Engineered microorganisms unlock a new era of diterpenoid biomanufacturing: recent advances and future perspectives

Diterpenoids are natural compounds composed of four isoprene units. They possess diverse biological activities and widespread applications in the cosmetics, food additives and pharmaceutical. With the rapid advancement of synthetic biology, the biomanufacturing of diterpenoids via microbial metabolism has witnessed substantial advancements. Microbial chassis such as Escherichia coli, Saccharomyces cerevisiae, Yarrowia lipolytica and Rhodosporidium toruloides, have been successfully engineered to enable efficient biosynthesis of these compounds, thereby demonstrating substantial potential for industrial-scale applications. In this review, the construction of diterpenoid biosynthetic pathways in microbial cell factories is summarized. The research progress and engineering strategies for efficient microbial synthesis of diterpenoids are discussed, and the key challenges and future directions facilitating the design of high-yield diterpenoid production platforms and their translation into industrial practice are explored.