Yiwen Yu, Longqing Wang, Yan Zhang, Rui Zhang, Aamer Ali Shah, Chunjie Gong
Abstract Sclareol, a plant-derived diterpene, holds significant industrial value in perfumery, pharmaceuticals, and agriculture. Traditional production from Salvia sclarea or chemical synthesis has faced challenges such as low yield, high cost, and sustainability concerns. Recent advances in synthetic biology and metabolic engineering have enabled sclareol biosynthesis in microbial chassis cells. This Review systematically examines synthetic biology-driven strategies for improving sclareol production, with particular emphasis on microbial chassis engineering, metabolic pathway optimization, and enzyme engineering. Emerging approaches such as AI-assisted prediction, multiomics analysis, high-throughput screening, and intelligent fermentation technologies are also highlighted. Achievements and challenges in microbial sclareol biosynthesis are critically analyzed, and strategic priorities for future development are proposed. This paper provides a comprehensive reference for science and practice, aiming to advance the sustainable biomanufacturing of high-value plant-derived terpenoids.