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Involvement of Lipocalin‐like CghA in Decalin‐Forming Stereoselective Intramolecular [4+2] Cycloaddition
Author(s) -
Sato Michio,
Yagishita Fumitoshi,
Mino Takashi,
Uchiyama Nahoko,
Patel Ashay,
Chooi YitHeng,
Goda Yukihiro,
Xu Wei,
Noguchi Hiroshi,
Yamamoto Tsuyoshi,
Hotta Kinya,
Houk Kendall N.,
Tang Yi,
Watanabe Kenji
Publication year - 2015
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500386
Subject(s) - decalin , stereoselectivity , cycloaddition , intramolecular force , chemistry , diastereomer , stereochemistry , natural product , biochemistry , catalysis
Understanding enzymatic Diels–Alder (DA) reactions that can form complex natural product scaffolds is of considerable interest. Sch 210972 1 , a potential anti‐HIV fungal natural product, contains a decalin core that is proposed to form through a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo ( 1 ) and a diastereomeric exo adduct of the proposed DA reaction. Complementation with cghA restored the sole formation of 1 . Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin‐like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1 .