improved CO2 metabolism by C. ljungdahlii. These findings not only substantively expand our understanding but also provide a potentially useful metabolic engineering strategy for microbial carbon fixation.
format	article
author	Lu Zhang Yanqiang Liu Ran Zhao Can Zhang Weihong Jiang Yang Gu
author_facet	Lu Zhang Yanqiang Liu Ran Zhao Can Zhang Weihong Jiang Yang Gu
author_sort	Lu Zhang
title	Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria
title_short	Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria
title_full	Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria
title_fullStr	Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria
title_full_unstemmed	Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria
title_sort	interactive regulation of formate dehydrogenase during co<sub>2</sub> fixation in gas-fermenting bacteria
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/2846fcf4d93445fd99c7cff720d77514
work_keys_str_mv	AT luzhang interactiveregulationofformatedehydrogenaseduringcosub2subfixationingasfermentingbacteria AT yanqiangliu interactiveregulationofformatedehydrogenaseduringcosub2subfixationingasfermentingbacteria AT ranzhao interactiveregulationofformatedehydrogenaseduringcosub2subfixationingasfermentingbacteria AT canzhang interactiveregulationofformatedehydrogenaseduringcosub2subfixationingasfermentingbacteria AT weihongjiang interactiveregulationofformatedehydrogenaseduringcosub2subfixationingasfermentingbacteria AT yanggu interactiveregulationofformatedehydrogenaseduringcosub2subfixationingasfermentingbacteria
_version_	1718427140922277888

Interactive Regulation of Formate Dehydrogenase during CO<sub>2</sub> Fixation in Gas-Fermenting Bacteria

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