Heterologous Biosynthesis of Cotylenol and Concise Synthesis of Fusicoccane Diterpenoids

Fusicoccane diterpenoids have attracted intensive attention due to their complex structures as well as diverse biological activities. Here we report a novel strategy for the synthesis of cotylenol and other fusicoccane diterpenoids. By harnessing the biosynthetic pathways of brassicicenes and fusicoccins, cotylenol was produced in an engineered Aspergillus oryzae strain. We further achieved the concise synthesis of three fusicoccane diterpenoids, including alterbrassicicene E and brassicicenes A and R in 4 or 5 chemical steps from brassicicene I. Our strategy may facilitate the preparation of fusicoccane diterpenoids and their synthetic analogues for biological studies.