Affiliations 

  • 1 Department of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan
  • 2 Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan
  • 3 National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan
  • 4 Department of Chemistry and Biochemistry, University of California, 607 Charles E. Young Drive East, Box 951569, Los Angeles, CA, 90095, USA
  • 5 Department of Chemical and Biomolecular Engineering and, Department of Chemistry and Biochemistry, University of California, 420 Westwood Plaza, Los Angeles, CA, 90095, USA
  • 6 School of Biosciences, The University of Nottingham Malaysia Campus, Jalan Broga, Selangor, 43500, Malaysia
  • 7 Department of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan. kenji55@u-shizuoka-ken.ac.jp
Chembiochem, 2015 Nov 2;16(16):2294-8.
PMID: 26360642 DOI: 10.1002/cbic.201500386

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.