Synthetic Biology of Terpenoid and Flavonoid Natural Food Additives: Research Progress and Future Challenges

Food additives play an indispensable role in food processing, in which they improve taste, flavor, and appearance. Terpenoid and flavonoid natural food additives (NFAs), mostly derived from plants, are believed to be healthier and greener. However, limited supply and low yield result in high production costs. The development of synthetic biology technologies opens the door for the bioproduction of terpenoid and flavonoid NFAs. This account summarizes the biosynthetic routes of representative terpenoid and flavonoid NFAs, highlighting recent progress in the bioproduction of natural flavors, sweeteners, and pigments. Particularly, the frontier metabolic engineering strategies that aim to improve the production of terpenoid and flavonoid NFAs are also systematically summarized, including engineering the supply of the precursor, promoter engineering strategies, engineering cofactor supply, enzyme engineering, subcellular organelle engineering, biosensor-based dynamic regulation, and microbial consortia engineering. Finally, the prospects and challenges of synthetic biology for the production of NFAs are discussed.