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Communication

Enzymatic Synthesis of an Indole Diterpene by an Oxidosqualene Cyclase: Mechanistic, Biosynthetic, and Phylogenetic Implications

Supporting Info

Quanbo Xiong,^† Xiuwen Zhu,^§ William K. Wilson,^† A. Ganesan,*^§ and Seiichi P. T. Matsuda*^†;

Department of Chemistry and Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77005, and Department of Chemistry, University of Southampton, Southampton SO17 1BJ, UK

J. Am. Chem. Soc., 2003, 125 (30), pp 9002–9003

DOI: 10.1021/ja036322v

Publication Date (Web): July 8, 2003

†

Department of Biochemistry and Cell Biology, Rice University.

Department of Chemistry, University of Southampton.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

‖

Department of Chemistry, Rice University.

matsuda@rice.edu; ganesan@soton.ac.uk

Abstract

Petromindole (1) is an unusual indole diterpene that bears a triterpene-like carbon skeleton, suggesting biogenesis from 3-(ω-oxido-geranylgeranyl)indole (4). We found that lupeol synthase (LUP1) from Arabidopsis thaliana cyclizes 4 to 1. Chiral HPLC comparisons of racemic 1 (from biomimetic cyclization of N-pivaloyl-4) with the LUP1 product and authentic 1 established the absolute stereochemistry of petromindole (3S) as that of cyclic triterpenes. Quantum mechanical calculations and conformational analysis of intermediates in the cyclization of 4 to 1 indicated that petromindole biosynthesis differs fundamentally from that of other indole diterpenes. This analysis revealed that radarins also originate from cyclization of 4 but undergo a backbone rearrangement rather than annulation to indole. The combined results support our hypothesis that native fungal petromindole synthase evolved from a pentacyclic triterpene synthase distant from most other indole diterpene synthases.