Functional cooperation of the glycine synthasereductase and Wood–Ljungdahl pathways for autotrophic growth of Clostridium drakei

• Published in: Proceedings of the National Academy of Sciences - PNAS 2020-03, Vol.117 (13), p.7516-7523
• Main Authors: 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
• Format: Article
• Language: English
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1912289117

Among CO₂-fixing metabolic pathways in nature, the linear Wood– Ljungdahl pathway (WLP) in phylogenetically diverse acetateforming 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 genomescale 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.