scholarly journals Enhanced production of γ-amino acid 3-amino-4-hydroxybenzoic acid by recombinant Corynebacterium glutamicum under oxygen limitation

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hideo Kawaguchi ◽  
Tomohisa Hasunuma ◽  
Yasuo Ohnishi ◽  
Takashi Sazuka ◽  
Akihiko Kondo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Corynebacterium Glutamicum ◽  
Aromatic Compounds ◽  
Metabolic Pathways ◽  
Oxygen Limitation ◽  
Specific Productivity ◽  
Hydroxybenzoic Acid ◽  
Metabolome Analysis ◽  
Aerobic Conditions

Abstract Background Bio-based aromatic compounds are of great interest to the industry, as commercial production of aromatic compounds depends exclusively on the unsustainable use of fossil resources or extraction from plant resources. γ-amino acid 3-amino-4-hydroxybenzoic acid (3,4-AHBA) serves as a precursor for thermostable bioplastics. Results Under aerobic conditions, a recombinant Corynebacterium glutamicum strain KT01 expressing griH and griI genes derived from Streptomyces griseus produced 3,4-AHBA with large amounts of amino acids as by-products. The specific productivity of 3,4-AHBA increased with decreasing levels of dissolved oxygen (DO) and was eightfold higher under oxygen limitation (DO = 0 ppm) than under aerobic conditions (DO ≥ 2.6 ppm). Metabolic profiles during 3,4-AHBA production were compared at three different DO levels (0, 2.6, and 5.3 ppm) using the DO-stat method. Results of the metabolome analysis revealed metabolic shifts in both the central metabolic pathway and amino acid metabolism at a DO of < 33% saturated oxygen. Based on this metabolome analysis, metabolic pathways were rationally designed for oxygen limitation. An ldh deletion mutant, with the loss of lactate dehydrogenase, exhibited 3.7-fold higher specific productivity of 3,4-AHBA at DO = 0 ppm as compared to the parent strain KT01 and produced 5.6 g/L 3,4-AHBA in a glucose fed-batch culture. Conclusions Our results revealed changes in the metabolic state in response to DO concentration and provided insights into oxygen supply during fermentation and the rational design of metabolic pathways for improved production of related amino acids and their derivatives. Graphical Abstract

scholarly journals The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cancer Therapy ◽  
Metabolic Pathways ◽  
Essential Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Redox Status ◽  
Antioxidant Systems

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.

Amino Acids

2016 ◽  
Author(s):  
Daniel Rabier
Keyword(s):  
Amino Acids ◽  
Plasma Membrane ◽  
Amino Acid ◽  
Metabolic Pathways ◽  
Metabolic Diseases ◽  
Biological Fluids ◽  
Catabolic Pathway ◽  
Transport Pathways ◽  
Intermediate Metabolites ◽  
Protein Group

Amino acids present in the different biological fluids belong to two groups: the protein group, with the 21 classical amino acids constituting the backbone of the protein, and the nonprotein group, appearing in different metabolic pathways as intermediate metabolites. It is important to know and to be able to recognize the latter, as they are the markers of many inherited metabolic diseases. Three kinds of pathways must be considered: the catabolic pathways, the synthesis pathways, and the transport pathways. A disorder on a catabolic pathway induces an increase of all metabolites upstream and so an increase of the starting amino acid in all fluids. Any disorder on the synthetic pathway of a particular amino acid will induce a decrease of this amino acid in all fluids. When a transporter is located on a plasma membrane, its deficiency will result in normal or low concentration in plasma concomitant to a high excretion in urine.

scholarly journals Decoding the Complex Crossroad of Tryptophan Metabolic Pathways

2022 ◽  
Vol 23 (2) ◽  
pp. 787
Author(s):  
Giada Mondanelli ◽  
Claudia Volpi ◽  
Ciriana Orabona
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Metabolic Pathways ◽  
Aromatic Amino Acid ◽  
Living Cells ◽  
Cellular Homeostasis

Among the 20 amino acids needed for protein synthesis, Tryptophan (Trp) is an aromatic amino acid fundamental not only for the synthesis of the major components of living cells (namely, the proteins), but also for the maintenance of cellular homeostasis [...]

scholarly journals Single amino acid-promoted reactions link a non-enzymatic chemical network to the early evolution of enzymatic pentose phosphate pathway

2020 ◽  
Author(s):  
Gabriel Piedrafita ◽  
Sreejith Varma ◽  
Cecilia Castro ◽  
Christoph Messner ◽  
Lukasz Szyrwiel ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Pentose Phosphate Pathway ◽  
Metabolic Pathways ◽  
Metal Ion ◽  
Enzymatic Reaction ◽  
Pentose Phosphate ◽  
Early Evolution ◽  
Environmental Chemical ◽  
Rna Backbone

