Activation-independent cyclization of monoterpenoids

Appl Environ Microbiol. 2012 Feb;78(4):1055-62. doi: 10.1128/AEM.07059-11. Epub 2011 Dec 9.

Abstract

The biosynthesis of cyclic monoterpenes (C(10)) generally requires the cyclization of an activated linear precursor (geranyldiphosphate) by specific terpene cyclases. Cyclic triterpenes (C(30)), on the other hand, originate from the linear precursor squalene by the action of squalene-hopene cyclases (SHCs) or oxidosqualene cyclases (OSCs). Here, we report a novel terpene cyclase from Zymomonas mobilis (ZMO1548-Shc) with the unique capability to cyclize citronellal to isopulegol. To our knowledge, ZMO1548-Shc is the first biocatalyst with diphosphate-independent monoterpenoid cyclase activity. A combinatorial approach using site-directed mutagenesis and modeling of the active site with a bound substrate revealed that the cyclization of citronellal proceeds via a different mechanism than that of the cyclization of squalene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclic Monoterpenes
  • Aldehydes / metabolism*
  • Catalytic Domain
  • Cyclization
  • Cyclohexane Monoterpenes
  • Enzymes / genetics
  • Enzymes / metabolism*
  • Models, Molecular
  • Monoterpenes / metabolism*
  • Mutagenesis, Site-Directed
  • Terpenes / metabolism*
  • Zymomonas / enzymology*
  • Zymomonas / metabolism*

Substances

  • Acyclic Monoterpenes
  • Aldehydes
  • Cyclohexane Monoterpenes
  • Enzymes
  • Monoterpenes
  • Terpenes
  • isopulegol
  • citronellal