Report No. 106

AMINO ACIDS

by WING S. FONG

Contributions by Victor E. Althouse

November 1976

A private report by the

PROCESS ECONOMICS PROGRAM

0 I STANFORD RESEARCH INSTITUTE

I MENLO PARK, CALIFORNIA

For detailed marketing data and information, the reader is

referred to one of the SRI programs specializing in marketing

research. The CHEMICAL ECONOMICS HANDBOOK Program covers

most major chemicals and chemical products produced in the

United States and the WORLD HYDROCARBONS Program covers major

hydrocarbons and their derivatives on a worldwide Basis. In

addition, the SRI DIRECTORY OF CHEMICAL PRODUCERS services

provide detailed lists of chemical producers by company,

product, and plant for the United States and Western Europe.

ii

TABLE OF CONTENTS

1 INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2 SUMMARY ............................. 3

Glutamic Acid and Monosodium Glutamate ............. 3 L-Lysine ............................ 4 DL-Methionine and Methionine Hydroxy Analogue ......... 7

3 INDUSTRY STATUS ........................ 9

Monosodium Glutamate ...................... 9 Methionine ........................... 10 Lysine ............................. 18

4 GLUTAMIC ACID AND MONOSODIUM GLUTAMATE BY FERMENTATION ..... 23

Biochemistry .......................... 23 Review of Processes Composition of Medium

..................... 25 .................... 26

Microorganisms ....................... 26 Carbon Sources ....................... 55 Nitrogen Sources ...................... 57 Inorganic Salts Biotin and Other Growth Factors

............... 57 .............. 57

Other Additives ...................... 58 Fermentation ......................... 59

Aeration and Agitation ................... 59 Yield and By-Product .................... 59 Fermenters ......................... 60 Continuous Process ..................... 60 Recovery and Purification ................. 61

Process Description ...................... 62 Process Discussion ....................... 69 Cost Estimates .......................... 71

5 GLUTAMIC ACID AND MONOSODIUM GLUTAMATE BY

Introduction .............. Chemistry From Acrylonitrile. .................... From Acrolein

Review of Processes ........... ..........

Process Description .......... Process Discussion ........... Cost Estimates .............

CHEMICAL SYNTHESIS . . 79

............ 79

............ 79

............ 79

............ 91

............ 92

............ 103

............ 113

............ 115

Vii

TABLE OF CONTENTS

6 L-LYSINE BY FERMENTATION .................... 125

Introduction .......................... 125 Biochemistry .......................... 125 Review of Processes Composition of Medium

..................... 129 .................... 129

Microorganisms ...................... 129 Carbon Sources ....................... 142 Additives ......................... 144

Fermentation ......................... 145 Recovery and Purification ................... 146 Equipment ........................... 147

Process Description ...................... 147 Process Discussion ....................... 153 Cost Estimates ......................... 154

7 L-LYSINE BY CHEMICAL SYNTHESIS ................. 163

Introduction .......................... 163 Chemistry............................16 3 Review of Processes ...................... 174 Process Description ...................... 190 Process Discussion ....................... 201 Cost Estimates ......................... 203

8 DL-METHIONINE AND METHIONINE HYDROXY ANALOGUE ......... 215

Introduction .......................... 215 Chemistry............................21 6 Review of Processes ...................... 219 From Acrolein From Other Materials.

......................................... 232 . 234

DL-Methionine Process Description

...................... 235 ...................... 235

Process Discussion ...................... 243 Cost Estimates ........................ 244

Calcium Salt of Methionine Hydroxy Analogue .......... 253 Process Description ..................... 253 Process Discussion ...................... 261 Cost Estimates ........................ 262

Economic Comparison of DL-Methionine and Calcium Salt of Methionine Hydroxy Analogue .................. 263

APPENDIX DESIGN AND COST BASIS . . . . . . . . . . . . . . . . . . 271

CITED REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . 273

PATENT REFERENCES BY COMPANY . . . . . . . . . . . . . . . . . . . 313

viii

4.1

4.2

4.3

4.4

5.1

5.2

5.3

5.4

6.1

6.2

6.3

6.4

ILLUSTRATIONS

Glutamic Acid Fermentation Pathway . . . . . . . . . . . . . . 24

Monosodium Glutamate by Fermentation Flow Scheme . . ' . . . . . . . . . . . . . . . . . . . . . . 327

Monosodium Glutamate by Fermentation Effect of Molasses Price, Chemical, Nutrient and Packaging, Labor, Capital and Utilities Costs or Requirements and Process Yield on Production Cost . . . . . . . . . . . . . . . . . . 77

Monosodium Glutamate by Fermentation Effect of Operating Level and Plant Capacity on Production cost............................. 78

Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Flow Scheme . . . . . . . . . . . . . . . . , . . . . . . . . 331

Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Effect of Acrylonitrile, Sodium Hydroxide, Sulfuric Acid and Synthesis Gas Prices and By-Product Disposal Charge on Production Cost , , , , , , , . , , , , , , , . , , , , , , . 121

Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Effect of Labor, Capital and Utilities Cost or Requirement and Process Yield on Production Cost . . . . . . . . . . . . 122

Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Effect of Operating Level and Plant Capacity on Production Cost . . . . . . . . . . . . . . . . . . . . . . . . . . ..23

L-LySine Fermentation Pathway via o-Aminoadipic Acid . . . . . 126

L-Lysine Fermentation Pathway via Diaminopimelic Acid, and Feedback Regulation . . . . . . . . . . . . . . . . . . . . . 127

L-Lysine by Fermentation Flow Scheme . . . . . . . . . . . . . . . . . . . . . . . . . 335

L-Lysine by Fermentation Effect of Molasses, Hydrolyzed Soybean Meal, and Aqua Ammonia Prices, Labor, Capital and Utilities Costs or Requirements and Process Yield on Production Cost . . . . . . . . . . . . 160

ix

6.5

7.1

7.2

7.3

7.4

8.1

8.2

8.3

8.4

8.5

ILLUSTRATIONS

L-Lysine by Fermentation Effect of Operating Level and Plant Capacity on Production cost . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization Flow Scheme . . . . . . . . . . . . . . . . . . . . . . . . . 337

L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization Effect of Raw Material Prices on Production Cost . . . . . .

L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization Effect of By-Product (Ammonium Sulfate) Credit and Labor, Capital, Utilities and Nutrients Prices and Requirements on Production Cost . . . . . . . . . . . . . . . . . . . . . .

L-Lysine from Cyclohexene, Using:Cyclohexanol and Enzyme-

Hydrolysis/Racemization

212

213

Effect of Operating Level and Plant Capacity on Production cost . . . . . . . . . . . . . . . . . . . . . . . . . . . . 214

DL-Methionine Flow Scheme . . . . . . . . . . . . . . . . . . . . . . . . . 343

DL-Methionine Effect of Various Raw Materials Prices and By-Product Disposal Charge on Production Cost . . . . . . . . . . . . . 250

DL-Methionine Effect of Labor, Capital or Utilities Cost or Requirement and Process Yield on Production Cost . . . . . . . . . . . . . . 251

DL-Methionine Effect of Operating Level and Plant Capacity on Production cost . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252

Calcium Salt of Methionine Hydroxy Analogue Flow Scheme . . . . . . . . . . . . . . . . . . . . . . . . . 345

X

ILLUSTRATIONS

8.6 Calcium Salt of Methionine Hydroxy Analogue Effect of Acrolein, Methyl Mercaptan and Hydrogen Cyanide Prices and By-Product Disposal Charge on Production Cost . . . 268

8.7 Calcium Salt of Methionine Hydroxy Analogue Effect of Labor, Capital or Utilities Cost or Requirement and Process Yield on Production Cost . . . . . . . . . . . . 269

8.8 Calcium Salt of Methionine Hydroxy Analogue Effect of Operating Level and Plant Capacity on Production Cost . . . . . . . . . . . . . . . . . . . . . . . . . . . ,270

xi

TABLES

-

a -

l

2.1

3.1

3.2

3.3

4.1

4.2

4.3

4.4

4.5

4.6

4.7

4.8

5.1

5.2

Cost Estimate Summary . . . . . . . . . . . . . . . . . . . . 5

MSG Producers . . . . . . . . . . . . . . . . . . . . . . . . 11

DL-Methionine Producers . . . . . . . . . . . . . . . . . . . 16

L-Lysine Monohydrochloride Producers . . . . . . . . . . . . 21

Glutamic Acid and Monosodium Glutamate by Fermentation Patent Summary . . . . . . . . . . . . . . . . . . . . . . . 27

Recovery and Purification of Glutamic Acid and Monosodium Glutamate Obtained by Fermentation Patent Summary . . . . . . . . . . . . . . . . . . . . . . . 47

Monosodium Glutamate by Fermentation Major Equipment and Utilities Summary . . . . . . . . . . . . 65

Monosodium Glutamate by Fermentation Stream Flows . . . . . . . . . . . . . . . . . . . . . . . . 67

Monosodium Glutamate by Fermentation Total Capital Investment . . . . . . . . . . . . . . . . . . 73

Monosodium Glutamate by Fermentation Battery Limits and Utilities Cost by Process Section . . . . 74

Monosodium Glutamate by Fermentation Total Production Cost . . . . . . . . . . . . . . . . . . . . 75

Monosodium Glutamate by Fermentation Total Direct Operating Cost by Process Section . . . . . . . 76

Glutamic Acid and Monosodium Glutamate by Chemical Synthesis Patent Summary . . . . . . . . . . . . . . . . . . . . . . . 8o

