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An overview of the industrial production and applications of amino acids, with a focus on l-glutamine and glutamic acid. It covers the history of amino acid production, worldwide consumption and demand, major uses in research and analytical applications, medical and pharmaceutical uses, and manufacturing methods. The document also discusses the effects of different dissolved oxygen (do) levels on glutamate fermentation and the metabolic balance between glycolysis, glutamate synthesis, and tca metabolic flux.
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Kusumoto I., J ournal of Nutrition. 2001 ; 131:2552-2555.
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Kusumoto I., J ournal of Nutrition. 2001 ; 131:2552-2555.
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Table 1 - Major uses of glutamic acid and its derivatives in research PROTEIN ENGINEERING Peptide synthesis Protein modification Polymer supports BIOCHEMICAL/CELL BIOLOGY Biochemical experiments Cell biology research ANALYTICAL APPLICATIONS Analytical standards Diagnostic products and procedures
Table 2 - Analytical uses of glutamic acid and its derivatives Gas chromatography
Pure glutamic acid or derivatives
Research, medical, food processing Affinity chromatography
Glutamic acids bonded to polymer and other types
Separating complex proteins/high molecular weight materials Radioisotope tracers
Radiolabelled liquid or solid
Medical, pharmaceutical
Table 3 - Medical and pharmaceutical applications TREATING DISEASE Parenteral nutrition, Prescription dietary supplements, Congenital metabolic diseases, Hypertension, Neuroregulators, Ophthalmic solutions DIAGNOSING DISEASE (^) Congenital metabolic diseases, Disorders or malfunction of brain/nervous system
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ENTERAL NUTRITION Crystalline glutamic acid in solution: It is the source of protein precursors for hospitalized patients unable to eat or eat enough to get or stay healthy.
PARENTERAL NUTRITION
Crystalline glutamic acid in solution: Given to the patient through circulatory system via a vein
PRESCRIPTION DIETARY SUPPLEMENTS
Tablet, capsule or powder protein precursors: For people able to eat but who need very highly concentrated source to recover from illness or surgery
CONGENITAL METABOLIC DISEASES Powder Prescription diets: For newborn babies and others who need a diet devoid of or with highly reduced content of specific amino acid
HYPERTENSION (Capsules or injection)
Prescription drugs that reduce blood pressure
NEURO-REGULATORS (Capsules or injection)
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General manufacturing process
The manufacturing methods of amino acids are-
Extraction from acid hyrolysates Chemical synthesis Fermentation Enzymatic
Leucine, proline, tyrosine, cystine are manufactured by extraction, fermentation and chemical synthesis
L-Glutamic acid is manufactured world wide using fermentation
The manufacturing process of an amino acid by fermentation comprises fermentation, crude isolation and purification processes.
In the crude isolation process, most impurities contained in the fermentation broth are removed by combining various technologies
Contd…..
Kusumoto I., J ournal of Nutrition. 2001 ; 131:2552-2555.
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Final purification is performed to ensure the required quality for the intended use
The final product is obtained as a crystalline powder
The product is released only after quality tests have verified that the product meets specific requirements, and the normal functioning of each process step has been verified
All manufacturing processes for the production of amino acids for medical use must comply with current good manufacturing practice requirements
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Schematic representation of glutamic acid production
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Strains producing glutamic acid
Kusumoto I., J ournal of Nutrition. 2001 ; 131:2552-2555.
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Kusumoto I., J ournal of Nutrition. 2001 ; 131:2552-2555.
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Seed culture
Main culture
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Fermented broth Centifugation Collect supernatant
Concentration Ion exchange treatment
Direct Crystallization Resin preparation
Column packing
Separation of fluid (acidified to pH 3.2, with 1 N HCl. Storage at 20°C for 48 h)
Crystallization
K. Madhavan Nampoothiri et al; Revista de microbiologta. 1999; 30.
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Flow diagram of the isolation process.
Kusumoto I., J ournal of Nutrition. 2001 ; 131:2552-2555.
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Effect of temperature on solubility of glutamate
Kusumoto I., J ournal of Nutrition. 2001 ; 131:2552-2555.
