Raw materials for production of chemicals and energy are classified as either non-renewable or renewable. Non-renewable feedstocks, such as petroleum, natural gas, and coal, account for over 85% of global energy use. However, these sources cannot be readily replenished, and the production of chemicals from this route results in the emission of greenhouse gases. The development of sustainable strategies is critical to addressing challenges associated with industrial chemical production from fossil fuels. Such a strategy would prioritize the exploitation of abundant and renewable feedstocks while minimizing greenhouse gas emissions and environmental impacts. Renewable feedstocks derived from plants represent a sustainable and lower carbon emission alternative. However, this approach places the food industry in direct competition with the chemical industry, in addition to requiring intensive preprocessing steps in order to utilize every aspect of this biomass for chemical production. Direct microbial utilization of CH4 and CO2 presents a more sustainable and green approach for commercial chemical production. However, microbes metabolizing methane and carbon dioxide require specific conditions for optimal growth and metabolic activity. C4-dicarboxylate compounds, such as fumarate, succinate, malate, and aspartate, present another avenue for microbial growth but are not readily available. Their structural similarity to citric acid cycle-related metabolites positions them as prime candidates for microbial assimilation. This study presents acetylene dicarboxylate (ADCA), an unnatural C4-dicarboxylate derivable from methane and carbon dioxide, as a potential alternate feedstock. This research provides insight into microbial growth on acetylene dicarboxylate as the sole carbon source for the bioproduction of chemicals. We employ a multi-omic approach to elucidate the adaptation mechanism to the acetylenic carbon source, integrating comparative genomics, transcriptomics, and the analysis of excreted metabolites. These findings highlight the capacity of E. coli to assimilate and utilize acetylene dicarboxylate as the sole carbon source and identify putative genes responsible for ADCA utilization. We further demonstrate the bioconversion of ADCA to lactate (a commodity chemical) and shikimic acid (precursor for a pharmaceutical agent), offering a promising proof of concept for this novel feedstock as a sustainable and decarbonization approach in microbial biotechnology.
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