ArticleMicrobial cell factories2020
Metabolic engineering of Escherichia coli for efficient production of L-alanyl-L-glutamine.
Article in Microbial cell factories, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- Photosynthetic production of glutamine through metabolic analysis-based engineering ofMetabolic engineering communications · 2026Article
- Effect and mechanism of mixed fungi synergistically enhancing the leaching of elements from wollastonite.Applied and environmental microbiology · 2026Article
- Functional Dipeptide Production by Immobilized Enzyme on Yeast Cell Surface.Journal of microbiology and biotechnology · 2026Article
- Modular pathway engineering for enhanced production ofApplied and environmental microbiology · 2025Article
- Effects of Alanyl-Glutamine Dipeptide Supplementation on Growth Performance, Nutrient Digestibility, Digestive Enzyme Activity, Immunity, and Antioxidant Status in Growing Laying Hens.Animals : an open access journal from MDPI · 2024Article
- Cerium ions immobilized magnetic graphite nitride decorated with L-Alanyl-L-Glutamine as new chelator for enrichment of phosphopeptides.Mikrochimica acta · 2023Article
- Multiplex gene knockout raises Ala-Gln production by Escherichia coli expressing amino acid ester acyltransferase.Applied microbiology and biotechnology · 2023Article
- Alanyl-Glutamine Protects against Lipopolysaccharide-Induced Liver Injury in Mice via Alleviating Oxidative Stress, Inhibiting Inflammation, and Regulating Autophagy.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundL-Alanyl-L-glutamine (AQ) is a functional dipeptide with high water solubility, good thermal stability and high bioavailability. It is widely used in clinical treatment, post-operative rehabilitation, sports health care and other fields. AQ is mainly produced via chemical synthesis which is complicated, time-consuming, labor-intensive, and have a low yield accompanied with the generation of by-products. It is therefore highly desirable to develop an efficient biotechnological process for the industrial production of AQ.
resultsA metabolically engineered E. coli strain for AQ production was developed by over-expressing L-amino acid α-ligase (BacD) from Bacillus subtilis, and inactivating the peptidases PepA, PepB, PepD, and PepN, as well as the dipeptide transport system Dpp. In order to use the more readily available substrate glutamic acid, a module for glutamine synthesis from glutamic acid was constructed by introducing glutamine synthetase (GlnA). Additionally, we knocked out glsA-glsB to block the first step in glutamine metabolism, and glnE-glnB involved in the ATP-dependent addition of AMP/UMP to a subunit of glutamine synthetase, which resulted in increased glutamine supply. Then the glutamine synthesis module was combined with the AQ synthesis module to develop the engineered strain that uses glutamic acid and alanine for AQ production. The expression of BacD and GlnA was further balanced to improve AQ production. Using the final engineered strain p15/AQ10 as a whole-cell biocatalyst, 71.7 mM AQ was produced with a productivity of 3.98 mM/h and conversion rate of 71.7%.
conclusionA metabolically engineered strain for AQ production was successfully developed via inactivation of peptidases, screening of BacD, introduction of glutamine synthesis module, and balancing the glutamine and AQ synthesis modules to improve the yield of AQ. This work provides a microbial cell factory for efficient production of AQ with industrial potential.
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