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A quantum chemical study of the omega-transaminase reaction mechanism
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
Stockholm University, Faculty of Science, Department of Organic Chemistry.
2015 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, no 31, 8453-8464 p.Article in journal (Refereed) Published
Abstract [en]

omega-Transaminases are valuable tools in biocatalysis due to their stereospecificity and their broad substrate range. In the present study, the reaction mechanism of Chromobacterium violaceum omega-transaminase is investigated by means of density functional theory calculations. A large active site model is designed based on the recent X-ray crystal structure. The detailed energy profile for the half-transamination of (S)-1-phenylethylamine to acetophenone is calculated and the involved transition states and intermediates are characterized. The model suggests that the amino substrate forms an external aldimine with the coenzyme pyridoxal-5'-phosphate (PLP), through geminal diamine intermediates. The external aldimine is then deprotonated in the rate-determining step, forming a planar quinonoid intermediate. A ketimine is then formed, after which a hemiaminal is produced by the addition of water. Subsequently, the ketone product is obtained together with pyridoxamine-5'-phosphate (PMP). In the studied half-transamination reaction the ketone product is kinetically favored. The mechanism presented here will be valuable to enhance rational and semi-rational design of engineered enzyme variants in the development of omega-transaminase chemistry.

Place, publisher, year, edition, pages
The Royal Society of Chemistry , 2015. Vol. 13, no 31, 8453-8464 p.
National Category
Organic Chemistry
URN: urn:nbn:se:su:diva-120490DOI: 10.1039/c5ob00690bISI: 000358733100011OAI: diva2:852851
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2015-09-10 Created: 2015-09-10 Last updated: 2016-10-05Bibliographically approved

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Engelmark Cassimjee, KarimManta, BiancaHimo, Fahmi
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