Flavin-enabled Oxidative C-C Bond Cleavage and Rearrangement Reactions in the Biosynthesis of Novel Oxaspiro Angucycline Derivatives
Year: 2022
Type: preprint
Abstract: Flavin-enabled oxidative C-C Bond cleavages lead to fantastic structural alternations and are crucial for biological activity of many natural products. Here we report the discovery of novel atypical agucycline derivatives including spirocyclione A (1) which contains an unusual oxaspiro[5.5]undecane architecture and spirocyclione B (2) possessing an intriguing di-carboxylic substituted benzochromene scaffold by heterologous expression of a type II polyketide biosynthetic gene cluster. Biosynthesis studies demonstrated 1 and 2 are generated by sequential flavin-enabled C-C bond cleavage and rearrangement reactions where SpiH3 is responsible for the cleavage of C12a-C12b bond of early typical tetracyclic intermediate to form the oxaspiro structure of 1 and SpiH1, a new member of Baeyer-Villiger monooxygenases catalyzes the crucial cleavage of C12-C12a bond in 1 to give the ring-A opened product of 2. Our work reveals an unprecedented pattern of post-PKS modification on angucycline skeletons that contribute structural diversity and complexity to aromatic polyketides.
Source: Research Square
Language: English
Subfield: Applied Microbiology and Biotechnology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funders: Shandong University, National Natural Science Foundation of China, Chinese Academy of Sciences, Shanghai Jiao Tong University, Natural Science Foundation of Shandong Province, Polit National Laboratory for Marine Science and Technology, National Natural Science Foundation of China-Shandong Joint Fund, Institute of Microbiology, Chinese Academy of Sciences, Sanya Yazhou Bay Science and Technology City
Awards: G1241773277, G1571734419, G1623742816, G1743940349, G1919547914, G2296084301, G2379752129, G3945544845, G3983370572, G400842781, G4376543941, G4874168630, G5031234603, G5038598930, G5280824883, G6177706599, G6492539748, G6598208092, G6985915429, G7008525000, G7027777623, G7468457853, G8177304663, G8728835863, G8968108761, G95675335
OpenAlex ID: W4297894096