Recovery, Purification, Resolution, and Racemization of Glutamic Acids and Sodium Glutamates Obtained by Chemical Synthesis Patent Summary . . . . . . . . . . . . . . . . . . . . . . . 93

xiii

TABLES

5.3 Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Design Bases and Assumptions . . . . . . . . . . . . . . . . 107

5.4 Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Major Equipment and Utilities Summary . . . . . . . . . . . 108

5.5 Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Stream Flows . . . . . . . . . . . . . . . . . . . . . . . . 110

5.6 Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Total Capital Investment . . . . . . . . . . . . . . . . . . 117

5.7 Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Battery Limits and Utilities Cost by Process Section . . . . 118

5.8 Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Total Production Cost . . . . . . . . . . . . . . . . . . . 119

5.9 Monosodium Glutamate by Chemical Synthesis from Acrylonitrile Total Direct Operating Cost by Process Section . . . . . . . 120

6.1 L-Lysine by Fermentation Patent Summary . . . . . . . . . . . . . . . . . . . . . . . 131

6.2 L-Lysine by Fermentation Major Equipment and Utilities Summary . . . . . . . . . . . 149

6.3 L-Lysine by Fermentation Stream Flows . . . . . . . . . . . . . . . . . . . . . . . . 151

6.4 L-Lysine by Fermentation Total Capital Investment . . . . . . . . . . . . . . . . . . 156

6.5 L-Lysine by Fermentation Battery Limits and Utilities Cost by Process Section . . . . 157

xiv

TABLES

6.6 L-Lysine by Fermentation Total Production Cost . . . . . . . . . . . . . . . . . . . 158

6.7 L-Lysine by Fermentation Total Direct Operating Cost by Process Section . . . . . . 159

7.1 Lysine by Chemical Synthesis Patent Summary . . . . . . . . . . . . . . . . . . . . . . 175

7.2 Purification, Resolution and Racemization of Lysine Obtained by Chemical Synthesis Patent Summary . . . . . . . . . . . . . . . . . . . . . . 184

7.3 L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization

Design Bases and Assumptions . . . . . . . . . . . . . . . 194

7.4 L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization

Major Equipment and Utilities Summary . . . . . . . . . . . 195

7.5 L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization

Stream Flows . . . . . . . . . . . . . . . . . . . . . . . . 198

7.6 L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- HydrolysisfRacemization Total Capital Investment . . . . . . . . . . . . . . . . . 206

7.7 L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization Battery Limits, Utilities and Tankage Investment by Process Section . . . . . . . . . . . . . . . . . . . . . . . . . 207

7.8 L-Lysine from Cyclohexene, Using Cyclohexanol and Enzytne- HydroLysis/Racemization

Total Production Cost . . . . . . . . . . . . . . . . . . . 209

7.9 L-Lysine from Cyclohexene, Using Cyclohexanol and Enzyme- Hydrolysis/Racemization

Total Direct Operating Cost by Process Section . . . . . . 210

xv

TABLES

8.1

8.2

8.3

8.4

8.5

8.6

8.7

8.8

8.9

8.10

8.11

8.12

8.13

DL-Methionine and Methionine Hydroxy Analogue or its Salts by Chemical Synthesis Patent Summary , . . . . . . . . . . . . . . . . . . . . . .

DL-Methionine Design Bases and Assumptions . . . . . . . . . . . . . . . .

DL-Methionine Major Equipment and Utilities Summary . . . . . . . . . . .

DL-Methionine Stream Flows . . . . . . . . . . . . . . . . . . . . . . . .

DL-Methionine Total Capital Investment . . . . . . . . . . . . . . . . . .

DL-Methionine Battery Limits and Utilities Cost by Process Section . . .

DL-Methionine Total Production Cost . . . . . . . . . . . . . . . . . . .

DL-Methionine Total Direct Operating Cost by Process Section . . . . . .

Calcium Salt of Methionine Hydroxy Analogue Design Bases and Assumptions . . . . . . . . . . . . . . . .

Calcium Salt of Methionine Hydroxy Analogue Major Equipment and Utilities Summary . . . . . . . . . . .

Calcium Salt of Methionine Hydroxy Analogue Stream Flows . . . . . . . . . . . . . . . . . . . . . . . .

Calcium Salt of Methionine Hydroxy Analogue Total Capital Investment . . . . . . . . . . . . . . . . . .

Calcium Salt of Methionine Hydroxy Analogue Battery Limits and Utilities Cost by Process Section . . . .

220

238

239

241

246

247

248

249

256

257

259

264

265

xvi

TABLES

8.14 Calcium Salt of Methionine Hydroxy Analogue Total Production Cost . . . . . . . . . . . . . . . . . . . 266

8.15 Calcium Salt of Methionine Hydroxy Analogue Total Direct Operating Cost by Process Section . . . . . . 267

xvii