Abstract Process Economics Program Report 106A AMINO ACIDS (December 2002) Amino acids are the building blocks for protein and essential to all living organisms. They are used as food additives, feed additives and in pharmaceuticals. The amino acid L-glutamic acid, the starting material for the flavor enhancer monosodium glutamate (MSG) is produced at a capacity of nearly 3 billion lb/yr (1,360,000 t/yr). Another amino acid produced in large volume is methionine. The global consumption of amino acid is 880 million lb/yr or (400,000 t/yr). The market for this compound is satisfied by two distinct products, solid D,L-methionine (DLM), its hydroxy analogue, 2-hydroxy 4- (methylthio)butanoic acid (HMBA) a liquid. Other large volume amino acids include L-lysine with a global capacity of 1.5 billion lb/yr (70,000 t/yr) and L-threonine 66 million lb/yr (30,000t/yr) Growth in the feed additives market has been spurred by several factors. One is the outbreak of bovine spongiform encephalopathy (BSE) " mad cow disease" Measures to contain the disease has resulted in a ban on the use of animal derived protein sources by the EU in December of 2000 (106A279). In addition European producers are under increasing environmental pressure to reduce the nitrogen level in wastes. The substitution of amino acids for more complex protein sources can reduce discharge by 20-25%. This report covers the production of D,L-methionine(DLM) and its hydroxy analogue (HMBA), L-threonine, L-glutamic acid and its sodium salt monosodium glutamate (MSG). Processes for L-lysine production has been covered in the following PEP Review 97-8 Lysine-sulfate by fermentation, and PEP Review 97-9, Lysine-HCL by Fermentation with Recovery by Ion-exchange, and in PEP Report 188B, Bioseparation Processes, 2002. This report will be of interest producers of chemicals that are required for methionine production i.e. acrolein, methyl mercaptan and hydrogen cyanide, suppliers of glucose for fermentation and to manufacturers of the amino acids. PEP 02 RGB
CONTENTS 1 INTRODUCTION... 1-1 2 SUMMARY... 2-1 INTRODUCTION... 2-1 METHIONINE PRODUCTS... 2-1 Technical Aspects... 2-1 D,L Methionine (DLM)... 2-1 Methionine Hydroxy Analogue... 2-2 Economic Aspects... 2-2 L-Threonine... 2-4 Technical Aspects... 2-4 MONOSODIUM GLUTAMATE FROM L-GLUTAMIC ACID... 2-4 Technical Aspects... 2-5 Economic Aspects... 2-5 3 INDUSTRY STATUS... 3-1 METHIONINE... 3-1 Products... 3-1 Bioefficacy... 3-1 Manufacturers... 3-2 Novus... 3-3 Degussa... 3-3 Adiesso... 3-3 Sumitomo... 3-4 NEW METHIONINE MARKETS... 3-4 L-THREONINE... 3-4 Intellectual Property Issues... 3-5 L-GLUTAMIC ACID / MONOSODIUM GLUTAMATE... 3-6 iii
