Biosynthesis of Terpenoid-Pyrrolobenzoxazine Hybrid Natural Product CJ-12662

Wei Cheng; Mengbin Chen; Masao Ohashi; Yi Tang

doi:10.1002/anie.202116928

Biosynthesis of Terpenoid-Pyrrolobenzoxazine Hybrid Natural Product CJ-12662

Angew Chem Int Ed Engl. 2022 Mar 14;61(12):e202116928. doi: 10.1002/anie.202116928. Epub 2022 Feb 3.

Authors

Wei Cheng^{1

2}, Mengbin Chen^{1

3}, Masao Ohashi¹, Yi Tang^{1

4}

Affiliations

¹ Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, USA.
² State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China.
³ Present address: Merck & Co, Inc., Rahway, NJ, USA.
⁴ Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.

Abstract

The fungal natural product CJ-12662 is a structurally complex terpene-amino acid hybrid, and is a potent anthelmintic compound. The biosynthetic pathway of CJ-12662 is elucidated based on metabolite analysis from heterologous expression. We demonstrate the terpene portion is derived from successive P450-catalyzed oxidations of amorpha-4,11-diene, while three flavin-dependent enzymes are involved in morphing the esterified tryptophan into a chlorinated pyrrolobenzoxazine, utilizing a cascaded [1,2]-Meisenheimer rearrangement.

Keywords: Amorpha-4,11-diene Synthase; Flavoenzymes; Fungal Natural Products; Pyrrolobenzoxazine; [1,2]-Meisenheimer Rearrangement.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Alkyl and Aryl Transferases*
Benzoxazines
Biological Products*
Pyrroles
Terpenes / chemistry

Substances

Benzoxazines
Biological Products
CJ 12662
Pyrroles
Terpenes
Alkyl and Aryl Transferases

Grants and funding

R35 GM118056/GM/NIGMS NIH HHS/United States