Oxyfunctionalization of nonsteroidal anti‐inflammatory drugs by filamentous‐fungi

Aims We aimed to expand the microbial biocatalyst platform to generate essential oxyfunctionalized standards for pharmaceutical, toxicological and environmental research. In particular, we examined the production of oxyfunctionalized nonsteroidal anti‐inflammatory drugs (NSAIDs) by filamentous‐fungi...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of applied microbiology Vol. 127; no. 3; pp. 724 - 738
Main Authors:	Klenk, J.M., Kontny, L.H., Escobedo‐Hinojosa, W., Nebel, B.A., Hauer, B.
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-09-2019
Subjects:	Anti-Inflammatory Agents, Non-Steroidal - metabolism Basidiomycota - metabolism Beauveria bassiana Biodegradation biotechnology Cytochrome Cytochrome P-450 Enzyme System - metabolism Cytochrome P450 Cytochromes P450 Diclofenac Diclofenac - metabolism Drugs environmental Environmental research Fungi Fungi - metabolism Ibuprofen Ibuprofen - metabolism Inflammation Intermediates Mefenamic acid Mefenamic Acid - metabolism Metabolism Metabolites Microorganisms Mucor - metabolism Naproxen Naproxen - metabolism Nonsteroidal anti-inflammatory drugs oxidation Pharmaceutical industry Pharmaceuticals Pharmacodynamics Pharmacology Proteomics Substrates oxidation biotechnology environmental pharmaceuticals fungi
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Aims We aimed to expand the microbial biocatalyst platform to generate essential oxyfunctionalized standards for pharmaceutical, toxicological and environmental research. In particular, we examined the production of oxyfunctionalized nonsteroidal anti‐inflammatory drugs (NSAIDs) by filamentous‐fungi. Methods and Results Four NSAIDs; diclofenac, ibuprofen, naproxen and mefenamic acid were used as substrates for oxyfunctionalization in a biocatalytic process involving three filamentous‐fungi strains; Beauveria bassiana, Clitocybe nebularis and Mucor hiemalis. Oxyfunctionalized metabolites that are major degradation intermediates formed by Cytochrome P450 monooxygenases in human metabolism were produced in isolated yields of up to 99% using 1 g l−1 of substrate. In addition, a novel compound, 3′,4′‐dihydroxydiclofenac, was produced by B. bassiana. Proteomic analysis identified CYP548A5 that might be responsible for diclofenac oxyfunctionalization in B. bassiana. Conclusions Efficient fungi catalysed oxyfunctionalization was achieved when using NSAIDs as substrates. High purities and isolated yields of the produced metabolites were achieved. Significance and Impact of the Study The lack of current efficient synthetic strategies for oxyfunctionalization of NSAIDs is a bottleneck to perform pharmacokinetic, pharmacodynamic and toxicological analysis for the pharmaceutical industry. Additionally, oxyfunctionalized derivatives are needed for tracking the fate and impact of such metabolites in the environment. Herein, we described a fungi catalysed process that surpasses previously reported strategies in terms of efficiency, to synthesize oxyfunctionalized NSAIDs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1364-5072 1365-2672
DOI:	10.1111/jam.14342