CONTENTS (Continued) Pricing... 3-6 4 CHEMISTRY... 4-1 METHIONINE CHEMISTRY... 4-1 MMP Synthesis... 4-2 Synthesis of Hydantoin... 4-3 Hydrolysis of MMEH... 4-4 Recovery of DL-Methionine (DLM)... 4-5 Regeneration of Base... 4-6 METHIONINE HYDROXY ANALOGUE CHEMISTRY... 4-6 MMP Synthesis... 4-7 HMBN Synthesis... 4-8 HMBN Hydrolysis... 4-8 L-Threonine Chemistry... 4-9 L-GLUTAMIC ACID CHEMISTRY... 4-13 Monosodium Glutamate... 4-15 5 METHIONINE HYDROXY ANALOGUE... 5-1 INTRODUCTION... 5-1 PROCESS REVIEW... 5-2 MMP Synthesis... 5-3 HMBN Synthesis... 5-4 HMBN Hydrolysis... 5-5 HMBA Recovery... 5-5 By-Product Recovery / Recycle... 5-6 Hydrolysis of HMBN by Biocatalyst... 5-6 PROCESS DESCRIPTION... 5-9 Process Overview... 5-9 iv
CONTENTS (Continued) SECTION 100... 5-9 MMP Synthesis... 5-9 HMBN Synthesis... 5-10 SECTION - 200... 5-10 HMBN Hydrolysis... 5-10 SECTION - 300... 5-10 HMBA Recovery... 5-10 PROCESS DISCUSSION... 5-20 Raw Material... 5-20 HMBN Production... 5-20 Solvent Recovery... 5-20 Surge Vessels... 5-20 Product Quality... 5-20 WASTE TREATMENT... 5-21 MATERIALS OF CONSTRUCTION... 5-21 CAPITAL AND PRODUCTION COSTS... 5-22 Capital Costs... 5-22 Production Costs... 5-22 DISCUSSION OF CAPITAL COST AND PRODUCT VALUE... 5-22 Capital Costs... 5-22 Waste Treatment... 5-23 Raw Materials... 5-23 Product Value... 5-23 Summary... 5-23 6 D,L-METHIONINE PRODUCTION... 6-1 INTRODUCTION... 6-1 v
CONTENTS (Continued) PROCESS REVIEW... 6-2 Introduction... 6-2 Chemistry... 6-2 Amino-Nitrile Process... 6-3 Hydantoin Process... 6-4 Hydrolysis of MMEH... 6-8 DLM Recovery... 6-9 Regeneration of Base... 6-9 OTHER PROCESSES... 6-10 Biocatalytic Conversion... 6-10 PROCESS DESCRIPTION... 6-10 Introduction... 6-10 PROCESS OVERVIEW... 6-11 Section 100 - MMP Synthesis... 6-11 Section 200 - Hydantoin Synthesis... 6-12 Section 300... 6-12 Potassium Methioninate Formation... 6-12 Methionine Recovery... 6-12 Regeneration of Base... 6-13 Section 400... 6-13 Drying and Packaging... 6-13 PROCESS DISCUSSION... 6-21 MMP Synthesis... 6-21 Hydantoin Hydrolysis... 6-21 Methionine Recovery... 6-21 General Comments... 6-21 SAFETY ISSUES... 6-22 vi
CONTENTS (Continued) PRODUCT FORM... 6-22 MATERIALS OF CONSTRUCTION... 6-23 WASTE GENERATION... 6-23 CAPITAL COSTS... 6-23 Capital Costs... 6-23 Production Costs... 6-23 DISCUSSION OF CAPITAL COST AND PRODUCT VALUE... 6-23 Capital Costs... 6-23 Raw Materials... 6-24 SUMMARY... 6-24 7 L-THREONINE PRODUCTION... 7-1 INTRODUCTION... 7-1 CHEMISTRY... 7-1 Fermentation... 7-2 TECHNOLOGY OVERVIEW... 7-5 Fermentation... 7-5 Ajinomoto... 7-5 Archer-Daniels-Midland... 7-5 Degussa... 7-5 Toray Industries... 7-6 Kyowa Hakko... 7-6 Mitsubishi Petrochemical... 7-6 PROCESS DESCRIPTION... 7-7 Overview... 7-7 Media Preparation... 7-7 Fermentor Sterilization... 7-8 vii
