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A monodomain class II terpene cyclase assembles complex isoprenoid scaffolds.
Journal article

A monodomain class II terpene cyclase assembles complex isoprenoid scaffolds.

  • Moosmann P Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland.
  • Ecker F Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Chair of Biochemistry, Technische Universität München, Garching, Germany.
  • Leopold-Messer S Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland.
  • Cahn JKB Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland.
  • Dieterich CL Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland.
  • Groll M Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Chair of Biochemistry, Technische Universität München, Garching, Germany. michael.groll@tum.de.
  • Piel J Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland. jpiel@etz.ch.
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  • 2020-08-12
Published in:
  • Nature chemistry. - 2020
General Chemistry
General Chemical Engineering
English Class II terpene cyclases, such as oxidosqualene and squalene-hopene cyclases, catalyse some of the most complex polycyclization reactions. They minimally exhibit a β,γ-didomain architecture that has been evolutionarily repurposed in a wide range of terpene-processing enzymes and likely resulted from a fusion of unidentified monodomain proteins. Although single domain class I terpene cyclases have already been identified, the corresponding class II counterparts have not been previously reported. Here we present high-resolution X-ray structures of a monodomain class II cyclase, merosterolic acid synthase (MstE). With a minimalistic β-domain architecture, this cyanobacterial enzyme is able to construct four rings in cytotoxic meroterpenoids with a sterol-like topology. The structures with bound substrate, product, and inhibitor provide detailed snapshots of a cyclization mechanism largely governed by residues located in a noncanonical enzyme region. Our results complement the few known class II cyclase crystal structures, while also indicating that archaic monodomain cyclases might have already catalyzed complex reaction cascades.
Language
  • English
Open access status
closed
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Persistent URL
https://folia.unifr.ch/global/documents/137201
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