Abstract Process Economics Program Report 188B BIOTECHNOLOGY SEPARATION PROCESSES (June 2002)

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Caren Wilkins
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1 Abstract Process Economics Program Report 188B BIOTECHNOLOGY SEPARATION PROCESSES (June 2002) The chemical industry has a renewed interest in developing processes for producing industrial chemicals from bio-based or renewable feedstocks. Important trends that are driving this interest include the concern over global warming caused by petrochemicals and also the concept of sustainability through the use of renewable resources. Recent technology developments have also provided a better means for utilizing bio-based feedstocks. Genetic engineering has enabled fermentation processing to be a more efficient means of production. Currently, the most important industrial products made using fermentation are ethanol, carboxylic acids, amino acids and enzymes. Fermentation processes used for making industrial biotech products such as lactic acid present unique separation and purification challenges. Product recovery from fermentation broth typically involves the separation of one low concentration component from a large quantity of water and other impurities. This report reviews recent technical advances made in downstream unit operations unique to biotechnology processes such as cell harvesting, biomass removal, extraction, adsorption (chromatography), and electrodialysis. It is an update of the same topic that was reviewed in PEP Report 188A issued in The conventional fermentation process for making lactic acid is difficult to scale-up due to the large quantity of salt wastes that are generated. Several new separation developments are underway that promise to allow large scale lactic acid production at more efficient process economics by avoiding the generation of salt waste. Extraction is one of the most promising of these technologies. This PEP Report provides a detailed technical and economic evaluation of newly developed extraction separation processes for making lactic acid. A major technology shift in amino acid recovery has occurred with the adoption of continuous ion-exchange technology and the abandonment of large, batch ion-exchange resin beds formerly used. In 1990 the first industrial scale continuous ion exchange unit for lysine purification was installed. It is estimated that 75% of all installed lysine capacity uses the new technology. Advantages claimed by the manufacturer of one system are reduced resin requirements through improved resin productivity, reduced wash water use, higher recovery, and reduced waste generation. We evaluate the process economics for making lysine by continuous ion exchange in this PEP Report. For those in the chemical industry, this report will be useful for understanding the unique challenges associated with separating and recovering fermentation products on an industrial scale. In many cases, the cost of separating fermentation products can amount to over half of the total capital and production costs. The report provides a number of examples from prior PEP Reports to present insights into why this is true. Separation technology trends are reviewed with the analysis of over 50 recent patents in the field. PEP 01 GMB

2 CONTENTS 1 INTRODUCTION SUMMARY Separation Processing Considerations Removal of Insolubles Recovery Purification Polishing Cell Harvesting / Biomass Removal Extraction Adsorption Electrodialysis Separation Process Evaluations Lactic Acid Recovery by Extractions L-Lysine HCI Recovery by Ion Exchange ECONOMIC ASPECTS SEPARATION PROCESSING CONSIDERATIONS INTRACELLULAR VERSUS EXTRACELLULAR PRODUCTS GENERAL SEPARATION STEPS Removal of Insolubles Cell disruption (intracellular) Removal of insolubles (intracellular) Recovery Purification Polishing CARBOXYLIC ACIDS Citric Acid TYPICAL BIOTECHNOLOGY SEPARATION PROCESSES iii

3 CONTENTS (Continued) ETHANOL Lactic Acid AMINO ACIDS L-Lysine ENZYMES POLYHYDROXYBUTYRATE-VALERATE CAPITAL COSTS CELL HARVESTING / BIOMASS REMOVAL FILTRATION Mycelia Filtration Yeasts Filtration Bacteria Filtration Rotary Filters Membrane Filters Ultrafiltration Nanofiltration Centrifugation EXTRACTION CARBOXYLIC ACID EXTRACTION ENZYME EXTRACTION EXTRACTION EQUIPMENT Gravity Extractors Centrifugal Extractors PROCESS ECONOMICS Section Fermentation Section Recovery iv

4 CONTENTS (Continued) Section Base Recovery PROCESS DISCUSSION Fermentation Biomass Recycle Extraction Product Quality Materials of Construction Waste Treatment Capital and Production Costs ADSORPTION ADSORBENTS CARBOXYLIC ACID ADSORPTION AMINO ACID ADSORPTION PROCESS ECONOMICS Section Fermentation Media Preparation Fermentor Sterilization Fermentor Inoculation L-lysine Production Section Ion Exchange The L-lysine Adsorption Zone The Elution Wash Zone The L-Lysine Elution Zone The Backwash Zone The Adsorption Wash Zone Section Recovery Concentration and Crystallization v

5 CONTENTS (Continued) PROCESS DISCUSSION Fermentation Fermentor Operating Mode Biomass Recycling Biomass Separation Ion-Exchange Recovery Product Recovery and Packaging Other Recovery Technologies Product Quality and Markets Materials of Construction Waste Streams Biomass Solid Wastes Capital and Production Costs Product Value Capital-Related Items: Maintenance, Taxes and Insurance, Depreciation, ROI Raw Materials ELECRODIALYSIS LACTIC ACID RECOVERY SUCCINIC ACID RECOVERY PROCESS ECONOMICS Selection of Fermentation Design Patent Selection of Electrodialysis Design Patent Maintenance Waste Treatment Capital and Production Costs Discussion of Costs vi

