ArticleMicrobial cell factories2016
Production of para-aminobenzoic acid from different carbon-sources in engineered Saccharomyces cerevisiae.
Article in Microbial cell factories, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 37 citations in OpenAlex.
- Combinatorial engineering pinpoints shikimate pathway bottlenecks in para-aminobenzoic acid production in Pseudomonas putida.Journal of biological engineering · 2025Article
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- Understanding coenzyme Q.Physiological reviews · 2024Review
- De novo biosynthesis of 2-hydroxyterephthalic acid, the monomer for high-performance hydroxyl modified PBO fiber, by enzymatic Kolbe-Schmitt reaction with COBiotechnology for biofuels and bioproducts · 2023Article
- Microbial applications for sustainable space exploration beyond low Earth orbit.NPJ microgravity · 2023Review
- A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin.Nature communications · 2022Article
- Vitamin requirements and biosynthesis in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2020Review
- Metabolic engineering and transcriptomic analysis of Saccharomyces cerevisiae producing p-coumaric acid from xylose.Microbial cell factories · 2019Article
- Metabolic engineering of Bacillus subtilis for production of para-aminobenzoic acid - unexpected importance of carbon source is an advantage for space application.Microbial biotechnology · 2019Article
- Metabolic engineering of microorganisms for production of aromatic compounds.Microbial cell factories · 2019Review
- Metabolic Engineering of the Shikimate Pathway for Production of Aromatics and Derived Compounds-Present and Future Strain Construction Strategies.Frontiers in bioengineering and biotechnology · 2018Article
- Metabolic Engineering ofFrontiers in bioengineering and biotechnology · 2016Article
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3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundBiological production of the aromatic compound para-aminobenzoic acid (pABA) is of great interest to the chemical industry. Besides its application in pharmacy and as crosslinking agent for resins and dyes pABA is a potential precursor for the high-volume aromatic feedstocks terephthalic acid and para-phenylenediamine. The yeast Saccharomyces cerevisiae synthesises pABA in the shikimate pathway: Outgoing from the central shikimate pathway intermediate chorismate, pABA is formed in two enzyme-catalysed steps, encoded by the genes ABZ1 and ABZ2. In this study S. cerevisiae metabolism was genetically engineered for the overproduction of pABA. Using in silico metabolic modelling an observed impact of carbon-source on product yield was investigated and exploited to optimize production.
resultsA strain that incorporated the feedback resistant ARO4 (K229L) and deletions in the ARO7 and TRP3 genes, in order to channel flux to chorismate, was used to screen different ABZ1 and ABZ2 genes for pABA production. In glucose based shake-flaks fermentations the highest titer (600 µM) was reached when over-expressing the ABZ1 and ABZ2 genes from the wine yeast strains AWRI1631 and QA23, respectively. In silico metabolic modelling indicated a metabolic advantage for pABA production on glycerol and combined glycerol-ethanol carbon-sources. This was confirmed experimentally, the empirical ideal glycerol to ethanol uptake ratios of 1:2-2:1 correlated with the model. A (13)C tracer experiment determined that up to 32% of the produced pABA originated from glycerol. Finally, in fed-batch bioreactor experiments pABA titers of 1.57 mM (215 mg/L) and carbon yields of 2.64% could be achieved.
conclusionIn this study a combination of genetic engineering and in silico modelling has proven to be a complete and advantageous approach to increase pABA production. Especially the enzymes that catalyse the last two steps towards product formation appeared to be crucial to direct flux to pABA. A stoichiometric model for carbon-utilization proved useful to design carbon-source composition, leading to increased pABA production. The reported pABA concentrations and yields are, to date, the highest in S. cerevisiae and the second highest in a microbial production system, underlining the great potential of yeast as a cell factory for renewable aromatic feedstocks.
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