Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

97 Scopus Citations
View graph of relations

Author(s)

Detail(s)

Original languageEnglish
Pages (from-to)10962-10965
Journal / PublicationJournal of the American Chemical Society
Volume135
Issue number30
Online published18 Jul 2013
Publication statusPublished - 31 Jul 2013
Externally publishedYes

Abstract

Austinol, a fungal meroterpenoid derived from 3,5-dimethylorsellinic acid, has a unique chemical structure with a remarkable spiro-lactone ring system. Despite the recent identification of its biosynthetic gene cluster and targeted gene-deletion experiments, the process for the conversion of protoaustinoid A (2), the first tetracyclic biosynthetic intermediate, to the spiro-lactone preaustinoid A3 (7) has remained enigmatic. Here we report the mechanistic details of the enzyme-catalyzed, stereospecific spiro-lactone ring-forming reaction, which is catalyzed by a non-heme iron-dependent dioxygenase, AusE, along with two flavin monooxygenases, the 5′-hydroxylase AusB and the Baeyer-Villiger monooxygenase AusC. Remarkably, AusE is a multifunctional dioxygenase that is responsible for the iterative oxidation steps, including the oxidative spiro-ring-forming reaction, to produce the austinol scaffold.

Citation Format(s)

Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol biosynthesis. / Matsuda, Yudai; Awakawa, Takayoshi; Wakimoto, Toshiyuki et al.

In: Journal of the American Chemical Society, Vol. 135, No. 30, 31.07.2013, p. 10962-10965.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review