Harnessing acetogenic bacteria for one-carbon valorization toward sustainable chemical production

Abstract

The pressing climate change issues have intensified the need for a rapid transition towards a bio-based circular carbon economy. Harnessing acetogenic bacteria as biocatalysts to convert C1 compounds such as CO₂, CO, formate, or methanol into value-added multicarbon chemicals is a promising solution for both carbon capture and utilization, enabling sustainable and green chemical production. Recent advances in the metabolic engineering of acetogens have expanded the range of commodity chemicals and biofuels produced from C1 compounds. However, producing energy-demanding high-value chemicals on an industrial scale from C1 substrates remains challenging because of the inherent energetic limitations of acetogenic bacteria. Therefore, overcoming this hurdle is necessary to scale up the acetogenic C1 conversion process and realize a circular carbon economy. This review overviews the acetogenic bacteria and their potential as sustainable and green chemical production platforms. Recent efforts to address these challenges have focused on enhancing the ATP and redox availability of acetogens to improve their energetics and conversion performances. Furthermore, promising technologies that leverage low-cost, sustainable energy sources such as electricity and light are discussed to improve the sustainability of the overall process. Finally, we review emerging technologies that accelerate the development of high-performance acetogenic bacteria suitable for industrial-scale production and address the economic sustainability of acetogenic C1 conversion. Overall, harnessing acetogenic bacteria for C1 valorization offers a promising route toward sustainable and green chemical production, aligning with the circular economy concept.

Fig. 1. The Wood–Ljungdahl pathway and energy conservation system in acetogens. Fdh, formate dehydrogenase; Fhs, formyl-THF synthetase; Fch, formyl-THF cyclohydrolase; Mthfd, methenyl-THF dehydrogenase; Mthfr, methylene-THF reductase; MT, methyltransferase; CODH/ACS, CO dehydrogenase/acetyl-CoA synthase; Pta, phosphotransacetylase; Ack, acetate kinase; [H], reducing equivalent ([H] = 1e⁻ + 1H⁺).

Fig. 2. Biosynthesis pathways of multicarbon chemicals converted from acetyl-CoA in wild-type and engineered acetogens. Abbreviations: CoA, coenzyme A; PHB, poly-3-hydroxybutyrate; Pfor, pyruvate:ferredoxin oxidoreductase; AlsS, acetolactate synthase; AlsD, acetolactate decarboxylase; Bdh, 2,3-butanediol dehydrogenase; Ldh, lactate dehydrogenase; Ldh/Etf, bifurcating Ldh; IlvC, ketol-acid reductoisomerase; IlvD, dihydroxy-acid dehydratase; KivD, ketoisovalerate decarboxalyse; Pta, phosphotransacetylase; Ack, acetate kinase; Aor, aldehyde:ferredoxin oxidoreductase; Aldh, aldehyde dehydrogenase; Adh, alcohol dehydrogenase; Aat, alcohol acetyltransferase; ThlA, thiolase; Hbd, 3-hydroxybutyryl-CoA dehydrogenase; Crt, crotonase; Bcd, butyryl-CoA dehydrogenase; Bcd/Etf, bifurcating Bcd; Ptb, phosphotransbutyrylase; Buk, butyrate kinase; Ptf, phosphotransferase; Fak, fatty acid kinase; Icm, isobutyryl-CoA mutase; CoAT, CoA transferase; PhaC, polyhydroxyalkanoate synthase; Adc, acetoacetate decarboxylase; Sadh, primary secondary alcohol dehydrogenase; Cit, citrate lyase; AcnB, aconitase; AceA, isocitrate lyase; GhrA, glyoxylate reductase; AldA, glycolaldehyde dehydrogenase; FucO, lactaldehyde reductase.

Fig. 3. Strategies to increase intracellular ATP availability in acetogens. (A) A hypothetical mechanism for additional ATP synthesis via energy-conserving electron acceptor DMSO proposed in M. thermoacetica. (B) Arginine deiminase pathway for substrate-level phosphorylation coupled ATP synthesis.

Fig. 4. Scheme of supplying redox power through electricity or light. (A) Microbial electrosynthesis by direct electron transfer or indirectly via H₂ generated from the cathode surface. (B) Acetogenic CO₂ conversion using light-driven energy sources.

Fig. 5. Emerging technologies for accelerating the development of acetogenic strains with high performance. (A) Adaptive laboratory evolution generates mutant strains that possess enhanced tolerance to substrates or improved production capability. (B) A systems biology approach serves as a guide for understanding and designing improved strains, with the aid of omics analysis and in silico modelling. (C) A synthetic biology approach, employing a design-build-test-learn (DBTL) cycle as a framework, supports the construction, screening and designing of strains with desired functionalities. The DBTL cycle can be automated and accelerated with high-throughput screening and construction workflows.