Journal ArticleDOI
An enzymatic [4+2] cyclization cascade creates the pentacyclic core of pyrroindomycins.
Zhenhua Tian,Peng Sun,Yan Yan,Zhuhua Wu,Qingfei Zheng,Shuaixiang Zhou,Hua Zhang,Futao Yu,Xinying Jia,Dandan Chen,Attila Mándi,Tibor Kurtán,Wen Liu +12 more
TLDR
An unprecedented enzymatic [4+2] cyclization cascade that has a central role in the biosynthesis of pyrroindomycins, which are pentacyclic spirotetramate natural products is reported and it is confirmed that homologs are functionally exchangeable.Abstract:
The [4+2] cycloaddition remains one of the most intriguing transformations in synthetic and natural products chemistry. In nature, however, there are remarkably few enzymes known to have this activity. We herein report an unprecedented enzymatic [4+2] cyclization cascade that has a central role in the biosynthesis of pyrroindomycins, which are pentacyclic spirotetramate natural products. Beginning with a linear intermediate that contains two pairs of 1,3-diene and alkene groups, the dedicated cyclases PyrE3 and PyrI4 act in tandem to catalyze the formation of two cyclohexene rings in the dialkyldecalin system and the tetramate spiro-conjugate of the molecules. The two cyclizations are completely enzyme dependent and proceed in a regio- and stereoselective manner to establish the enantiomerically pure pentacyclic core. Analysis of a related spirotetronate pathway confirms that homologs are functionally exchangeable, establishing the generality of these findings and explaining how nature creates diverse active molecules with similar rigid scaffolds.read more
Citations
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Journal ArticleDOI
Oxidative Cyclization in Natural Product Biosynthesis
TL;DR: This Review examines the different strategies used by nature to create new intra(inter)molecular bonds via redox chemistry, with an emphasis on the former.
Journal ArticleDOI
The Catalytic Mechanism of a Natural Diels–Alderase Revealed in Molecular Detail
Matthew J. Byrne,Nicholas R. Lees,Nicholas R. Lees,Li-Chen Han,Marc W. van der Kamp,Adrian J. Mulholland,James E. M. Stach,Christine L. Willis,Paul R. Race +8 more
TL;DR: This study provides compelling evidence for the existence of a natural enzyme evolved to catalyze a Diels-Alder reaction and shows how catalysis is achieved.
Journal ArticleDOI
Enzymatic Cascade Reactions in Biosynthesis.
TL;DR: Four types of enzymatic cascade reactions are discussed: those involving nucleophilic, electrophilic, pericyclic, and radical reactions, and two subtypes of enzymes that generate radical cascades exist at opposite ends of the oxygen abundance spectrum.
Journal ArticleDOI
Applications of OR/ECD/VCD to the structure elucidation of natural products
Attila Mándi,Tibor Kurtán +1 more
TL;DR: The principles and applicability of optical rotation, and electronic and vibrational circular dichroism aided by quantum chemical calculations are presented to determine absolute configuration and conformation through examples of stereochemical analysis of natural products with emphasis on the possibility of combined analysis and pitfalls for natural product chemists.
Journal ArticleDOI
Natural [4 + 2]-Cyclases
TL;DR: While mechanistic investigation of these enzymes is just beginning, recent studies have provided new insights with implications for understanding their biosynthetic roles, mechanisms of catalysis, and evolutionary origin.
References
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Journal ArticleDOI
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