6 CONTENTS (Concluded) APPENDIX A: PATENT SUMMARY TABLES... A-1 APPENDIX B: DESIGN AND COST BASES... B-1 APPENDIX C: CITED REFERENCES... C-1 APPENDIX D: PATENT REFERENCES BY COMPANY... D-1 APPENDIX E: PROCESS FLOW DIAGRAM... E-1 vii

7 ILLUSTRATIONS 3.1 Fermentation Microorganisms General Biotechnology Separation Scheme Ethanol Recovery Citric Acid Recovery Lactic Acid Recovery Lysine HCL Recovery Extracellular Enzyme Recovery Polyhydroxybutyrate-Valerate Recovery Rotary Vacuum Filter Membrane Configurations for Tangential Flow Filtration Critical Flux as Function of Crossflow Velocity Membrane Flux as Function of TMP Ultrafiltration System Capital Cost Common Centrifuge Configurations Purchase Cost of Disk-Stack Centrifuge Citric Acid Recovery by Direct Extraction Lactic Acid Extraction with Carbon Dioxide as Acidulant Lactic Acid Extraction from Low PH Fermentation Broth Continuous Lactic Acid Fermentation Lactic Acid Separation by Membrane-Based Extraction Enzyme Purification by Liquid-Liquid Extraction Protein Partition into Reverse Micelles Penicillin Extractors with Amyl Acetate Differential Extractions Podbielniak Centrifugal Extractor Lactic Acid Recovery By Extraction... E Solute Concentrations in Elution Chromatography viii

8 ILLUSTRATIONS (Concluded) 7.2 Adsorption Isotherms Lactic Acid Recovery by Adsorption PH Effect on Lactic Acid Sorption Isotherms L-Lysine Separation by Simulated Moving Bed Adsorption Lysine-HCL by Fermentation Recovery By Ion-Exchange... E The Isep TM System Details of the Isep TM System Ammonium Lactate Electrodialysis Electrodialysis Processes for Lactic Acid Recovery Principles of Multi-compartment Water Splitting Electrodialysis A.E. Staley's Salt Splitting Electrodialysis Process MBI's Two Stage Succinic Acid Electrodialysis Process ix

9 TABLES 2.1 Chemicals by Fermentation Manufacturing Cost Summary Physical Properties and Separation Techniques Molecular Compositions of a Typical Bacterium Typical Product Concentrations Capital Costs of Fermentation Processes Typical Particle Sizes Categories of Membrane Filters Cell Harvesting/Biomass Removal Patent Summary... A Microfiltration and Ultrafiltration of E. Coli Broth Lactic Acid Flux Rates Using Ceramic Membranes Centrifuge Characteristics Nozzle Centrifuge* Performance Axial Solid Ejecting Centrifuge* Performance Extraction Patent Summary... A Dissociation Constants of Carboxylic Acids at 25 o C Partition Coefficients of Selected Solvents at 37 o C Diluent Effect on Extraction of Citric Acid Enzyme Extraction by Aqueous Two Phase Systems Typical Throughput Capacities for Differential Extractors Pod Contactor Fermentation Broth Extraction Capacities Lactic Acid Recovery by Extraction Design Bases and Assumptions Lactic Acid Recovery by Extraction Stream Flows Lactic Acid Recovery by Extraction Major Equipment x

10 TABLES (Continued) 6.11 Lactic Acid Recovery by Extraction Utilities Summary Recovery of Sodium Lactate by Alamine 336 /Organic Mixture Carbon Dioxide Generation Lactic Acid Recovery by Extraction Total Capital Investment Lactic Acid Recovery by Extraction Capital Investment by Section Lactic Acid Recovery by Extraction Production Costs Lactic Acid Recovery by Extraction Direct Costs by Section, $ thousands/yr Selected Adsorbents Commercial Basic Adsorbents Lactic Acid Recovery Using Weak Base Sorbents Adsorption Patent Summary... A Fixed Bed Versus Isep Lysine Recovery Lysine Production Ion-Exchange Recovery Process Design Bases and Assumptions L-Lysine-HCL by Fermentation Recovery by Ion-Exchange Stream Flows Lysine-Monohyrogenchloride by Fermentation Recovery by Ion Exchange Major Equipment Lysine-Monohyrogenchloride by Fermentation Recovery by Ion Exchange Utilities Summary Lysine-Monohyrogenchloride by Fermentation Recovery by Ion Exchange Total Capital Investment Lysine-Monohyrogenchloride by Fermentation Recovery by Ion Exchange Capital Investment by Section Lysine-Monohyrogenchloride by Fermentation Recovery by Ion Exchange Production Costs xi

11 TABLES (Concluded) 7.13 Lysine-Monohyrogenchloride by Fermentation Recovery by Ion Exchange Direct Costs by Section, $ thousands / yr Succinic Acid by Fermentation Design Bases Succinic Acid Waste Streams Succinic Acid Battery Limits Investment (BLI) xii

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