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Complexity and Diversity Generation in the Biosynthesis of Fumiquinazoline-Related Peptidyl Alkaloids
Daojiang Yan1, Qibin Chen1, Jie Gao1
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing 100050 , P.R. China.
Abstract:
Fumiquinazolines are multicyclic peptidyl alkaloids where FAD-dependent oxidases are main tailing redox enzymes in their biosynthesis. Here, we characterized the use of an α-KG/Fe(II)-dependent dioxygenase (α-KGD) as a new strategy in Nature to increase structural complexity in fumiquinazolines biosynthesis by elucidating the concise three enzymes biosynthetic pathway of heptacyclical alanditrypinone (1). Further genome mining led to the discovery of additional gene cluster with α-KGD and trimodular NRPS as partner, which generates diverse fumiquinazolines.
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