Functional cooperation of the glycine synthase-reductase and Wood–Ljungdahl pathways for autotrophic growth of <i>Clostridium drakei</i>
Yoseb Song, Jin Soo Lee, Jongoh Shin, Gyu Min Lee, Sangrak Jin, Seulgi Kang, Jung-Kul Lee, Dong Rip Kim, Eun Yeol Lee, Sun Chang Kim, Suhyung Cho, Donghyuk Kim, Byung‐Kwan Cho
Abstract
Among CO 2 -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 CO 2 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 i SL771 based on the completed genome sequence, transcriptomics, 13 C 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 CO 2 , subsequently converting CO 2 into acetyl-CoA, acetyl-phosphate, and serine. Moreover, the functional cooperation of the pathways enhances CO 2 consumption and cellular growth rates via bypassing reducing power required reactions for cellular metabolism during autotrophic growth of acetogens.