AbstractHow metabolic pathways emerged in early evolution remains largely unknown. Recently discovered chemical networks driven by iron and sulfur resemble reaction sequences found within glycolysis, gluconeogenesis, the oxidative and reductive Krebs cycle, the Wood Ljungdahl as well as the S-adenosylmethionine pathways, components of the core cellular metabolic network. These findings suggest that the evolution of central metabolism was primed by environmental chemical reactions, implying that non-enzymatic reaction networks served as a “template” in the evolution of enzymatic activities. We speculated that the turning point for this transition would depend on the catalytic properties of the simplest structural components of proteins, single amino acids. Here, we systematically combine constituents of Fe(II)-driven non-enzymatic reactions resembling glycolysis and pentose phosphate pathway (PPP), with single proteinogenic amino acids. Multiple reaction rates are enhanced by amino acids. In particular, cysteine is able to replace (and/or complement) the metal ion Fe(II) in driving the non-enzymatic formation of the RNA-backbone metabolite ribose 5-phosphate from 6-phosphogluconate, a rate-limiting reaction of the oxidative PPP. In the presence of both Fe(II) and cysteine, a complex is formed, enabling the non-enzymatic reaction to proceed at a wide range of temperatures. At mundane temperatures, this ‘minimal enzyme-like complex’ achieves a much higher specificity in the formation of ribose 5-phosphate than the Fe(II)-driven reaction at high temperatures. Hence, simple amino acids can accelerate key steps within metal-promoted metabolism-like chemical networks. Our results imply a stepwise scenario, in which environmental chemical networks served as primers in the early evolution of the metabolic network structure.Significance StatementThe evolutionary roots of metabolic pathways are barely understood. Here we show results consistent with a stepwise scenario during the evolution of (enzymatic) metabolism, starting from non-enzymatic chemical networks. By systematic screening of metabolic-like reactivities in vitro, and using high-throughput analytical techniques, we identify an iron/cysteine complex to act as a ‘minimal enzymelike complex’, which consists of a metal ion, an amino acid, and a sugar phosphate ligand. Integrated in a metal-driven, non-enzymatic pentose phosphate pathway, it promotes the formation of the RNA-backbone precursor ribose 5-phosphate at ambient temperature.

scholarly journals Characterization of Methionine Export in Corynebacterium glutamicum

2005 ◽  
Vol 187 (11) ◽  
pp. 3786-3794 ◽  
Author(s):  
Christian Trötschel ◽  
Dietrich Deutenberg ◽  
Brigitte Bathe ◽  
Andreas Burkovski ◽  
Reinhard Krämer
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Corynebacterium Glutamicum ◽  
High Capacity ◽  
Futile Cycle ◽  
Two Component ◽  
Methionine Concentration ◽  
Metabolic Conditions ◽  
Export System

ABSTRACT Corynebacterium glutamicum is known for its effective excretion of amino acids under particular metabolic conditions. Concomitant activities of uptake and excretion systems would create an energy-wasting futile cycle; amino acid export systems are therefore tightly regulated. We have used a DNA microarray approach to identify genes for membrane proteins which are overexpressed under conditions of elevated cytoplasmic concentrations of methionine. One of these genes was brnF, coding for the larger subunit of BrnFE, a previously identified two-component isoleucine export system. By deletion, complementation, and overexpression of the brnFE genes in a C. glutamicum strain, in which the two uptake systems for methionine were inactivated, we identified BrnFE as being responsible for methionine export. In the presence of both substrates in the cytoplasm, BrnFE was found to transport isoleucine and methionine at similar rates. The expression of the brnFE gene cluster depends on an Lrp-type transcription factor and was shown to be strongly induced by increasing cytoplasmic methionine concentration. Methionine was a better inducer than isoleucine, indicating that methionine rather than isoleucine might be the native substrate of BrnFE. When the synthesis of BrnFE was blocked by chloramphenicol, fast methionine export was still observed, but only at greatly increased cytoplasmic levels of this amino acid. This indicates the presence of at least one other methionine export system, presumably with low affinity but high capacity. Under conditions where cytoplasmic methionine does not exceed a concentration of 50 mM, BrnFE is the dominant export system for this amino acid.

