Biosynthesis of AS2077715 and Funiculosin: Pathway Reconstitution and Identification of Enzymes that Form the All- cis Cyclopentanetetraol Moiety

Yalong Zhang; Eun Bin Go; Bruno Perlatti; Lin Wu; Gerald F Bills; Masao Ohashi; Yi Tang

doi:10.1021/jacs.3c01681

Biosynthesis of AS2077715 and Funiculosin: Pathway Reconstitution and Identification of Enzymes that Form the All- cis Cyclopentanetetraol Moiety

J Am Chem Soc. 2023 Mar 29;145(12):6643-6647. doi: 10.1021/jacs.3c01681. Epub 2023 Mar 15.

Authors

Yalong Zhang¹, Eun Bin Go², Bruno Perlatti^{2

3}, Lin Wu¹, Gerald F Bills³, Masao Ohashi¹, Yi Tang^{1

2}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, University of California Los Angeles, Los Angeles, California 90095, United States.
² Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California 90095, United States.
³ Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas 77054, United States.

Abstract

The complete biosynthetic pathways of the potent antifungals AS2077715 (1) and funiculosin (2) are reconstituted and characterized. A five-enzyme cascade, including a multifunctional flavin-dependent monooxygenease and a repurposed O-methyltransferase, is involved to perform the dearomatization, stereoselective ring contraction, and redox transformations to morph a hydroxyphenyl-containing precursor into the unusual all-cis cyclopentanetetraol moiety.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Antifungal Agents*
Oxidation-Reduction

Substances

Antifungal Agents

Grants and funding

R35 GM118056/GM/NIGMS NIH HHS/United States