C2/C1 Carbon–Redox Integration for Low-Carbon Production in Yarrowia lipolytica

Abstract

Low-carbon production requires feedstock platforms capable of connecting waste-carbon and CO2-derived intermediates with microbial production while allowing structural carbon supply and reducing-power delivery to be tuned independently. This perspective proposes C2/C1 carbon–redox integration as an emerging strategy for Yarrowia lipolytica bioproducts. Acetate is positioned as a C2 structural-carbon input for acetyl-CoA-dependent metabolism. Formate is evaluated mainly as a soluble C1 input that supports redox balance and carboxylation through FDH-driven NADH generation and CO2/HCO3-linked metabolism. Acetate is the more established C2 input for product formation in Y. lipolytica. In the other hand, formate remains a more specialized C1 intensification input for pathways constrained by redox balance or carboxylation demand. However, industrial translation is still limited by weak-acid toxicity, pH control, salt accumulation, oxygen-transfer demand, NADH/NADPH imbalance, and feedstock purity. In addition, side-by-side benchmarking against C6 substrates and other low-carbon feedstocks. Thus, future studies should move from empirical co-feeding toward quantitative carbon–electron matching, process control, and integrated techno-economic and life-cycle validation.