Engineering Acetogenic Bacteria for Efficient One-Carbon Utilization

Abstract

C1 gases, including carbon dioxide (CO2) and carbon monoxide (CO), are major contributors to climate crisis. Numerous studies have been conducted to fix and recycle C1 gases in order to solve this problem. Among them, the use of microorganisms as biocatalysts to convert C1 gases to value-added chemicals is a promising solution. Acetogenic bacteria (acetogens) have received attention as high-potential biocatalysts owing to their conserved Wood–Ljungdahl (WL) pathway, which fixes not only CO2 but also CO. Although some metabolites have been produced via C1 gas fermentation on an industrial scale, the conversion of C1 gases to produce various biochemicals by engineering acetogens has been limited. The energy limitation of acetogens is one of the challenges to overcome, as their metabolism operates at a thermodynamic limit, and the low solubility of gaseous substrates results in a limited supply of cellular energy. This review provides strategies for developing efficient platform strains for C1 gas conversion, focusing on engineering the WL pathway. Supplying liquid C1 substrates, which can be obtained from CO2, or electricity is introduced as a strategy to overcome the energy limitation. Future prospective approaches on engineering acetogens based on systems and synthetic biology approaches are also discussed.

Leveraging substrate flexibility and product selectivity of acetogens in two‐stage systems for chemical production

“…It is, therefore, possible to outline strategies integrating abiotic and biotic catalyses to harness their respective advantages, namely the high specificity and energetic efficiency of CO 2 hydrogenation, on one side, and the flexibility of the biological processes regarding the achievable products, on the other side. In this regard, strain optimization through genetic modifications may be necessary to steer the carbon and electron flow into the compound of interest and to prevent side‐products' formation (Bourgade et al, 2021 ; Lee et al, 2022 ). Notably, the flexibility of the abiotic/biotic two‐stage process benefits also of the fact that it is possible to divert methanol and formic acid intermediates to other, non‐biological uses.…”

“…Additionally, several studies focused on the development of efficient reactor configurations combining enhanced gas‐to‐liquid mass transfer with low power consumption (Asimakopoulos et al, 2018 ; Elisiario et al, 2022 ; Stoll et al, 2019 ; Takors et al, 2018 ). Over the past several years, synthetic biology approaches have been employed to develop acetogens in efficient platform strains for C 1 gas conversion, focusing in particular on the manipulation of metabolic fluxes aimed at the production of non‐native compounds (Bourgade et al, 2021 ; Lee et al, 2022 ). Intense process optimizations along with pilot‐ and demonstration‐plants operations addressed the at‐scale operability of the application of acetogens in gas fermentation processes (Fackler et al, 2021 ; Liew et al, 2022 ).…”

Model-driven approach for the production of butyrate from CO2/H2 by a novel co-culture of C. autoethanogenum and C. beijerinckii

“…Acetogens that grow autotrophically on these slightly soluble gases are energy limited and produce a constrained product spectrum and low product titers. This can be overcome by exploring alternative strategies, such as mixotrophic growth or co-cultivation (Lee et al, 2022 ).…”

Model-driven approach for the production of butyrate from CO2/H2by a novel co-culture ofC. autoethanogenumandC. beijerinckii

“…(10,11). However, alternative strategies are needed to overcome energy limitations of acetogens and the low solubility associated to C1 gases, which constrains the product spectrum and the product titres in the fermentation broth (12). Solventogenic clostridia naturally produce mixes of acetone, butanol and ethanol (ABE) (13), that have applications as solvents, by fermentation of sugars.…”

“…(10, 11). However, alternative strategies are needed to overcome energy limitations of acetogens and the low solubility associated to C1 gases, which constrains the product spectrum and the product titres in the fermentation broth (12).…”