Abstract
Enhancing product efflux is crucial in improving fermentative bioproduction. Despite advancements in metabolic engineering guided by the design-build-test-learn cycle, membrane transport engineering of product efflux remains underdeveloped, limiting the efficient production of target chemicals. This review explores the historical findings on product efflux, regardless of passive or active transport, in fermentation engineering, focusing on Corynebacterium species, and highlights the potential of multidrug transporters as valuable screening sources for efflux improvement. Furthermore, the review emphasizes the importance of understanding the machinery of efflux transporters to optimize their functionality. Molecular dynamics simulations are a promising tool for exploring novel strategies to advance fermentation-related processes. These insights provide a framework for overcoming current challenges in membrane transport engineering of product efflux and improving industrial-scale bioproduction. KEY POINTS: • Review of strategies to enhance product efflux in Corynebacterium species. • Multidrug transporters are key tools for optimizing metabolite efflux. • Efflux transporter mechanisms analyzed to improve microbial productivity. • Molecular dynamics simulations employed for understanding transporter mechanisms.