[논문]Functional cooperation of the glycine synthase-reductase and Wood–Ljungdahl pathways for autotrophic growth of Clostridium drakei

Song, Yoseb; Lee, Jin Soo; Shin, Jongoh; Lee, Gyu Min; Jin, Sangrak; Kang, Seulgi; Lee, Jung-Kul; Kim, Dong Rip; Lee, Eun Yeol; Kim, Sun Chang; Cho, Suhyung; Kim, Donghyuk; Cho, Byung-Kwan

doi:10.1073/pnas.1912289117

[해외논문] Functional cooperation of the glycine synthase-reductase and Wood–Ljungdahl pathways for autotrophic growth of Clostridium drakei 원문보기

Proceedings of the National Academy of Sciences of the United States of America, v.117 no.13, 2020년, pp.7516 - 7523

Song, Yoseb (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea) , Lee, Jin Soo , Shin, Jongoh (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea) , Lee, Gyu Min , Jin, Sangrak (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea) , Kang, Seulgi , Lee, Jung-Kul (School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology, 44919 Ulsan, Republic of Korea) , Kim, Dong Rip , Lee, Eun Yeol (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea) , Kim, Sun Chang , Cho, Suhyung (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 34141 Daejeon, Republic of Korea) , Kim, Donghyuk , Cho, Byung-Kwan (Department of Chemical Engineering, Konkuk University, 05029 Seoul, Republic of Korea)

Abstract ▼ AI-Helper

SignificanceDespite sharing the first four reactions, coutilization of the Wood–Ljungdahl pathway (WLP) with the glycine synthase-reductase pathway (GSRP) and reductive glycine pathway (RGP) to fix C1 compounds has remained unknown. In this study, using Clostridium drakei, we elucidated the role of the GSRP and RGP in the presence of the WLP, via a genome-scale metabolic model, RNA-seq, 13C isotope-based metabolite-tracing experiments, biochemical assays, and heterologous expression. Overall, the data suggested the pathways are functional under autotrophic conditions. Along with the WLP, GSRP and RGP convert CO2 to glycine and then to acetyl-phosphate and serine, which then obtain ATP by producing acetate and operate with limited reducing power. This is a unique coutilization of the pathways under autotrophic conditions in acetogens.Among CO2-fixing metabolic pathways in nature, the linear Wood–Ljungdahl pathway (WLP) in phylogenetically diverse acetate-forming acetogens comprises the most energetically efficient pathway, requires the least number of reactions, and converts CO2 to formate and then into acetyl-CoA. Despite two genes encoding glycine synthase being well-conserved in WLP gene clusters, the functional role of glycine synthase under autotrophic growth conditions has remained uncertain. Here, using the reconstructed genome-scale metabolic model iSL771 based on the completed genome sequence, transcriptomics, 13C isotope-based metabolite-tracing experiments, biochemical assays, and heterologous expression of the pathway in another acetogen, we discovered that the WLP and the glycine synthase pathway are functionally interconnected to fix CO2, subsequently converting CO2 into acetyl-CoA, acetyl-phosphate, and serine. Moreover, the functional cooperation of the pathways enhances CO2 consumption and cellular growth rates via bypassing reducing power required reactions for cellular metabolism during autotrophic growth of acetogens.

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