Beyond Cell Factory: In Vitro Biotransformation (ivBT): A Paradigm-Shifting Biomanufacturing Platform

The paradigm of industrial biomanufacturing is shifting rapidly. Microbial fermentation mediated by cell factories is the dominant platform of biomanufacturing and has a history of thousands of years. However, their inherent properties, such as self-proliferation, cellular complexity, maintenance, and bioenergetic limits, could prevent them from being the best winner of biomanufacturing, especially for biocommodities and bioenergy. In this book chapter, we introduce a new concept of in vitro biotransformation (ivBT) as an emerging biomanufacturing platform that can surpass microbial cell factory. The development of ivBT is driven by the urgent great needs of food security and a new carbon-neutral energy society in the future. In theory, ivBT can have the theoretical yield and very high volumetric productivity and could have low-cost biomanufacturing costs. Furthermore, we highlight several representative applications, such as artificial photosynthesis for CO₂-to-starch synthesis, in vitro respiration that can produce hydrogen under anaerobic conditions and electricity under aerobic conditions, directed glycosidic bond rearrangement (i.e., ATP-free or low-ATP biotransformation of cellulose to starch), and healthy sugars. Industrial biomanufacturing of myo-inositol, D-tagatose, and cellulosic starch would wipe off any prejudice (e.g., costly enzymes and short lifetime) and demonstrate transformative potential of ivBT. ivBT would be a paradigm-shifting biomanufacturing platform because it is like a dimensional reduction attack that can simplify extremely complicated cell factories by decreasing their dimensions.