Amino acids production
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Amino Acids Production. REXIM S.A. 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)

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Amino Acids Production

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Amino acids production

Amino Acids Production

REXIM S.A.


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 )

Rexim is 100% Degussa since 20 years

REXIM S.A.


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

Processes

REXIM S.A.


L amino acids extraction from proteins hydrolysates 1 8

Serine , Threonine ,

Proline , Hydroxyproline,

Alanine, Valine,

Isoleucine , Leucine

Phenylalanine,

Histidine, Arginine

( asp, glu, gly, lys, tyr ,met)

L-Amino Acids Extraction from Proteins Hydrolysates1/8

REXIM S.A.


Extraction from proteins hydrolysates 2 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

Extraction from Proteins Hydrolysates2/8 :Process

REXIM S.A.


Extraction from proteins hydrolysates 3 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

Extraction from Proteins Hydrolysates3/8

REXIM S.A.


Extraction from proteins hydrolysates 4 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

Extraction from Proteins Hydrolysates4/8

REXIM S.A.


Extraction from proteins hydrolysates 5 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)

Extraction from Proteins Hydrolysates5/8

REXIM S.A.


Extraction from proteins hydrolysates 6 8

Activated mineral Charcoal treatment :

Purification based on surface adsorption :

Charcoal fixes coloured entities and macromolecules ( endotoxines... )

Extraction from Proteins Hydrolysates6/8

REXIM S.A.


Extraction from proteins hydrolysates 7 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

Extraction from Proteins Hydrolysates7/8

REXIM S.A.


Extraction from proteins hydrolysates 8 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 )

Extraction from Proteins Hydrolysates8/8

REXIM S.A.


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

Purification from lower Grade ( feed )

REXIM S.A.


Amino acids production

Enzymatic resolution at KonstanzL- 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

REXIM S.A.


Biocatalysis in china

Fumaric acid + NH3 + fumarase L-aspartic acid

Bioreaction, filtration, precipitation , filtration, drying

L-aspartic + aspartate bdecarboxylaseL-alanine

Bioreaction, filtration, precipitation , filtration, drying

Biocatalysis in China

REXIM S.A.


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

Fermentation in China

REXIM S.A.


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