Volatile fatty acids as sustainable precursors for bioproduction: advances in pathway engineering, and bioprocess...

Substantial efforts have been dedicated to exploring alternative substrates for producing bioenergy and bioproducts, including exploring Volatile Fatty Acids (VFAs) as a promising carbon source. VFAs are short-chain organic acids with carbon chains ranging from C2 to C6. Advancements in biotechnology have enabled the metabolic engineering of microbial producers to convert VFAs into high-value biochemicals. Optimizing bioprocess parameters is as critical as genetic engineering for ensuring efficient substrate utilization and synthesis of desired product. This review provides a comprehensive summary of strategies for the utilization of VFAs as substrates for the bioproduction of a wide range of chemicals. Main topics cover mechanisms for VFA uptake and metabolism; challenges faced in VFA utilization, including toxicity, mixture complexity, and process integration; bioprocess strategies such as co-culture, feast-famine regimes, feeding techniques, and process optimization to enhance VFA valorization; and integrative electrochemical conversion with metabolic engineering approaches to improve efficiency in VFA upcycling. Overall, the review underscores the importance of advancing bioprocess and genetic strategies to unlock the full potential of VFAs for sustainable bioproduction.