A new insertion sequence, IS14999, from Corynebacterium glutamicum

Microbiology ◽  
2005 ◽  
Vol 151 (2) ◽  
pp. 501-508 ◽  
Author(s):  
Yota Tsuge ◽  
Kana Ninomiya ◽  
Nobuaki Suzuki ◽  
Masayuki Inui ◽  
Hideaki Yukawa
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Corynebacterium Glutamicum ◽  
Insertion Sequence ◽  
Genetic Manipulation ◽  
Insertion Site ◽  
Amino Acid Sequences ◽  
Transfer Event ◽  
Reading Frame ◽  
Partial Homology

A new insertion sequence from Corynebacterium glutamicum ATCC 14999 was isolated and characterized. This IS element, designated IS14999, comprised a 1149 bp nucleotide sequence with 22 bp imperfect terminal inverted repeats. IS14999 carries a single open reading frame of 345 amino acids encoding a putative transposase that appears to have partial homology to IS642, an IS630/Tc1 superfamily element, at the C-terminal region in the amino acid sequence. This indicated that IS14999 belonged to the IS630/Tc1 superfamily, which was first identified in C. glutamicum. IS14999 has a unique distance of 38 amino acid residues between the second and third amino acids in the DDE motif, which is well known as the catalytic centre of transposase. This suggested that IS14999 constituted a new subfamily of the IS630/Tc1 superfamily. A phylogenetic tree constructed on the basis of amino acid sequences of transposases revealed that this new transposable element was more similar to eukaryotic Tc1/mariner family elements than to prokaryotic IS630 family elements. Added to the fact that IS14999 was present in only a few C. glutamicum strains, this implies that IS14999 was probably acquired by a recent lateral transfer event from eukaryotic cells. Analysis of the insertion site in C. glutamicum R revealed that IS14999 appeared to transpose at random and always caused a target duplication of a 5′-TA-3′ dinucleotide upon insertion, like the other IS630/Tc1 family elements. These findings indicated that IS14999 could be a powerful tool for genetic manipulation of corynebacteria and related species.

SOME VITAMIN AND AMINO ACID INTERRELATIONSHIPS IN ESCHERICHIA COLI 113-3: I. THE INHIBITORY EFFECTS OF CYSTINE AND CYSTEINESULPHINIC ACID

1957 ◽  
Vol 3 (7) ◽  
pp. 967-974 ◽  
Author(s):  
J. M. McLaughlan
Keyword(s):  
Escherichia Coli ◽  
Amino Acids ◽  
Amino Acid ◽  
Glutamic Acid ◽  
Aspartic Acid ◽  
Pantothenic Acid ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Aerobic Conditions ◽  
High Concentrations

Cystine, cysteinesulphinic acid (CSA), and other closely related sulphur-containing amino acids inhibited growth of Escherichia coli 113-3, particularly in aerobic conditions. The cystine inhibition was completely prevented by aspartic acid, partially reversed by pantothenic acid or β-alanine and slightly reversed by lysine or thiamine. The inhibitory effect of CSA was completely or partially reversed by aspartic acid, lysine, glutamic acid, proline, ornithine, or homoserine. Aspartic acid and glutamic acid appeared to reverse the inhibition competitively while lysine seemed to reverse the inhibition in a noncompetitive manner. Reversal of the inhibitory effect of relatively high concentrations of CSA by lysine was not complete, however, unless methionine was also present. Possible mechanisms of the cystine and CSA inhibition are discussed.

scholarly journals Fermentative N-Methylanthranilate Production by Engineered Corynebacterium glutamicum

2020 ◽  
Vol 8 (6) ◽  
pp. 866 ◽  
Author(s):  
Tatjana Walter ◽  
Nour Al Medani ◽  
Arthur Burgardt ◽  
Katarina Cankar ◽  
Lenny Ferrer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Corynebacterium Glutamicum ◽  
Shikimate Pathway ◽  
Product Formation ◽  
Sugar Uptake ◽  
Bioreactor Culture ◽  
Acid Fermentation ◽  
Flavor Compound ◽  
Adenosyl Methionine

The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermentation processes using the Gram-positive bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the aromatic amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing by-product formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in production of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate production. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L−1 with a volumetric productivity of 0.01 g·L−1·h−1 and a yield of 4.8 mg·g−1 glucose.

scholarly journals Diversity of D-Amino Acid Utilizing Bacteria From Kongsfjorden, Arctic and the Metabolic Pathways for Seven D-Amino Acids

2020 ◽  
Vol 10 ◽  
Author(s):  
Yang Yu ◽  
Jie Yang ◽  
Li-Yuan Zheng ◽  
Qi Sheng ◽  
Chun-Yang Li ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Metabolic Pathways
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