CONTENTS (Continued) Fermentor Inoculation & Culture Growth... 7-8 L-Threonine Production... 7-8 Biomass Separation... 7-9 Purification Section 200... 7-9 L-Threonine Adsorption Zone... 7-10 Elution Wash Zone... 7-10 L-Threonine Elution Zone... 7-11 Backwash Zone... 7-11 Adsorption Wash Zone... 7-11 Recovery - Section 300... 7-11 PROCESS DISCUSSION... 7-18 Fermentation... 7-18 Biomass Separation... 7-18 Ion-Exchange Recovery... 7-18 Product Recovery and Packaging... 7-19 PRODUCT QUALITY AND MARKETS... 7-19 Materials of Construction... 7-19 WASTE STREAMS... 7-19 Gaseous Wastes... 7-19 Aqueous Wastes... 7-19 Solid Wastes... 7-19 Capital Costs... 7-20 Production Costs... 7-20 Discussion of Capital Cost and Product Value... 7-20 Raw Materials... 7-20 8 MSG PRODUCTION L-GLUTAMIC ACID BY FERMENTATION... 8-1 INTRODUCTION... 8-1 viii
CONTENTS (Continued) TECHNOLOGY OVERVIEW... 8-1 CHEMISTRY... 8-2 TECHNOLOGY OVERVIEW... 8-5 Strain Modification... 8-5 Operating Mode... 8-6 By-product Reduction... 8-6 Low ph Fermentation... 8-6 Thermophilic Strain... 8-7 Recovery... 8-7 PROCESS OVERVIEW... 8-16 Overview... 8-16 Section 100 - Fermentation... 8-16 Media Preparation... 8-16 Fermentor Sterilization... 8-16 Fermentor Inoculation & Culture Growth... 8-17 Section 200-GA Recovery... 8-17 Section 300-Product Recovery... 8-18 PROCESS DISCUSION... 8-18 Fermentation... 8-18 Biomass Separation... 8-18 Carbon Treatment... 8-18 Acidification of Broth... 8-19 GA Recovery... 8-19 Recovery of MSG... 8-19 PRODUCT QUALITY AND MARKETS... 8-19 MATERIALS OF CONSTRUCTION... 8-19 WASTE STREAMS... 8-19 ix
CONTENTS (Concluded) Gaseous Wastes... 8-19 Aqueous Wastes... 8-20 Solid Wastes... 8-20 Capital Costs... 8-20 Production Costs... 8-20 Discussion of Capital Cost and Product Value... 8-20 Raw Materials... 8-21 APPENDIX A: PATENT SUMMARY TABLES... A-1 5.1 Methionine Hydroxy Analogue Patent Summary... A-3 6.1 D,L-Methionine Production Patent Summary... A-10 7.1 L-Threonine Production Patent Summary... A-13 8.1 MSG Production L-Glutamic Acid by Fermentation Patent Summary... A-19 APPENDIX B: DESIGN AND COST BASES... B-1 DESIGN CONDITIONS... B-3 COST BASES... B-3 Capital Investment... B-3 Production Costs... B-4 Effect of Operating Level on Production Costs... B-5 APPENDIX C: CITED REFERENCES... C-1 APPENDIX D: PATENT REFERENCES BY COMPANY... D-1 APPENDIX E: PROCESS FLOW DIAGRAM... E-1 x
ILLUSTRATIONS 4.1 L-Methionine... 4-1 4.2 D-Methionine... 4-1 4.3 HMBA... 4-7 4.4 L-Threonine... 4-9 4.5 The Embden-Meyerhof-Parnas Catabolism Pathway... 4-11 4.6 Threonine Metabolic Pathway... 4-12 4.7 L-Glutamic Acid... 4-13 4.8 Tricarboxylic Cycle... 4-14 4.9 Monosodium Glutamate Monohydrate... 4-16 4.10 Monosodium Glutamate Synthesis... 4-16 5.2 D,L-Methionine Hydroxy Analogue (HMBA) Block Flow Diagram... 5-3 5.3 Biocatalytic Conversion HMBN to HMBA Sequential Feed... 5-7 5.4 Biocatalytic Conversion HMBN to HMBA Recirculating Reactor... 5-8 6.2 D,L-Methionine Block Flow Diagram... 6-11 7.1 L-Threonine Structure... 7-2 7.2 The Embden-Meyerhof-Parnas Catabolism Pathway... 7-3 7.3 Threonine Metabolic Pathway... 7-4 7.4 Calgon Carbon Type Simulated Moving Bed Ion-Exchange System... 7-10 8.1 L-Glutamic Acid... 8-2 8.2 Embden-Meyerh of-parnas Pathway... 8-3 8.3 Conversion of KGA to GA... 8-4 xi
