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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Bibliographic Details
Published in:Beilstein journal of organic chemistry 2019-11, Vol.15 (1), p.2889-2906
Main Authors: Helfrich, Eric J N, Lin, Geng-Min, Voigt, Christopher A, Clardy, Jon
Format: Article
Language:English
Subjects:
Bacteria
bacterial sesquiterpenes and diterpenes
Biological activity
Biosynthesis
Cancer
Chemistry
cytochrome p450
Diversification
Engineering
Enzymes
Evolution
Hydrocarbons
Hypotheses
Malaria
Metabolites
Natural products
pathway engineering
Review
synthetic biology
terpene biosynthesis
terpene cyclase
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Summary: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.
ISSN:1860-5397
2195-951X
1860-5397
DOI:10.3762/bjoc.15.283