Enzymatic synthesis of an indole diterpene by an oxidosqualene cyclase: mechanistic, biosynthetic, and phylogenetic implications.
Petromindole (1) is an unusual indole diterpene that bears a triterpene-like carbon skeleton, suggesting biogenesis from 3-(omega-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.
Xiong
Quanbo
Q
Department of Chemistry and Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
Zhu
Xiuwen
X
Wilson
William K
WK
Ganesan
A
A
Matsuda
Seiichi P T
SP
D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D004224:Diterpenes / Q000138:chemical synthesis / Q000378:metabolism*; D007211:Indoles / Q000138:chemical synthesis / Q000378:metabolism*; D019751:Intramolecular Transferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny
D004224:Diterpenes; D007211:Indoles; D019751:Intramolecular Transferases; C117114:lupeol synthase; C021924:lanosterol synthase