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Multiple Metabolic Engineering Strategies to Improve Shikimate Titer in Escherichia coli.
| Content Provider | Europe PMC |
|---|---|
| Author | Bo, Taidong Wu, Chen Wang, Zeting Jiang, Hao Wang, Feiao Chen, Ning Li, Yanjun |
| Editor | Skonieczna-Żydecka, Karolina |
| Copyright Year | 2023 |
| Abstract | Shikimate is a valuable chiral precursor for synthesizing oseltamivir (Tamiflu®) and other chemicals. High production of shikimate via microbial fermentation has attracted increasing attention to overcome the unstable and expensive supply of shikimate extracted from plant resources. The current cost of microbial production of shikimate via engineered strains is still unsatisfactory, and thus more metabolic strategies need to be investigated to further increase the production efficiency. In this study, we first constructed a shikimate E. coli producer through the application of the non-phosphoenolpyruvate: carbohydrate phosphotransferase system (non-PTS) glucose uptake pathway, the attenuation of the shikimate degradation metabolism, and the introduction of a mutant of feedback-resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase. Inspired by the natural presence of bifunctional 3-dehydroquinate dehydratase (DHD)-shikimate dehydrogenase (SDH) enzyme in plants, we then designed an artificial fusion protein of DHD-SDH to decrease the accumulation of the byproduct 3-dehydroshikimate (DHS). Subsequently, a repressed shikimate kinase (SK) mutant was selected to promote shikimate accumulation without the supplementation of expensive aromatic substances. Furthermore, EsaR-based quorum sensing (QS) circuits were employed to regulate the metabolic flux distribution between cell growth and product synthesis. The final engineered strain dSA10 produced 60.31 g/L shikimate with a yield of 0.30 g/g glucose in a 5 L bioreactor. |
| Volume Number | 13 |
| PubMed Central reference number | PMC10305709 |
| Issue Number | 6 |
| PubMed reference number | 37367905 |
| Journal | Metabolites |
| e-ISSN | 22181989 |
| DOI | 10.3390/metabo13060747 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2023-06-12 |
| Access Restriction | Open |
| Rights License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors. |
| Subject Keyword | Escherichia coli metabolic engineering shikimate fusion protein shikimate kinase quorum sensing |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Endocrinology, Diabetes and Metabolism Molecular Biology |
