ArticleBiotechnology for biofuels2019
Modular systems metabolic engineering enables balancing of relevant pathways for l-histidine production with
Article in Biotechnology for biofuels, 2019. 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, 35 citations in OpenAlex.
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- A manually curated compendium of expression profiles for the microbial cell factory Corynebacterium glutamicum.Scientific data · 2022Article
- O-Acetyl-L-homoserine production enhanced by pathway strengthening and acetate supplementation in Corynebacterium glutamicum.Biotechnology for biofuels and bioproducts · 2022Article
- Biosensor-based isolation of amino acid-producingMetabolic engineering communications · 2021Article
- Exploring the Potential ofFrontiers in bioengineering and biotechnology · 2021Article
- A Timed Off-Switch for Dynamic Control of Gene Expression inFrontiers in bioengineering and biotechnology · 2021Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundl-Histidine biosynthesis is embedded in an intertwined metabolic network which renders microbial overproduction of this amino acid challenging. This is reflected in the few available examples of histidine producers in literature. Since knowledge about the metabolic interplay is limited, we systematically perturbed the metabolism of
resultsThe engineered strains produced l-histidine, equimolar amounts of glycine, and possessed heavily decreased intracellular adenylate concentrations, despite a stable adenylate energy charge. FBA identified regeneration of ATP from 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) as crucial step for l-histidine production and SMP identified strong intracellular accumulation of inosine monophosphate (IMP) in the engineered strains. Energy engineering readjusted the intracellular IMP and ATP levels to wild-type niveau and reinforced the intrinsic low ATP regeneration capacity to maintain a balanced energy state of the cell. SMP further indicated limitations in the C
conclusionBy applying the modularized metabolic engineering approach combined with SMP and FBA, we identified an intrinsically low ATP regeneration capacity, which prevents to maintain a balanced energy state of the cell in an l-histidine overproduction scenario and an insufficient supply of C
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