| Title: | Connecting central carbon and aromatic amino acid metabolisms to improve de novo 2-phenylethanol production in Saccharomyces cerevisiae |
| Author(s): | Hassing EJ; de Groot PA; Marquenie VR; Pronk JT; Daran JG; |
| Address: | "Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ, Delft, the Netherlands. Electronic address: E.Hassing@tudelft.nl. Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ, Delft, the Netherlands. Electronic address: padgroot@gmail.com. Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ, Delft, the Netherlands. Electronic address: V.R.Marquenie@student.tudelft.nl. Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ, Delft, the Netherlands. Electronic address: J.T.Pronk@tudelft.nl. Department of Biotechnology, Delft University of Technology, Van der Maasweg 9, 2629 HZ, Delft, the Netherlands. Electronic address: J.G.Daran@tudelft.nl" |
| DOI: | 10.1016/j.ymben.2019.09.011 |
| ISSN/ISBN: | 1096-7184 (Electronic) 1096-7176 (Linking) |
| Abstract: | "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 or de novo biosynthesis from sugar offer sustainable, reliable and natural production processes compared to chemical synthesis. Despite the ability of Saccharomyces cerevisiae to naturally synthesize 2PE, de novo synthesis 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 of p-hydroxy-phenylethanol without creating tyrosine auxotrophy significantly contributed to improve 2PE production in S. 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?ª+at a yield of 0.113?ª+mol?ª+mol(-1), which represents the highest yield for de novo produced 2PE in S. cerevisiae and other yeast species" |
| Keywords: | "*Amino Acids, Aromatic/genetics/metabolism Carbon/*metabolism *Metabolic Engineering Phenylethyl Alcohol/*metabolism *Saccharomyces cerevisiae/genetics/metabolism Saccharomyces cerevisiae Proteins/genetics/metabolism 2-Phenylethanol Aromatic amino acid pa;" |
| Notes: | "MedlineHassing, Else-Jasmijn de Groot, Philip A Marquenie, Vita R Pronk, Jack T Daran, Jean-Marc G eng Research Support, Non-U.S. Gov't Belgium 2019/10/02 Metab Eng. 2019 Dec; 56:165-180. doi: 10.1016/j.ymben.2019.09.011. Epub 2019 Sep 28" |
