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Orthogonal monoterpenoid biosynthesis in yeast constructed on an isomeric substrate.
- Source :
-
Nature communications [Nat Commun] 2019 Aug 23; Vol. 10 (1), pp. 3799. Date of Electronic Publication: 2019 Aug 23. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Biosynthetic Pathways genetics
Intramolecular Lyases metabolism
Isomerism
Mutagenesis, Site-Directed
Polyisoprenyl Phosphates metabolism
Saccharomyces cerevisiae enzymology
Saccharomyces cerevisiae Proteins metabolism
Substrate Specificity genetics
Synthetic Biology
Intramolecular Lyases genetics
Metabolic Engineering
Monoterpenes metabolism
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31444322
- Full Text :
- https://doi.org/10.1038/s41467-019-11290-x