Advances In Biotechnology For The Manufacture Of Commodity & Specialty Chemicals (Technical Insights)

Published by: Frost & Sullivan

Published: Jul. 1, 2001

Table of Contents

1. Introduction

1.1 Scope Objectives And Product Spectrum

1.1.1 Objectives

1.1.2 Product Spectrum

1.1.3 Commercial Factors

1.2 Commercial Realities

2. The Biotechnological Revolution

2.1 Advances In Fermentation And Bioprocess Integration

2.1.1 Fermentation

2.1.1.1 The Principles

2.1.1.2 Unit Operations

2.1.1.3 The Bioreactor

2.1.1.4 Scale-Up

2.1.2 Bioprocess Integration

2.1.2.1 Objectives

2.1.2.2 Protein Production—An Example

2.1.2.3 Downstream Processing—Area Of Opportunity

2.1.2.4 Integrated Fermentation/Product Recovery Techniques

2.1.2.5 Enzyme/Cell Recycle

2.1.2.6 Energy Conservation

2.1.2.7 Technical Potential

2.1.3 Resumé

2.2 Genetic Engineering

2.2.1 Definitions

2.2.2 DNA And The Transfer Of Genetic Information

2.2.3 Recombinant DNA Technology (Gene Cloning)

2.2.4 DNA Probe Technology

2.2.5 Polymerase Chain Reaction

2.2.6 Genomics/Proteomics

2.2.6.1 Structural Genomics

2.2.6.2 Gene Sequencing

2.2.6.3 Pharmacogenomics

2.3 Biocatalysis And Chiral Technology

2.3.1 Biocatalysis

2.3.2 Chiral Technology

2.3.2.1 The Principles

2.3.2.2 The Practicalities

2.3.2.3 The Future

2.4 Glycobiology

2.4.1 Introduction

2.4.2 Carbohydrate Therapeutics

2.5 Combinatorial Chemistry

2.5.1 Introduction

2.5.2 1963-99

2.5.3 The Basic Technology

2.5.3.1 The Future

2.6 Chemicals From Animals

2.6.1 Animal Cell Culture And Fusion

2.6.2 Monoclonal Antibodies

2.6.3 Transgenic Animals

2.7 Chemicals From Plants

2.7.1 Ethnopharmacology

2.7.2 Plant Tissue Culture Techniques

2.7.2.1 Introduction

2.7.2.2 Micropropagation

2.7.2.3 Other In Vitro Techniques Not Involving Callus Formation

2.7.2.4 Introduction Variation Via Tissue Culture

2.7.2.5 Protoplast Fusion

2.7.2.6 Commercial Chemical Technology/Production

3. Organic Feedstocks

3.1 Ethanol

3.1.1 Overview

3.1.2 Conventional Production

3.1.3 Improvements Via Biotechnology

3.2 Acetone/Butanol

3.3 Acetic Acid

3.4 Glycerol

3.5 Other Commodity Chemicals And Current Technologies/Commercial Status

3.5.1 Overview

3.5.2 The Brazilian And Us Ethanol Programs

3.5.3 Future Developments

4. Organic Acids

4.1 Citric Acid

4.1.1 Production

4.2 Lactic Acid

4.3 Itaconic Acid

4.4 Gluconic Acid

4.5 Other Organic Acids

4.6 Commercial Status And Prospects

5. Microbial Enzymes

5.1 Overview

5.2 Industrial Enzyme Production

5.2.1 Introduction

5.2.2 Fermentation Options

5.2.3 Enzyme Recovery

5.2.4 Enzyme Purification

5.2.4.1 Membrane Separation Techniques

5.2.4.2 Gel Filtration

5.2.4.3 Ion Exchange

5.2.4.4 Electrophoresis

5.2.4.5 Precipitation Techniques

5.2.5 Finishing Of The Enzyme Product

5.2.6 Advances In The Production Of Enzymes

5.3 Types Of Enzymes

5.3.1 amylases

5.3.2 Proteases

5.3.3 Glucose Isomerase And Isoglucose

5.3.4 Lactases

5.3.5 Penicillin Acylases

5.3.6 Aspartame

5.4 Enzyme Legislation

5.5 Organic Solvent-Based Enzymes

5.6 “Plastic” Enzymes

5.7 Commercial Status And Prospects

6. Amino Acids

6.1 Production Methods And Major Applications

6.1.1 Overview

6.1.2 L-Glutamic Acid

6.1.3 L-Lysine

6.1.4 L-Tryptophan

6.1.5 L-Methionine

6.1.6 L-Cysteine

6.1.7 4-Hydroxy-D-Phenylglycine

6.1.8 L-Aspartate

6.2 Commercial Status

7. Vitamins And Related Compounds

7.1 Vitamin B 12

7.2 Vitamin B 2

7.3 Vitamin C

7.4 Carotenoids

7.5 Other Vitamins

7.6 Commercial Status

8. Antibiotics

8.1 Overview

8.2 Penicillins

8.3 Cephalosporins

8.4 Streptomycin

8.5 Tetracyclines

8.6 Erythromycin

8.7 Polyene Macrolides

8.8 Antibiotic Classes

8.9 Recent Technologies: Recent Antibiotics

8.10 Antibiotic Resistance

8.11 Commercial Status And Technological Potential

9. Other Biopharmaceuticals

9.1 Steroids And Sterols

9.2 Ergot Alkaloids

9.3 Novel Products

9.3.1 Overview

9.3.2 Insulin

9.3.3 Interferons

9.3.4 Human Growth Hormone

9.3.5 Lymphokines And Other Regulating Substances

9.3.6 Therapeutic Enzymes

9.3.7 Monoclonal Antibodies

9.3.8 Vaccines

9.4 Commercial Status: Future Prospects

10. Microbial Pesticides

10.1 Scientific Advantages And Commercial Requirements

10.2 Bacterial Insecticides Based On Bacillus Thuringiensis

10.3 Bacillus Sphaericus And B Popilliae

10.4 Baculoviruses

10.5 The Herbicide (L)-2-Chloropropionate

10.6 Commercial Status

11. Biopolymers

11.1 Microbial Polysaccharides

11.1.1 Overview

11.1.2 Xanthan

11.1.3 Dextran

11.1.4 Miscellaneous Polysaccharides

11.1.5 Catalytic Conversion Of Polysaccharides

