Orthogonal monoterpenoid biosynthesis in yeast constructed on an isomeric substrate
| Autor: | Sotirios C. Kampranis, Codruta Ignea, Antonios M. Makris, Mohammed Saddik Motawia, Claudia E. Vickers, Morten H. Raadam |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Science Saccharomyces cerevisiae General Physics and Astronomy 02 engineering and technology General Biochemistry Genetics and Molecular Biology Article Substrate Specificity Metabolic engineering 03 medical and health sciences chemistry.chemical_compound Synthetic biology Biosynthesis Isomerism Polyisoprenyl Phosphates Intramolecular Lyases lcsh:Science Multidisciplinary biology Substrate (chemistry) General Chemistry 021001 nanoscience & nanotechnology biology.organism_classification Yeast Biosynthetic Pathways Metabolic pathway 030104 developmental biology chemistry Biochemistry Metabolic Engineering Metabolic pathways Monoterpenes Mutagenesis Site-Directed Synthetic Biology lcsh:Q 0210 nano-technology Flux (metabolism) |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Ignea, C, Raadam, M H, Motawia, M S, Makris, A M, Vickers, C E & Kampranis, S C 2019, ' Orthogonal monoterpenoid biosynthesis in yeast constructed on an isomeric substrate ', Nature Communications, vol. 10 . https://doi.org/10.1038/s41467-019-11290-x Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Synthetic biology efforts for the production of valuable chemicals are frequently hindered by the structure and regulation of the native metabolic pathways of the chassis. This is particularly evident in the case of monoterpenoid production in Saccharomyces cerevisiae, where the canonical terpene precursor geranyl diphosphate is tightly coupled to the biosynthesis of isoprenoid compounds essential for yeast viability. Here, we establish a synthetic orthogonal monoterpenoid pathway based on an alternative precursor, neryl diphosphate. We identify structural determinants of isomeric substrate selectivity in monoterpene synthases and engineer five different enzymes to accept the alternative substrate with improved efficiency and specificity. We combine the engineered enzymes with dynamic regulation of metabolic flux to harness the potential of the orthogonal substrate and improve the production of industrially-relevant monoterpenes by several-fold compared to the canonical pathway. This approach highlights the introduction of synthetic metabolism as an effective strategy for high-value compound production. Titers of monoterpenoids production in yeast are low due to the fact that the geranyl diphosphate (GPP)-based pathway can redirect metabolic fluxes to growth. Here, the authors build an orthogonal pathway by selecting the cis isomer of GPP as an alternative precursor and achieve high titer monoterpene production. |
| Databáze: | OpenAIRE |
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