Protein engineering strategies for microbial production of isoprenoids

© 2020 The Authors Isoprenoids comprise one of the most chemically diverse family of natural products with high commercial interest. The structural diversity of isoprenoids is mainly due to the modular activity of three distinct classes of enzymes, including prenyl diphosphate synthases, terpene syn...

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Main Authors: Daletos, Georgios, Stephanopoulos, Gregory
Other Authors: Massachusetts Institute of Technology. Department of Chemical Engineering
Format: Article
Language:English
Published: Elsevier BV 2021
Online Access:https://hdl.handle.net/1721.1/135314
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author Daletos, Georgios
Stephanopoulos, Gregory
author2 Massachusetts Institute of Technology. Department of Chemical Engineering
author_facet Massachusetts Institute of Technology. Department of Chemical Engineering
Daletos, Georgios
Stephanopoulos, Gregory
author_sort Daletos, Georgios
collection MIT
description © 2020 The Authors Isoprenoids comprise one of the most chemically diverse family of natural products with high commercial interest. The structural diversity of isoprenoids is mainly due to the modular activity of three distinct classes of enzymes, including prenyl diphosphate synthases, terpene synthases, and cytochrome P450s. The heterologous expression of these enzymes in microbial systems is suggested to be a promising sustainable way for the production of isoprenoids. Several limitations are associated with native enzymes, such as low stability, activity, and expression profiles. To address these challenges, protein engineering has been applied to improve the catalytic activity, selectivity, and substrate turnover of enzymes. In addition, the natural promiscuity and modular fashion of isoprenoid enzymes render them excellent targets for combinatorial studies and the production of new-to-nature metabolites. In this review, we discuss key individual and multienzyme level strategies for the successful implementation of enzyme engineering towards efficient microbial production of high-value isoprenoids. Challenges and future directions of protein engineering as a complementary strategy to metabolic engineering are likewise outlined.
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spelling mit-1721.1/1353142023-09-12T19:48:16Z Protein engineering strategies for microbial production of isoprenoids Daletos, Georgios Stephanopoulos, Gregory Massachusetts Institute of Technology. Department of Chemical Engineering © 2020 The Authors Isoprenoids comprise one of the most chemically diverse family of natural products with high commercial interest. The structural diversity of isoprenoids is mainly due to the modular activity of three distinct classes of enzymes, including prenyl diphosphate synthases, terpene synthases, and cytochrome P450s. The heterologous expression of these enzymes in microbial systems is suggested to be a promising sustainable way for the production of isoprenoids. Several limitations are associated with native enzymes, such as low stability, activity, and expression profiles. To address these challenges, protein engineering has been applied to improve the catalytic activity, selectivity, and substrate turnover of enzymes. In addition, the natural promiscuity and modular fashion of isoprenoid enzymes render them excellent targets for combinatorial studies and the production of new-to-nature metabolites. In this review, we discuss key individual and multienzyme level strategies for the successful implementation of enzyme engineering towards efficient microbial production of high-value isoprenoids. Challenges and future directions of protein engineering as a complementary strategy to metabolic engineering are likewise outlined. 2021-10-27T20:22:56Z 2021-10-27T20:22:56Z 2020 2021-06-22T16:42:58Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135314 en 10.1016/J.MEC.2020.E00129 Metabolic Engineering Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier
spellingShingle Daletos, Georgios
Stephanopoulos, Gregory
Protein engineering strategies for microbial production of isoprenoids
title Protein engineering strategies for microbial production of isoprenoids
title_full Protein engineering strategies for microbial production of isoprenoids
title_fullStr Protein engineering strategies for microbial production of isoprenoids
title_full_unstemmed Protein engineering strategies for microbial production of isoprenoids
title_short Protein engineering strategies for microbial production of isoprenoids
title_sort protein engineering strategies for microbial production of isoprenoids
url https://hdl.handle.net/1721.1/135314
work_keys_str_mv AT daletosgeorgios proteinengineeringstrategiesformicrobialproductionofisoprenoids
AT stephanopoulosgregory proteinengineeringstrategiesformicrobialproductionofisoprenoids