Enzymatic synthesis of an indole diterpene by an oxidosqualene cyclase: mechanistic, biosynthetic, and phylogenetic implications

Xiong, Quando B., Zhu, Xiuwen, Wilson, William K., Ganesan, A. and Matsuda, Seiichi P.T. (2003) Enzymatic synthesis of an indole diterpene by an oxidosqualene cyclase: mechanistic, biosynthetic, and phylogenetic implications. Journal of the American Chemical Society, 125 (30), 9002-9003. (doi:10.1021/ja036322v).

Abstract

Petromindole (1) is an unusual indole diterpene that bears a triterpene-like carbon skeleton, suggesting biogenesis from 3-(-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.

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