뉴스&공지 KAIST Graduate School of Engineering Biology

Growth-decoupled biomanufacturing platform for non-food feedstocks

Waste-derived one-carbon (C1) and two-carbon (C2) compounds are emerging as promising alternatives to conventional sugar-based feedstocks for biomanufacturing, owing to their low cost, wide availability, and sustainability. However, achieving commercially viable titer, rate, and yield from C1 and C2 substrates remains a fundamental challenge, as native bow-tie metabolic architectures of industrial host organisms inherently divert flux toward biomass and competing byproducts at the expense of target product synthesis. To address this, we argue that a paradigm shift is needed in how cellular metabolism is engineered for these feedstocks: transitioning from conventional engineering of natural metabolic networks to the development of synthetic, orthogonal pathways designed for superior carbon, energy, and enzyme efficiency. To realize this vision, our lab pursues three synergistic angles. First, we mine and engineer enzymes and construct synthetic metabolic pathways to enable efficient, orthogonal bioconversion of C1 and C2 substrates to value-added products. Second, we spatially isolate these pathways in membrane-bound compartments to prevent promiscuous host enzymes from diverting pathway intermediates. Third, we temporally decouple the production phase from the growth phase through dynamic downregulation of central metabolic flux, redirecting carbon and reducing equivalents toward product synthesis. Taken together, these efforts establish a generalizable framework for orthogonal bioconversion of waste C1 and C2 feedstocks. In this talk, I will share our ongoing progress in each of these three directions and discuss future research toward a sustainable bioeconomy built on C1 and C2 biomanufacturing.