11.2 Microbial Polyesters—Environmentally Friendly Plastics

11.2.1 Overview

11.2.2 Poly-B-Hydroxybutyrate (Phb) And Biopol

11.2.3 Polylactic Acid

11.2.4 Protein-Based Polymers

11.3 Commercial Status And Technological Prospects

12. Other Important Microbial Products

12.1 Nucleotides And Related Compounds

12.1.1 Production

12.2 Gibberellins

12.3 Zearalenone

12.4 Triglycerides And Fatty Acids

12.5 Enzyme Inhibitors

12.6 Cyclosporin A And Other Receptor-Binding Compounds

12.7 Biochips

13. Conclusions

13.1 Summary

13.2 Symbols

13.3 Acknowledgments

13.4 Resources

13.5 Additional Reading

List Of Tables

1. Introduction

1.1 Estimates Of Worldwide Capital Investment

1.2 The Impact Of “Modern Biotechnology” On The Pharmaceutical Industry

2. The Biotechnological Revolution

2.1 Sources Of Carbohydrate And Nitrogen For Industrial Fermentations

2.2 Unit Operations For Bioprocessing

2.3 Examples Of Sequenced Microorganism Genomics

2.4 Examples Of Recently Developed Carbohydrate Drugs

2.5 Combinatorial Chemistry Programs In Development

2.6 Established Hairy Root Cultures With Examples Of

Secondary Product Formation

3. Organic Feedstocks

3.1 Breakdown Of Energy Costs In Cellulose To Ethanol Route

3.2 Some Pertinent Characteristics Of C Thermocellum

3.3 Yields Of Products From 90 M 3 Fermenter

4. Organic Acids

4.1 Practical Microbiological Processes For Organic Acid Production

4.2 Volume And Value Of Major Organic Acid Production

5. Microbial Enzymes

5.1 Some Commercially Available Enzymes

5.2 Some Important Industrially Produced Enzymes And Their Application

5.3 Large-Scale Processes Catalyzed By Enzymes In Organic Solvents

5.4 Global Production Of Major Industrial Microbial Enzymes

5.5 Approximate Global Enzyme Market

5.6 Differences In Enzyme Qualities

5.7 Production Of Industrial Enzymes In The Western World

6. Amino Acids

6.1 Production Of Tryptophan By Transformation Of Precursors

6.2 Enzymatic Processes For The Production Of L-Tryptophan

6.3 Mutants For The Production Of Tryptophan By Direct Fermentation With Glucose

6.4 Industrial Production Of Amino Acids

7. Vitamins And Related Compounds

7.1 Volume And Value Of Major Vitamins‘ Production

8. Antibiotics

8.1 Classification Of Major Antibiotics By Chemical Structure

8.2 Drugs Derived From Lmw Fermentations In Early 1990s

9. Other Biopharmaceuticals

9.1 Product Targets For Recombinant DNA Technology

9.2 Human Protein Cloned In E Coli - Some Examples

9.3 Monoclonal Antibodies In Diagnosis

9.4 Leading-Known Biotech Drug Sales (1997)

9.5 US-Based Target Drugs In Development And Approval

9.6 US-Based Biotech Product Types In Development And Approval

10. Microbial Pesticides

10.1 Main Target Insects Susceptible To B Thuringiensis Preparations

10.2 Principal Baculovirus Candidates For Insect Pest Control

10.3 Potential Substitution Of Chemical Pesticides By Microbial Control Agents In The US

11. Biopolymers

11.1 Accumulation Of Polyhydroxyalkanoates In Various Bacteria

11.2 Western European Market Estimate For Biodegradable Plastics

12. Other Important Microbial Products

12.1 Production By Fermentation Of Substances Related To Nucleic Acids

12.2 Nucleotide Nucleoside And Related Compound Manufacture In Japan

12.3 Protease Inhibitors

List Of Figures

2. The Biotechnological Revolution

2.1 Centrally Stirred Bioreactors

2.2 The Replication Of DNA

2.3 Recombinant DNA: The Technique Of Recombining Genes From One Species With Those Of Another

2.4 Principles Of Monoclonal Antibody Technology

6. Amino Acids

6.1 Flow Diagram For The Continuous Production Of L-Amino Acids By Immobilized Aminoacylase

6.2 Schematic Drawing Of A Two-Phase Membrane Reator

9. Other Biopharmaceuticals

9.1 The Principle Of Human Insulin Production By Recombinant DNA Technology

Abstract

Enabling technologies such as genetic and enzymic transformations, genomics, proteomics, bioprocess integration, combinatorial chemistry, chiral technology, and so forth are presented in relation to the chemical entities whose production they facilitate. These innova-tive technologies are increasingly achieving targets within a more commercially viable environment. Assessments of current and potential commercial realities are made where such information is available, as are current and future market trends.

Although primarily concerned with microbial products, both plant and animal cell culture advances are discussed, principally in relation to both pharmaceuticals and nutraceuticals in the former case and novel biopharmaceuticals in the latter.

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