Regio- and Stereoselective Intermolecular Oxidative Phenol Coupling in Kotanin Biosynthesis by Aspergillus Niger

The intermolecular, regio‐ and stereoselective phenol coupling for the biosynthesis of the bicoumarin kotanin in Aspergillus niger has been investigated. Feeding experiments with singly and doubly 13C‐labeled monomeric precursors clearly proved that it is not the coumarin siderin but its hydroxy der...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2007-03, Vol.8 (5), p.521-529
Main Authors: Hüttel, Wolfgang, Müller, Michael
Format: Article
Language:English
Subjects:
Aspergillus niger - metabolism
atropisomerism
biaryls
Chromatography, High Pressure Liquid
Chromatography, Thin Layer
Circular Dichroism
coumarins
Coumarins - chemistry
filamentous fungi
isotopic labeling
Magnetic Resonance Spectroscopy
Methylation
Models, Chemical
Oxygen - chemistry
Phenol - chemistry
Stereoisomerism
Umbelliferones - chemistry
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Summary:The intermolecular, regio‐ and stereoselective phenol coupling for the biosynthesis of the bicoumarin kotanin in Aspergillus niger has been investigated. Feeding experiments with singly and doubly 13C‐labeled monomeric precursors clearly proved that it is not the coumarin siderin but its hydroxy derivative, demethylsiderin, that undergoes phenol coupling. However, siderin is demethylated regioselectively to demethylsiderin and it is the latter that is coupled to the corresponding dehydrodimer, orlandin. The product is subsequently O‐methylated in a stepwise fashion to demethylkotanin and kotanin. Crude extracts were analysed by HPLC with chemically synthesized bicoumarins as reference compounds. This and a stereochemical analysis of the isolated bicoumarins revealed that A. niger produces exclusively the (P)‐atropisomers of the three 8,8′‐bicoumarins, kotanin, demethylkotanin, and orlandin. The absence of other monomeric or dimeric coumarins strongly suggests an intermolecular, regio‐ and stereoselective mode for the phenol‐coupling step. The right (or left) way round. The highly selective intermolecular oxidative phenol‐coupling step in the biosynthesis of the bicoumarin kotanin was discovered by using a series of feeding experiments with chemically synthesized, 13C‐labeled monomeric precursors. These results offer new insights into the enzymatic basis for the regio‐ and stereoselective, intermolecular phenol coupling.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.200600434