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An Intermolecular hetero-Diels−Alderase in the Biosynthesis of Fungal Meroterpenoids was Discovered and Characterized

Time:2019-9-11 Source: Read:181

 

A paper entitled “Enzymatic Intermolecular Hetero-Diels−Alder Reaction in the Biosynthesis of Tropolonic Sesquiterpenes” was recently published online in the Journal of the American Chemical Society (JACS), one of the top journals in the field of Chemistry. The research leading by Prof. Youcai Hu from the State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, CAMS, cooperated with Prof. K. N. Houk from UCLA reported the discovery and characterization of an intermolecular hetero-Diels-Alderase in the biosynthesis of fungal meroterpenoids.

Diels-Alder reactions are among the most powerful synthetic transformations to construct complex natural products. Despite that increasing number of enzymatic intramolecular Diels-Alder reactions have been discovered, natural intermolecular Diels-Alderases are rarely descripted. This paper reported an intermolecular hetero-Diels-Alder reaction in the biosynthesis of tropolonic sesquiterpenes and biochemically characterized EupfF as the first intermolecular hetero-Diels-Alderase from fungi.  EupfF was found to catalyze the dehydration of a hydroxymethyl containing tropolone (5) to generate a reactive tropolone o-quinone methide (6) and further stereo-selectively control the subsequent intermolecular hetero-Diels-Alder reaction with 1E,4E,8Z-humulenol (8) to produce enantiomerically pure neosetophomone B (1). This discovery expands the collection of increasing DAases from fungi and opens a new strategy for mining and combinational biosynthesis of tropolone-sesquiterpenes.

 

This work was financially supported by the CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2017-I2M-4-004; 2018-I2M-3-005) and the Drug Innovation Major Project (2018ZX09711001-006). Prof. Youcai Hu and Prof. K. N. Houk (from UCLA) are the co-corresponding authors, and both Dr. Qibin Chen and Dr. Jie Gao from Hu’s group are the co-first authors.

Full text links: https://pubs.acs.org/doi/10.1021/jacs.9b06592

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