Involvement of Lipocalin‐like CghA in Decalin‐Forming Stereoselective Intramolecular [4+2] Cycloaddition. Issue 16 (2nd October 2015)

• Record Type: Journal Article
• Authors: Sato, Michio; Yagishita, Fumitoshi; Mino, Takashi; Uchiyama, Nahoko; Patel, Ashay; Chooi, Yit‐Heng; Goda, Yukihiro; Xu, Wei; Noguchi, Hiroshi; Yamamoto, Tsuyoshi; Hotta, Kinya; Houk, Kendall N.; Tang, Yi; Watanabe, Kenji
• Is Part Of: Chembiochem. Volume 16:Issue 16(2015)
• Page Start: 2294
• Page End: 2298
• Publication Date: 2015-10-02
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201500386
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Understanding enzymatic Diels–Alder (DA) reactions that can form complex natural product scaffolds is of considerable interest. Sch 210972 <bold>1</bold>, 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 <bold>1</bold> and heterologously reconstituted the biosynthetic pathway in <italic>Aspergillus nidulans</italic> to characterize the enzymes involved. Most notably, deletion of <italic>cghA</italic> resulted in a loss of stereoselective decalin core formation, yielding both an <italic>endo</italic> (<bold>1</bold>) and a diastereomeric <italic>exo</italic> adduct of the proposed DA reaction. Complementation with <italic>cghA</italic> restored the sole formation of <bold>1</bold>. 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 <bold>1</bold>.</p> </abstract>