Rational Design of Flavonoid Production Routes Using Combinatorial and Precursor-Directed Biosynthesis
| Autor: | Vito Valiante, Sandra Hoefgen, Daniel F.O. Braga, Miriam A. Rosenbaum, Johann E Kufs, Julia Rautschek, Julian Thiele, Alexander U Bissell, Lars Regestein, Jonas Fiedler, Carola Graf |
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| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Chalcone synthase Flavonoid Genetic Vectors Biomedical Engineering Arabidopsis Computational biology 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Enzyme catalysis Substrate Specificity 03 medical and health sciences Multigene expression Polyketide chemistry.chemical_compound Chalcones Biosynthesis Flavonoid derivatives 010608 biotechnology Escherichia coli 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Chemistry Arabidopsis Proteins fungi Rational design food and beverages General Medicine Malonyl Coenzyme A Polyketides Flavanones biology.protein Synthetic Biology Polyketide Synthases Acyltransferases Plasmids |
| Zdroj: | ACS synthetic biology. 9(7) |
| ISSN: | 2161-5063 |
| Popis: | Combinatorial biosynthesis has great potential for designing synthetic circuits and amplifying the production of new active compounds. Studies on multienzyme cascades are extremely useful for improving our knowledge on enzymatic catalysis. In particular, the elucidation of enzyme substrate promiscuity can be potentially used for bioretrosynthetic approaches, leading to the design of alternative and more convenient routes to produce relevant molecules. In this perspective, plant-derived polyketides are extremely adaptable to those synthetic biological applications. Here, we present a combination of an in vitro CoA ligase activity assay coupled with a bacterial multigene expression system that leads to precursor-directed biosynthesis of 21 flavonoid derivatives. When the vast knowledge from protein databases is exploited, the herein presented procedure can be easily repeated with additional plant-derived polyketides. Lastly, we report an efficient in vivo expression system that can be further exploited to heterologously express pathways not necessarily related to plant polyketide synthases. |
| Databáze: | OpenAIRE |
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