Connecting central carbon and aromatic amino acid metabolisms to improve de novo 2-phenylethanol production in Saccharomyces cerevisiae
| Autor: | Philip A. de Groot, Jack T. Pronk, Else Jasmijn Hassing, Jean-Marc Daran, Vita R. Marquenie |
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| Rok vydání: | 2019 |
| Předmět: |
0106 biological sciences
Saccharomyces cerevisiae Proteins Auxotrophy Saccharomyces cerevisiae Bioengineering Pentose phosphate pathway 01 natural sciences Applied Microbiology and Biotechnology Metabolic engineering Amino Acids Aromatic 03 medical and health sciences chemistry.chemical_compound de novo biosynthesis 010608 biotechnology Aromatic amino acids Pyruvate kinase 030304 developmental biology 2. Zero hunger 0303 health sciences biology Phenylethyl Alcohol biology.organism_classification Carbon Yeast De novo synthesis Metabolic Engineering Biochemistry chemistry Prephenate dehydrogenase downregulation Aromatic amino acid pathway engineering 2-Phenylethanol Phosphoenolpyruvate carboxykinase Biotechnology |
| Zdroj: | Metabolic Engineering Metabolic Engineering, 56 |
| ISSN: | 1096-7176 |
| Popis: | The organic compound 2-phenylethanol (2PE) has a pleasant floral scent and is intensively used in the cosmetic and food industries. Microbial production of 2PE by phenylalanine bioconversion orde novobiosynthesis from sugar offer sustainable, reliable and natural production processes compared to chemical synthesis. Despite the ability ofSaccharomyces cerevisiaeto naturally synthesize 2PE,de novosynthesis in high concentration and yield remains a metabolic engineering challenge. Here, we demonstrate that improving phosphoenolpyruvate supply by expressing pyruvate kinase variants and eliminating the formation ofp-hydroxy-phenylethanol without creating tyrosine auxotrophy significantly contributed to improve 2PE production inS. cerevisiae. In combination with the engineering of the aromatic amino acid biosynthesis and Ehrlich pathway, these mutations enabled better connection between glycolysis and pentose phosphate pathway optimizing carbon flux towards 2PE. However, attempts to further connect these two parts of central carbon metabolism by redirecting fructose-6P towards erythrose-4P by expressing a phosphoketolase-phosphotransacetylase pathway did not result in improved performance. The best performing strains were capable of producing 13mM of 2PE at a yield of 0.113 mol mol-1, which represents the highest yield forde novoproduced 2PE inS. cerevisiaeand other yeast species. |
| Databáze: | OpenAIRE |
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