Amino Acids Production

Slide 1:Amino Acids Production 

Slide 2:Rexim is 100% Degussa since 20 years

Headquarter : Courbevoie , France, (Paris) Production Plants for Pharmaceutical Grade L-amino acids : Ham , France Konstanz , Germany Nanning , China (2001) Production Plants for Feed Grade Aminoacids Blair ,Mobile , USA (L-lys ,DL-met) Antwerp , Belgium (DL-met ) Wesseling , Germany ( DL-met ) Slovakia ( L-lys ,L-thr )

Slide 3:Processes

Production Plants for Pharmaceutical Grade L-Amino Acids : Ham , France : Extraction from Proteins hydrolyzates Purification from lower grades ( feed,...) Konstanz , Germany : Enzymatic resolution Nanning , China : Biocatalysis and fermentation Production Plants for Feed Grade Amino acids Synthesis Fermentation

Slide 4:L-Amino Acids Extraction from Proteins Hydrolysates1/8

Serine , Threonine , Proline , Hydroxyproline, Alanine, Valine, Isoleucine , Leucine Phenylalanine, Histidine, Arginine ( asp, glu, gly, lys, tyr ,met)

Slide 5:Extraction from Proteins Hydrolysates2/8 :Process

Selection Purification of natural Proteins Acidic Hydrolysis Filtration Ion exchange chromatographic steps Charcoal treatment (Ultrafiltration) Crystallization 1 Charcoal treatment Ultrafiltration Crystallization 2 ,Drying

Slide 6:Extraction from Proteins Hydrolysates3/8

Selection Purification of natural Proteins and pure Chemicals: Keratins from feathers ( chicken ,ducks ,turkeys ) Gelatin from pigs Bovine free materials Chemicals like NH3, HCl, NaOH, H2SO4,alcohols Regular Suppliers Audits

Slide 7:Extraction from Proteins Hydrolysates4/8

Acidic Hydrolysis of Proteins: Conditions choosen for complete disappearance of proteinic materials : only short peptides (2-4 units ) remain. Use of a large excess of concentrated HCl. Keratin is heated 6 hrs at 105�C Gelatin is heated 4 hrs at 120�C

Slide 8:Extraction from Proteins Hydrolysates5/8

Ion exchange chromatography : Main step achieving separation of single amino acids. Separation based on ionic properties but also on differences on sizes and hydrophobicities ( peptides separated aswell)

Slide 9:Extraction from Proteins Hydrolysates6/8

Activated mineral Charcoal treatment : Purification based on surface adsorption : Charcoal fixes coloured entities and macromolecules ( endotoxines... )

Slide 10:Extraction from Proteins Hydrolysates7/8

Ultrafiltration : Main Purpose is biological purification : removal of endotoxines for making infusion grade amino acids . Done on membranes with cut off of 5000 to 10 000 daltons; Efficiency measured by limulus test. Crystallization : A recognized method for purification as demonstrated by HPLC

Slide 11:Extraction from Proteins Hydrolysates8/8

Biological Safety TSE Expert reports from Pasteur Institute since 1992 Viral Safety Validation report (Pasteur Institute /1998 ) using : Encephalomyocarditis virus Canine Parvovirus classified as ��resistant�� and ��highly resistant�� by the CPMP (Committee for Proprietary Medicinal Products )

Slide 12:Purification from lower Grade ( feed )

Typical examples : asp ,glu , gly ,lys Process uses activated charcoal,ultrafiltration and Recrystallization Origins: asp : bioconversion of fumaric acid glu , lys : fermentation gly : synthesis

Slide 13: Enzymatic resolution at Konstanz L- Methionine1. DL- Methionine -> N-acetyl-DL-Methionine2. acylase -> L-met + N-acetyl-D-Met3. ion exchange separation-> L- Methionine-> N-acetyl-D-Met 4. -> N-acetyl-DL-Methionine

Slide 14:Biocatalysis in China

Fumaric acid + NH3 + fumarase ? L-aspartic acid Bioreaction, filtration, precipitation , filtration, drying L-aspartic + aspartate bdecarboxylase L-alanine Bioreaction, filtration, precipitation , filtration, drying

Slide 15:Fermentation in China

Sugar + Cornsteep + NH3 ? L- Valine Biomass removal, ion exchange ,crystallisation ,filtration, drying Sugar + Cornsteep + NH3 ? L- Isoleucine Biomass removal, ion exchange ,crystallisation ,filtration, drying