Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering

Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our kn...

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Main Authors: Lin, Geng-Min, Voigt, Christopher A.
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: Beilstein Institut 2020
Online Access:https://hdl.handle.net/1721.1/125290
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author Lin, Geng-Min
Voigt, Christopher A.
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Lin, Geng-Min
Voigt, Christopher A.
author_sort Lin, Geng-Min
collection MIT
description Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our knowledge of how they are biosynthesized is limited, particularly when compared to the well-studied thiotemplate assembly lines. Bacteria have only recently been recognized as having the genetic potential to biosynthesize a large number of complex terpenoids, but our current ability to associate genetic potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This functional promiscuity of terpene biosynthetic pathways renders terpene biosynthesis susceptible to rational pathway engineering using the latest developments in the field of synthetic biology. These engineered pathways will not only facilitate the rational creation of both known and novel terpenoids, their development will deepen our understanding of a significant branch of biosynthesis. The biosynthetic insights gained will likely empower a greater degree of engineering proficiency for non-natural terpene biosynthetic pathways and pave the way towards the biotechnological production of high value terpenoids.
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spelling mit-1721.1/1252902022-10-02T03:39:50Z Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering Lin, Geng-Min Voigt, Christopher A. Massachusetts Institute of Technology. Department of Biological Engineering Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our knowledge of how they are biosynthesized is limited, particularly when compared to the well-studied thiotemplate assembly lines. Bacteria have only recently been recognized as having the genetic potential to biosynthesize a large number of complex terpenoids, but our current ability to associate genetic potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This functional promiscuity of terpene biosynthetic pathways renders terpene biosynthesis susceptible to rational pathway engineering using the latest developments in the field of synthetic biology. These engineered pathways will not only facilitate the rational creation of both known and novel terpenoids, their development will deepen our understanding of a significant branch of biosynthesis. The biosynthetic insights gained will likely empower a greater degree of engineering proficiency for non-natural terpene biosynthetic pathways and pave the way towards the biotechnological production of high value terpenoids. 2020-05-18T19:00:14Z 2020-05-18T19:00:14Z 2019-11 2020-03-18T14:21:07Z Article http://purl.org/eprint/type/JournalArticle 1860-5397 https://hdl.handle.net/1721.1/125290 Helfrich, Eric J. N. et al. “Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering.” Beilstein Journal of Organic Chemistry 15 (2019): 2889-2906 © 2019 The Author(s) en 10.3762/bjoc.15.283 Beilstein Journal of Organic Chemistry Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Beilstein Institut Beilstein
spellingShingle Lin, Geng-Min
Voigt, Christopher A.
Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering
title Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering
title_full Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering
title_fullStr Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering
title_full_unstemmed Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering
title_short Bacterial terpene biosynthesis: Challenges and opportunities for pathway engineering
title_sort bacterial terpene biosynthesis challenges and opportunities for pathway engineering
url https://hdl.handle.net/1721.1/125290
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AT voigtchristophera bacterialterpenebiosynthesischallengesandopportunitiesforpathwayengineering