TABLES 2.1 Methionine Sources Manufacturing Cost Summary... 2-3 2.2 Amino Acids Manufacturing Cost Summary... 2-6 3.1 D,L-Methionine and Hydroxy Analogue Capacities... 3-2 3.2 Global Methionine Market... 3-2 3.3 World Producers of Threonine... 3-5 3.4 Global Threonine Market - 1999... 3-5 3.5 World MSG Capacity - 1999 (Percent)... 3-6 4.1 Selected Properties of Methionine... 4-2 4.2 Properties of HMBA... 4-7 4.3 Selected Properties of L-Threonine... 4-10 4.4 Selected Properties of L-Glutamic Acid... 4-13 5.2 D,L-Methionine Hydroxy Analogue Production Design Bases and Assumptions... 5-12 5.3 D/L - Methionine Hydroxy Analog Production Stream Flows... 5-14 5.4 Methionine Hydroxy Analogue Production Major Equipment... 5-18 5.5 HMBA Specifications... 5-21 5.6 Methionine Hydroxy Analogue Production Utilities Summary... 5-24 5.7 Methionine Hydroxy Analogue Production Total Capital Investment... 5-25 5.8 Methionine Hydroxy Analogue Production Capital Investment by Section... 5-26 5.9 Methionine Hydroxy Analogue Production Production Costs... 5-27 6.2 D,L-Methionine Production Design Bases and Assumptions... 6-14 6.3 D,L Methionine Production Stream Flows... 6-16 xii
TABLES (Continued) 6.4 DL-Methionine Specifications... 6-22 6.5 D/L-Methionine Production Major Equipment... 6-25 6.6 D/L-Methionine Production Utilities Summary... 6-27 6.7 D/L-Methionine Production Total Capital Investment... 6-28 6.8 D/L-Methionine Production Capital Investment by Section... 6-29 6.9 D/L-Methionine Production Production Costs... 6-31 7.2 L-Threonine Physical Properties... 7-2 7.3 Fermentation Media Composition... 7-7 7.4 Threonine Production Ion Exchange Recovery Process Design Bases and Assumptions... 7-12 7.5 Threonine Production Ion Exchange Recovery Process Stream Flows... 7-14 7.6 L-Threonine Production by Fermentation Recovery by Ion Exchange Major Equipment... 7-16 7.7 L-Threonine Production by Fermentation Recovery by Ion Exchange Utilities Summary... 7-21 7.8 L-Threonine Production by Fermentation Recovery by Ion Exchange Total Capital Investment... 7-22 7.9 L-Threonine Production by Fermentation Recovery by Ion Exchange Capital Investment by Section... 7-23 7.10 L-Threonine Production by Fermentation Recovery by Ion Exchange Production Cost... 7-24 8.2 MSG Production L-Glutamic Acid by Fermentation Design Bases and Assumptions... 8-8 8.3 MSG Production L-Glutamic Acid by Fermentation Stream Flows... 8-10 8.4 Monosodium Glutamate Monohydrate from L-Glutamic Acid Major Equipment... 8-14 xiii
TABLES (Concluded) 8.5 Monosodium Glutamate Monohydrate from L-Glutamic Acid Utilities Summary... 8-22 8.6 Monosodium Glutamate Monohydrate from L-Glutamic Acid Total Capital Investment... 8-23 8.7 Monosodium Glutamate Monohydrate from L-Glutamic Acid Capital Investment by Section... 8-24 8.8 Monosodium Glutamate Monohydrate from L-Glutamic Acid Production Costs... 8-25 xiv