Activation-independent cyclization of monoterpenoids.
Gabriele Siedenburg,Dieter Jendrossek,Michael Breuer,Benjamin Juhl,Jürgen Pleiss,Miriam Seitz,Janosch Klebensberger,Bernhard Hauer +7 more
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TLDR
A novel terpene cyclase from Zymomonas mobilis (ZMO1548-Shc) is reported with the unique capability to cyclize citronellal to isopulegol and is the first biocatalyst with diphosphate-independent monoterpenoid cyclase activity.Abstract:
The biosynthesis of cyclic monoterpenes (C10) generally requires the cyclization of an activated linear precursor (geranyldiphosphate) by specific terpene cyclases. Cyclic triterpenes (C30), 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.read more
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Expanding the Enzyme Universe: Accessing Non‐Natural Reactions by Mechanism‐Guided Directed Evolution
TL;DR: An evolutionary approach to engineering enzymes to catalyze reactions not found in nature to create new catalysts is outlined, with an emphasis on reactions that do not have natural counterparts.
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Squalene hopene cyclases are protonases for stereoselective Brønsted acid catalysis
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Ausdehnung des Enzym‐Universums: Zugang zu nicht‐natürlichen Reaktionen durch mechanismusgeleitete, gerichtete Evolution
TL;DR: In this article, an evolutiven Ansatz zur Entwicklung von Enzymen beschreiben, die solche nicht-naturlichen Reaktionen katalysieren.
References
More filters
Journal ArticleDOI
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Andrej Sali,Tom L. Blundell +1 more
TL;DR: A comparative protein modelling method designed to find the most probable structure for a sequence given its alignment with related structures, which is automated and illustrated by the modelling of trypsin from two other serine proteinases.
Journal ArticleDOI
ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins.
TL;DR: The quality scores of a protein are displayed in the context of all known protein structures and problematic parts of a structure are shown and highlighted in a 3D molecule viewer in the ProSA-web service.
Journal Article
The structure and function
TL;DR: This stately book is to show how the various types of animals have solved the fundamental problems of life, and how their struc-ture is to be interpreted in terms of their functions and environment.
Journal ArticleDOI
A Fast Flexible Docking Method using an Incremental Construction Algorithm
TL;DR: This work presents an automatic method for docking organic ligands into protein binding sites that combines an appropriate model of the physico-chemical properties of the docked molecules with efficient methods for sampling the conformational space of the ligand.
Journal ArticleDOI
Plant terpenoid synthases: Molecular biology and phylogenetic analysis
TL;DR: This review focuses on the monoterpene, sesquiterpenes, and diterpene synthases of plant origin that use the corresponding C10, C15, and C20 prenyl diphosphates as substrates to generate the enormous diversity of carbon skeletons characteristic of the terpenoid family of natural products.
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