How far do we need to go to upscale carbon elongation from bench- to industrial-scale?

Microbial carboxylate chain elongation (CCE) can convert biowastes into medium-chain fatty acids via the reverse β-oxidation pathway. Although the microbial mechanisms, metabolic pathways, and community ecology of CCE have been extensively investigated, the translation of CCE from bench-scale systems to industrial biorefinery applications remains unresolved, particularly when realistic biowastes are used instead of model substrates. This review classifies biowaste according to the biochemical compositions of carbohydrate, lignocellulosic, protein, and lipid to evaluate their compatibility with CCE. The required pretreatment strategies of biochemical compositions are discussed before secondary fermentation. We further discuss scale-dependent constraints associated with gas-liquid mass transfer, pH control, biomass retention, and product recovery. Thermodynamic analysis indicates that the responses of CCE and competing reactions to gas composition depend on substrate. Decoupling hydraulic retention time and solids retention time through biomass retention may facilitate stable continuous operation, although flux, fouling, and cost of membrane remain to be further investigated. This review proposes a conceptual integrated biorefinery framework for CCE from biowaste, and emphasizes that the industrial applicability should be evaluated using carbon recovery, productivity, energy and chemical demand, process stability, greenhouse-gas mitigation, and product-recovery efficiency.