Recent Advancements in the Biomanufacturing of Crocetin and Crocins: Key Enzymes and Metabolic Engineering

Crocetin and crocins are high-value apocarotenoids recognized for their role as food colorants as well as for their numerous industrial and therapeutic applications. Biotechnological platforms have the potential to replace traditional plant-based extraction of these compounds with a more sustainable approach. This review first introduced the catalytic characteristics of key enzymes involved in the biosynthetic pathway of crocetin and crocins, including carotenoid cleavage dioxygenases, aldehyde dehydrogenases, and uridine diphosphate glycosyltransferases. Next, we highlighted advanced metabolic engineering strategies aimed at enhancing crocetin and crocin production, such as increasing the pool of precursors and cofactors, protein mining and engineering, tuning protein expression, biosensor, genomic integration, and process optimization. Finally, the paper proposed potential strategies and tools associated with further boosting the heterologous production of crocetin and crocins to meet commercial-scale demands.