The Chronological Development of the Fermentation Industry PDF

The Chronological Development of the Fermentation Industry. Stage 1: Prior to 1900 Primary Products: Potable alcohol (beer, wine, spirits) and vinegar. Beer Brewing: Emergence of large-scale breweries in the early 1700s. Use of wooden vats and process control innovations such as therm...

The Chronological Development of the Fermentation Industry. Stage 1: Prior to 1900 Primary Products: Potable alcohol (beer, wine, spirits) and vinegar. Beer Brewing: Emergence of large-scale breweries in the early 1700s. Use of wooden vats and process control innovations such as thermometers and heat exchangers. Mid-1800s: The role of yeasts in fermentation was demonstrated by scientists like Cagniard-Latour, Schwann, Kutzing, and Pasteur convinced the scientific world. Hansen's development of pure yeast cultures using single-cell isolation techniques at Carlsberg brewery. Britishers still use mixed culture fermentation for ale. Vinegar Production: Initial production by natural flora in shallow bowls or barrels. The introduction of the "generator," an early aerobic fermenter, improved efficiency by trickling wine or beer over inert materials like charcoal, wood shavings etc. During 1800s to early 1900s, 10% old vinegar was added to pasteurized medium as process control. Stage 2: 1900-1940 New Products: Yeast biomass, glycerol, citric acid, lactic acid, acetone, and butanol. Bakers’ Yeast Production: Recognition of the importance of oxygen in aerobic processes. Development of fed-batch culture to avoid oxygen limitation. Improvement in aeration in the yeast growing medium with steam-cleaned sparging tubes. Acetone-Butanol Fermentation: Developed by Weizmann during WWI, it required aseptic operation standards. Influenced later aseptic aerobic processes and use fermenters made of vertical cylinders with hemispherical tops and bottoms constructed from mild steel. They could be steam sterilized under pressure and were constructed to minimize the possibility of contamination. Solvent fermentations were later defeated by petrochemical feedstock processes. Stage 3: 1940s Onward Penicillin Production: Driven by WWII needs, submerged culture techniques were developed for it being an aerobic fermentation process it was highly prone to contamination. Challenges included sparging with sterile air and mixing viscous broths. Strain-improvement programs and pilot-plant facilities became crucial. Expansion of Antibiotics and Other Products: Screening for microbial products became sophisticated, leading to the production of other antibiotics, vitamins, gibberellin, amino acids, enzymes, and steroid transformations. Bioethanol Initiatives: Started in the mid-1970s by Brazil and the USA to reduce petroleum dependency. Carbohydrates converted by fermentation to ethanol by microbes. The United States of America produced 56 billion liters of bioethanol in 2015 Ongoing efforts to improve processes using cellulose and lignin feedstocks. Stage 4: 1960s-1980s Microbial Biomass Production: Investigated as a protein source for animal feed. Cheaper protein source. Exploration of continuous culture techniques. The pressure jet and pressure cycle fermenters that eliminated the need for mechanical stirring were developed. Development of large fermenters (ICI process), up to 3,000,000 dm³ for culture of Methylophilus methylotrophus with methanol as carbon source Economic Challenges: The ICI Pruteen process was technologically advanced but failed economically due to competition from cheaper protein sources like soybean and fishmeal. Stage 5: 1980s Onward Establishment of very high-value, low-volume products; a stage often referred as “new biotechnology.” Recombinant DNA Technology: Enabled the production of human and mammalian proteins in microorganisms and cultured animal cells, to be used as therapeutics. Classified products as biopharmaceuticals like vaccines, requiring precise production processes. Therapeutic Proteins: The first approved recombinant protein was human insulin in 1982. Approvals followed for human growth hormone, interferons, monoclonal antibodies, recombinant vaccines-hepatitis B, tissue plasminogen activator, and erythropoietin. Monoclonal Antibodies: Initially used for analytical purposes, now established as therapeutic agents produced by both mammalian and microbial cell cultures. Industry Expansion: New microbial products started reaching the marketplace in the late 1980s and early 1990s through conventional process development. During 1980s, four sec.metabolites launched-cyclosporine (immunoregulant) imipenem (a wide spectrum antibiotic) lovastatin, and ivermectin, an antiparasitic drug used to prevent “African River Blindness” as well as in veterinary practice. By 2012, around 220 biopharmaceuticals were approved. Significant contributions from E. coli(31%), yeast(15%), mammalian cell cultures(43%) and 11% other cells. One of the 2012 recombinant products was Elelyso-Gauchers disease. 2005–12 period were dominated by antibody-based products and engineered proteins. Stage 6: Synthetic Biology Advancements in Genomics, Proteomics and Metabolic flux: The sequencing complete genomes, development of computerized systems to store and access the data has enabled the comparison of genomes and the visualization of gene expression in terms of both mRNA and protein profiles, the transcriptome and proteome respectively. Metabolic flux analysis examines the flux of intermediates through pathways and enables the construction of mathematical models. Led to a holistic view of organisms, enabling synthetic biology to optimize fermentation processes. E.g. Corynebacterium glutamicum-lysine overproduction, synthetic strain E.coli – 1,4-butanediol. Systems Biology: Combines molecular biology, biochemistry, and physiology to manipulate entire organism functions. Goal-maximize the yield of the desired product while minimizing that of unwanted metabolites Economic Competitiveness: Synthetic biology aims to make fermentation processes competitive with petrochemical processes for bulk chemical production.  Key Components of a Fermentation Process 1.Media Formulation: Developing suitable media for culturing the process organism. 2.Sterilization: Ensuring sterility of media, fermenters, and ancillary equipment. 3.Inoculum Production: Producing an active, pure culture for inoculation. 4.Fermentation: Growing the organism under optimal conditions for product formation. 5.Product Extraction and Purification: Efficiently extracting and purifying the product. 6.Effluent Disposal: Managing waste produced by the process. Schematic representation of fermentation process  Research and Development Continuous Improvement: Ongoing efforts to improve the process organism, culture medium, and extraction methods. Isolation and Modification: Isolating and modifying producer organisms to enhance productivity. Cultural Requirements: Determining the cultural requirements of organisms for optimal growth and product formation. Production Plant Design: Designing production plants to meet the specific needs of the fermentation process.