ArticleMicrobial cell factories2019
Metabolic engineering of Escherichia coli BL21 (DE3) for de novo production of L-DOPA from D-glucose.
Article in Microbial cell factories, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 108 citations in OpenAlex.
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- Comparative analysis of precursor supply and pathway reinforcement strategies for shikimic acid biosynthesis in Pseudomonas putida.Microbial cell factories · 2026Article
- Recent advances in nonprotein amino acids: insights from function to biosynthesis.Journal of animal science and biotechnology · 2026Review
- Efficient synthesis of l-DOPA inSynthetic and systems biotechnology · 2026Article
- Engineering non-P450 3-hydroxylase forSynthetic and systems biotechnology · 2025Article
- Directed evolution of L-DOPA sensing and production enables efficient incorporation of an expanded genetic code into proteins.bioRxiv : the preprint server for biology · 2025Article
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- Efficient production of hydroxysalidroside inSynthetic and systems biotechnology · 2025Article
- The knowledge driven DBTL cycle provides mechanistic insights while optimising dopamine production in Escherichia coli.Microbial cell factories · 2025Article
- Development of the autonomous lab system to support biotechnology research.Scientific reports · 2025Article
- Investigation of Eumelanin Biosynthesis inMicroorganisms · 2025Article
- Production of aromatic amino acids and their derivatives by Escherichia coli and Corynebacterium glutamicum.World journal of microbiology & biotechnology · 2025Review
- Microbial engineering for monocyclic aromatic compounds production.FEMS microbiology reviews · 2025Review
- Expanding the application of tyrosine: engineering microbes for the production of tyrosine and its derivatives.Frontiers in bioengineering and biotechnology · 2025Review
- Computer-aided design and implementation of efficient biosynthetic pathways to produce high added-value products derived from tyrosine inFrontiers in bioengineering and biotechnology · 2024Article
- Advances in 4-Hydroxyphenylacetate-3-hydroxylase Monooxygenase.Molecules (Basel, Switzerland) · 2023Review
- Metabolic Engineering of De Novo Pathway for the Production of 2'-Fucosyllactose in Escherichia coli.Molecular biotechnology · 2023Article
- Divergent directed evolution of a TetR-type repressor towards aromatic molecules.Nucleic acids research · 2023Article
- Enhancement of phycocyanobilin biosynthesis inSynthetic and systems biotechnology · 2023Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProduction of L-tyrosine is gaining grounds as the market size of 3,4-dihydroxyphenyl-L-alanine (L-DOPA) is expected to increase due to increasing cases of Parkinson's disease a neurodegenerative disease. Attempts to overproduce L-tyrosine for conversion to L-DOPA has stemmed on the overexpressing of critical pathway enzymes, an introduction of feedback-resistant enzymes, and deregulation of transcriptional regulators.
resultsAn E. coli BL21 (DE3) was engineered by deleting tyrR, ptsG, crr, pheA and pykF while directing carbon flow through the overexpressing of galP and glk. TktA and PpsA were also overexpressed to enhance the accumulation of E4P and PEP. Directed evolution was then applied on HpaB to optimize its activity. Three mutants, G883R, G883A, L1231M, were identified to have improved activity as compared to the wild-type hpaB showing a 3.03-, 2.9- and 2.56-fold increase in L-DOPA production respectively. The use of strain LP-8 resulted in the production of 691.24 mg/L and 25.53 g/L of L-DOPA in shake flask and 5 L bioreactor, respectively.
conclusionDeletion of key enzymes to channel flux towards the shikimate pathway coupled with the overexpression of pathway enzymes enhanced the availability of L-tyrosine for L-DOPA production. Enhancing the activity of HpaB increased L-DOPA production from glucose and glycerol. This work demonstrates that increasing the availability of L-tyrosine and enhancing enzyme activity ensures maximum L-DOPA productivity.
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