A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters
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 vita...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-04-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/21/4/517 |
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| author | Dominik M. Peter Bastian Vögeli Niña Socorro Cortina Tobias J. Erb |
| author_facet | Dominik M. Peter Bastian Vögeli Niña Socorro Cortina Tobias J. Erb |
| author_sort | Dominik M. Peter |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T09:08:31Z |
| format | Article |
| id | doaj.art-fbd7fd2f18374df98bddd3a37fb610cd |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T09:08:31Z |
| publishDate | 2016-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-fbd7fd2f18374df98bddd3a37fb610cd2022-12-22T01:13:34ZengMDPI AGMolecules1420-30492016-04-0121451710.3390/molecules21040517molecules21040517A Chemo-Enzymatic Road Map to the Synthesis of CoA EstersDominik M. Peter0Bastian Vögeli1Niña Socorro Cortina2Tobias J. Erb3Institute for Microbiology, Eidgenössische Technische Hochschule (ETH) Zürich, Vladimir-Prelog-Weg 4, CH-8093 Zürich, SwitzerlandBiochemistry & Synthetic Biology of Microbial Metabolism Group, Max-Planck-Institute for Terrestrial Microbiology, Karl-von-Frisch-Str. 10, D-35043 Marburg, GermanyBiochemistry & Synthetic Biology of Microbial Metabolism Group, Max-Planck-Institute for Terrestrial Microbiology, Karl-von-Frisch-Str. 10, D-35043 Marburg, GermanyBiochemistry & Synthetic Biology of Microbial Metabolism Group, Max-Planck-Institute for Terrestrial Microbiology, Karl-von-Frisch-Str. 10, D-35043 Marburg, GermanyCoenzyme 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.http://www.mdpi.com/1420-3049/21/4/517CoA-thioesteracylationacyl-CoA dehydrogenasesenzyme promiscuitysecondary metabolitespolyketide synthasenatural product biosynthesisbiocatalysisextender units |
| spellingShingle | Dominik M. Peter Bastian Vögeli Niña Socorro Cortina Tobias J. Erb A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters Molecules CoA-thioester acylation acyl-CoA dehydrogenases enzyme promiscuity secondary metabolites polyketide synthase natural product biosynthesis biocatalysis extender units |
| title | A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters |
| title_full | A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters |
| title_fullStr | A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters |
| title_full_unstemmed | A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters |
| title_short | A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters |
| title_sort | chemo enzymatic road map to the synthesis of coa esters |
| topic | CoA-thioester acylation acyl-CoA dehydrogenases enzyme promiscuity secondary metabolites polyketide synthase natural product biosynthesis biocatalysis extender units |
| url | http://www.mdpi.com/1420-3049/21/4/517 |
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