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Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization
Enzyme spatial organization is an evolved mechanism for facilitating multi‐step biocatalysis and can play an important role in the regulation of promiscuous enzymes. The latter function suggests that artificial spatial organization can be an untapped avenue for controlling the specificity of bioengi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646250/ https://www.ncbi.nlm.nih.gov/pubmed/37750486 http://dx.doi.org/10.1002/advs.202303415 |
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author | Cheah, Li Chen Liu, Lian Plan, Manuel R. Peng, Bingyin Lu, Zeyu Schenk, Gerhard Vickers, Claudia E. Sainsbury, Frank |
author_facet | Cheah, Li Chen Liu, Lian Plan, Manuel R. Peng, Bingyin Lu, Zeyu Schenk, Gerhard Vickers, Claudia E. Sainsbury, Frank |
author_sort | Cheah, Li Chen |
collection | PubMed |
description | Enzyme spatial organization is an evolved mechanism for facilitating multi‐step biocatalysis and can play an important role in the regulation of promiscuous enzymes. The latter function suggests that artificial spatial organization can be an untapped avenue for controlling the specificity of bioengineered metabolic pathways. A promiscuous terpene synthase (nerolidol synthase) is co‐localized and spatially organized with the preceding enzyme (farnesyl diphosphate synthase) in a heterologous production pathway, via translational protein fusion and/or co‐encapsulation in a self‐assembling protein cage. Spatial organization enhances nerolidol production by ≈11‐ to ≈62‐fold relative to unorganized enzymes. More interestingly, striking differences in the ratio of end products (nerolidol and linalool) are observed with each spatial organization approach. This demonstrates that artificial spatial organization approaches can be harnessed to modulate the product profiles of promiscuous enzymes in engineered pathways in vivo. This extends the application of spatial organization beyond situations where multiple enzymes compete for a single substrate to cases where there is competition among multiple substrates for a single enzyme. |
format | Online Article Text |
id | pubmed-10646250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106462502023-09-26 Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization Cheah, Li Chen Liu, Lian Plan, Manuel R. Peng, Bingyin Lu, Zeyu Schenk, Gerhard Vickers, Claudia E. Sainsbury, Frank Adv Sci (Weinh) Research Articles Enzyme spatial organization is an evolved mechanism for facilitating multi‐step biocatalysis and can play an important role in the regulation of promiscuous enzymes. The latter function suggests that artificial spatial organization can be an untapped avenue for controlling the specificity of bioengineered metabolic pathways. A promiscuous terpene synthase (nerolidol synthase) is co‐localized and spatially organized with the preceding enzyme (farnesyl diphosphate synthase) in a heterologous production pathway, via translational protein fusion and/or co‐encapsulation in a self‐assembling protein cage. Spatial organization enhances nerolidol production by ≈11‐ to ≈62‐fold relative to unorganized enzymes. More interestingly, striking differences in the ratio of end products (nerolidol and linalool) are observed with each spatial organization approach. This demonstrates that artificial spatial organization approaches can be harnessed to modulate the product profiles of promiscuous enzymes in engineered pathways in vivo. This extends the application of spatial organization beyond situations where multiple enzymes compete for a single substrate to cases where there is competition among multiple substrates for a single enzyme. John Wiley and Sons Inc. 2023-09-26 /pmc/articles/PMC10646250/ /pubmed/37750486 http://dx.doi.org/10.1002/advs.202303415 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Cheah, Li Chen Liu, Lian Plan, Manuel R. Peng, Bingyin Lu, Zeyu Schenk, Gerhard Vickers, Claudia E. Sainsbury, Frank Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization |
title | Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization |
title_full | Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization |
title_fullStr | Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization |
title_full_unstemmed | Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization |
title_short | Product Profiles of Promiscuous Enzymes Can be Altered by Controlling In Vivo Spatial Organization |
title_sort | product profiles of promiscuous enzymes can be altered by controlling in vivo spatial organization |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646250/ https://www.ncbi.nlm.nih.gov/pubmed/37750486 http://dx.doi.org/10.1002/advs.202303415 |
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