Continuous biomanufacturing with microbes - upstream progresses and challenges.

Current biomanufacturing facilities are mainly built for batch or fed-batch operations, which are subject to low productivities and do not achieve the great bioconversion potential of the rewired cells generated via modern biotechnology. Continuous biomanufacturing should be the future directions for high-yield and low-cost manufacturing of various fermentation products. This review discusses the major challenges and the strategies for continuous biomanufacturing with microbes, which include minimizing contamination risk, enhancing genetic stability over a long-term continuous operation, achieving high product titer, rate, and yield simultaneously by decoupling cell growth from product formation, and using modeling approach to accelerate research and development of continuous biomanufacturing. New strain designs and process engineering strategies, including integration with artificial intelligence, are also discussed for intelligent and the next generation of continuous biomanufacturing.