Metabolic enzyme clustering by coiled coils improves the biosynthesis of resveratrol and mevalonate

Metabolic enzyme clustering by coiled coils improves the biosynthesis of resveratrol and mevalonate

The clustering of biosynthetic enzymes is used in nature to channel reaction products and increase the yield of compounds produced by multiple reaction steps. The coupling of multiple enzymes has been shown to increase the biosynthetic product yield. Different clustering strategies have particular a...

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Bibliographic Details
Published in:AMB Express Vol. 10; no. 1; p. 97
Main Authors: Fink, Tina, Stevović, Bojana, Verwaal, René, Roubos, Johannes A., Gaber, Rok, Benčina, Mojca, Jerala, Roman, Gradišar, Helena
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 24-05-2020
Springer Nature B.V
SpringerOpen
Subjects:
Biomedical and Life Sciences
Biosynthesis
Biotechnology
Clustering
Coils
Coupling (molecular)
Designed coiled-coil dimers
Dimers
Domains
E coli
Enzyme clustering
Enzymes
Life Sciences
Mevalonate
Mevalonic acid
Microbial Genetics and Genomics
Microbiology
Original
Original Article
Reaction products
Resveratrol
Stability
Biosynthesis
Mevalonate
Enzyme clustering
Designed coiled-coil dimers
Resveratrol
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Summary:The clustering of biosynthetic enzymes is used in nature to channel reaction products and increase the yield of compounds produced by multiple reaction steps. The coupling of multiple enzymes has been shown to increase the biosynthetic product yield. Different clustering strategies have particular advantages as the spatial organization of multiple enzymes creates biocatalytic cascades with a higher efficiency of biochemical reaction. However, there are also some drawbacks, such as misfolding and the variable stability of interaction domains, which may differ between particular biosynthetic reactions and the host organism. Here, we compared different protein-based clustering strategies, including direct fusion, fusion mediated by intein, and noncovalent interactions mediated through small coiled-coil dimer-forming domains. The clustering of enzymes through orthogonally designed coiled-coil interaction domains increased the production of resveratrol in Escherichia coli more than the intein-mediated fusion of biosynthetic enzymes. The improvement of resveratrol production correlated with the stability of the coiled-coil dimers. The coiled-coil fusion-based approach also increased mevalonate production in Saccharomyces cerevisiae , thus demonstrating the wider applicability of this strategy.
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ISSN:2191-0855
2191-0855
DOI:10.1186/s13568-020-01031-5