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Molecules 2016, 21(4), 517; doi:10.3390/molecules21040517

A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters

1
Institute for Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, CH-8093 Zürich, Switzerland
2
Biochemistry & Synthetic Biology of Microbial Metabolism Group, Max-Planck-Institute for Terrestrial Microbiology, Karl-von-Frisch-Str. 10, D-35043 Marburg, Germany
These Authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Tobias A. M. Gulder
Received: 20 March 2016 / Revised: 11 April 2016 / Accepted: 15 April 2016 / Published: 20 April 2016
(This article belongs to the Special Issue Biosynthesis of Natural Products)
View Full-Text   |   Download PDF [1443 KB, uploaded 20 April 2016]   |  

Abstract

Coenzyme A (CoA) is a ubiquitous cofactor present in every known organism. The thioesters of CoA are core intermediates in many metabolic processes, such as the citric acid cycle, fatty acid biosynthesis and secondary metabolism, including polyketide biosynthesis. Synthesis of CoA-thioesters is vital for the study of CoA-dependent enzymes and pathways, but also as standards for metabolomics studies. In this work we systematically tested five chemo-enzymatic methods for the synthesis of the three most abundant acyl-CoA thioester classes in biology; saturated acyl-CoAs, α,β-unsaturated acyl-CoAs (i.e., enoyl-CoA derivatives), and α-carboxylated acyl-CoAs (i.e., malonyl-CoA derivatives). Additionally we report on the substrate promiscuity of three newly described acyl-CoA dehydrogenases that allow the simple conversion of acyl-CoAs into enoyl-CoAs. With these five methods, we synthesized 26 different CoA-thioesters with a yield of 40% or higher. The CoA esters produced range from short- to long-chain, include branched and α,β-unsaturated representatives as well as other functional groups. Based on our results we provide a general guideline to the optimal synthesis method of a given CoA-thioester in respect to its functional group(s) and the commercial availability of the precursor molecule. The proposed synthetic routes can be performed in small scale and do not require special chemical equipment, making them convenient also for biological laboratories. View Full-Text
Keywords: CoA-thioester; acylation; acyl-CoA dehydrogenases; enzyme promiscuity; secondary metabolites; polyketide synthase; natural product biosynthesis; biocatalysis; extender units CoA-thioester; acylation; acyl-CoA dehydrogenases; enzyme promiscuity; secondary metabolites; polyketide synthase; natural product biosynthesis; biocatalysis; extender units
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Peter, D.M.; Vögeli, B.; Cortina, N.S.; Erb, T.J. A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters. Molecules 2016, 21, 517.

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