Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• .21.111 Abstract A novel strategy for the synthesis of fusicoccane diterpenoids is reported. 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. This strategy lays the foundation for the preparation of fusicoccane diterpenoids and their analogues for biological studies. Keywords: cotylenol; fusicoccane diterpenoids; heterologous

• by its natural source, Cladosporium sp. 501-7W, due to the loss of its ability to proliferate during preservation [17]. The important biological activities and complex structures of fusicoccane diterpenoids have inspired several total syntheses, which range between 15 and 29 steps [18][19][20][21][22

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• cyclooctatin biosynthetic gene cluster in particular the TPS CotB2 from the soil bacterium Streptomyces melanosporofaciens MI614-43F2 (Figure 1) [31]. Cyclooctatin 5, with its distinct 5–8–5 ring motif, belongs to the fusicoccane diterpenoids that encompass a wide range of bioactivities, such as bacteriostatic