An enzymatic platform for the synthesis of isoprenoid precursors.
The isoprenoid family of compounds is estimated to contain ∼ 65,000 unique structures including medicines, fragrances, and biofuels. Due to their structural complexity, many isoprenoids can only be obtained by extraction from natural sources, an inherently risky and costly process. Consequently, the...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4143292?pdf=render |
| _version_ | 1811279311421833216 |
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| author | Sofia B Rodriguez Thomas S Leyh |
| author_facet | Sofia B Rodriguez Thomas S Leyh |
| author_sort | Sofia B Rodriguez |
| collection | DOAJ |
| description | The isoprenoid family of compounds is estimated to contain ∼ 65,000 unique structures including medicines, fragrances, and biofuels. Due to their structural complexity, many isoprenoids can only be obtained by extraction from natural sources, an inherently risky and costly process. Consequently, the biotechnology industry is attempting to genetically engineer microorganisms that can produce isoprenoid-based drugs and fuels on a commercial scale. Isoprenoid backbones are constructed from two, five-carbon building blocks, isopentenyl 5-pyrophosphate and dimethylallyl 5-pyrophosphate, which are end-products of either the mevalonate or non-mevalonate pathways. By linking the HMG-CoA reductase pathway (which produces mevalonate) to the mevalonate pathway, these building block can be synthesized enzymatically from acetate, ATP, NAD(P)H and CoA. Here, the enzymes in these pathways are used to produce pathway intermediates and end-products in single-pot reactions and in remarkably high yield, ∼ 85%. A strategy for the regio-specific incorporation of isotopes into isoprenoid backbones is developed and used to synthesize a series of isotopomers of diphosphomevalonate, the immediate end-product of the mevalonate pathway. The enzymatic system is shown to be robust and capable of producing quantities of product in aqueous solutions that meet or exceed the highest levels achieved using genetically engineered organisms in high-density fermentation. |
| first_indexed | 2024-04-13T00:52:25Z |
| format | Article |
| id | doaj.art-9d81551835f74dd796d1dae7d61f181e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T00:52:25Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9d81551835f74dd796d1dae7d61f181e2022-12-22T03:09:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10559410.1371/journal.pone.0105594An enzymatic platform for the synthesis of isoprenoid precursors.Sofia B RodriguezThomas S LeyhThe isoprenoid family of compounds is estimated to contain ∼ 65,000 unique structures including medicines, fragrances, and biofuels. Due to their structural complexity, many isoprenoids can only be obtained by extraction from natural sources, an inherently risky and costly process. Consequently, the biotechnology industry is attempting to genetically engineer microorganisms that can produce isoprenoid-based drugs and fuels on a commercial scale. Isoprenoid backbones are constructed from two, five-carbon building blocks, isopentenyl 5-pyrophosphate and dimethylallyl 5-pyrophosphate, which are end-products of either the mevalonate or non-mevalonate pathways. By linking the HMG-CoA reductase pathway (which produces mevalonate) to the mevalonate pathway, these building block can be synthesized enzymatically from acetate, ATP, NAD(P)H and CoA. Here, the enzymes in these pathways are used to produce pathway intermediates and end-products in single-pot reactions and in remarkably high yield, ∼ 85%. A strategy for the regio-specific incorporation of isotopes into isoprenoid backbones is developed and used to synthesize a series of isotopomers of diphosphomevalonate, the immediate end-product of the mevalonate pathway. The enzymatic system is shown to be robust and capable of producing quantities of product in aqueous solutions that meet or exceed the highest levels achieved using genetically engineered organisms in high-density fermentation.http://europepmc.org/articles/PMC4143292?pdf=render |
| spellingShingle | Sofia B Rodriguez Thomas S Leyh An enzymatic platform for the synthesis of isoprenoid precursors. PLoS ONE |
| title | An enzymatic platform for the synthesis of isoprenoid precursors. |
| title_full | An enzymatic platform for the synthesis of isoprenoid precursors. |
| title_fullStr | An enzymatic platform for the synthesis of isoprenoid precursors. |
| title_full_unstemmed | An enzymatic platform for the synthesis of isoprenoid precursors. |
| title_short | An enzymatic platform for the synthesis of isoprenoid precursors. |
| title_sort | enzymatic platform for the synthesis of isoprenoid precursors |
| url | http://europepmc.org/articles/PMC4143292?pdf=render |
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