Rieske Oxygenase-Catalyzed Oxidative Late-Stage Functionalization during Complex Antifungal Polyketide Biosynthesis
Florian M Guth1, Frederick Lindner1, Simon Rydzek1
1Professur für Organische Chemie (Lebensmittelchemie), Fakultät für Biologie, Chemie und Geowissenschaften, Department of Chemistry, Universität Bayreuth, 95447 Bayreuth, Germany.
Abstract:
Rieske oxygenases (ROs) from natural product biosynthetic pathways are a poorly studied group of enzymes with significant potential as oxidative functionalization biocatalysts. A study on the ROs JerL, JerP, and AmbP from the biosynthetic pathways of jerangolid A and ambruticin VS-3 is described. Their activity was successfully reconstituted using whole-cell bioconversion systems coexpressing the ROs and their respective natural flavin-dependent reductase (FDR) partners. Feeding authentic biosynthetic intermediates and synthetic surrogates to these strains confirmed the involvement of the ROs in hydroxymethylpyrone and dihydropyran formation and revealed crucial information about the RO's substrate specificity. The pronounced dependence of JerL and JerP on the presence of a methylenolether allowed the precise temporal assignment of RO catalysis to the ultimate steps of jerangolid biosynthesis. JerP and AmbP stand out among the biosynthetic ROs studied so far for their ability to catalyze clean tetrahydropyran desaturation without further functionalizing the formed electron-rich double bonds. This work highlights the remarkable ability of ROs to highly selectively oxidize complex molecular scaffolds.
More Related Videos
08:31Anaerobic Protein Purification and Kinetic Analysis via Oxygen Electrode for Studying DesB Dioxygenase Activity and Inhibition
Published on: October 3, 2018
12:08Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
Published on: March 18, 2012
Related Concept Videos
Reactions of Aldehydes and Ketones: Baeyer–Villiger Oxidation
The carbonyl center is...
Oxidation of Alkenes: Anti Dihydroxylation with Peroxy Acids
Oxidative Cleavage of Alkenes: Ozonolysis
Ozone is a symmetrical bent molecule stabilized by a resonance structure.
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
Phase I Oxidative Reactions: Overview
Aldol Condensation with β-Diesters: Knoevenagel Condensation
