Overproduction of Phenolic Compounds in <i>Pseudomonas putida</i> KT2440 Through Endogen Deregulation of the Shikimate Pathway
Metabolic engineering of the shikimate pathway offers a promising strategy for enhancing the production of aromatic compounds in microbial hosts. However, feedback inhibition of key enzymes, such as the 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP synthase), often limits the yield of t...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | BioChem |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-6411/5/1/4 |
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| Summary: | Metabolic engineering of the shikimate pathway offers a promising strategy for enhancing the production of aromatic compounds in microbial hosts. However, feedback inhibition of key enzymes, such as the 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHP synthase), often limits the yield of target products. In this study, we focused on the DAHP synthase (AroF-I) from <i>Pseudomonas putida</i>. Through computational modeling and experimental validation, we identified specific amino-acid residues responsible for tyrosine-mediated feedback inhibition. By targeted mutagenesis, we engineered DAHP synthase variants that exhibit reduced sensitivity to feedback inhibition. The introduction of these engineered enzymes into a metabolically engineered <i>Pseudomonas putida</i> strain resulted in significantly increased production of p-coumaric acid. Our findings provide valuable insights into the regulation of the shikimate pathway and demonstrate the potential of protein engineering to improve microbial production of aromatic compounds. |
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| ISSN: | 2673-6411 |