A. Streptokinase → II (Clot removal): Bacterial enzyme (from Streptococcus) that dissolves blood clots. Used as thrombolytic in heart attacks.
B. Statins → III (Cholesterol lowering): Inhibit HMG-CoA reductase → reduce cholesterol synthesis. From fungus Monascus purpureus.
C. Lipases → IV (Detergent formulations): Break down fat/oil stains in laundry. Alkaline lipases added to detergents.
D. Cyclosporin A → I (Immunosuppressive): From fungus Trichoderma polysporum. Suppresses T-lymphocyte activation. Prevents organ rejection.
Microorganisms are prolific producers of bioactive compounds used in medicine and industry. Key medical products from microbes: Streptokinase: from Streptococcus bacteria. Modified by recombinant DNA technology to produce 'clot buster' drugs. Dissolves blood clots in myocardial infarction and pulmonary embolism. Cyclosporin A: from Trichoderma polysporum (fungus). Immunosuppressive drug revolutionising organ transplantation. Statins (lovastatin, compactin): from Monascus purpureus (red yeast rice) and Penicillium citrinum. Competitive inhibitors of HMG-CoA reductase. Reduce LDL cholesterol. Antibiotics (penicillin, streptomycin, tetracycline, erythromycin): from fungi (Penicillium) and bacteria (Streptomyces). These products demonstrate how studying microbial metabolism leads to life-saving medicines.
Industrial enzymes produced by microbes have replaced many harsh chemical processes. Key industrial enzymes: Lipases: from bacteria and fungi. Used in: detergents (remove fat stains), food industry (cheese making, margarine production), biofuel production, leather processing. Operate at alkaline pH and low temperatures — suited for laundry use. Proteases: break down proteins. Used in: detergents (remove protein stains — blood, grass), meat tenderising, bread making, cheese ripening. Alkaline proteases (from Bacillus) — most widely used enzyme in detergents. Amylases: break down starch. Used in: bread making, brewing, paper industry, textile desizing. Cellulases: break down cellulose. Used in: textile industry (stonewashing denim without stones), paper pulp processing, biofuel from plant biomass. Pectinases: break down pectin. Used in: fruit juice clarification, coffee processing. Xylanases: used in paper bleaching (replaces chlorine — more eco-friendly).
Statins are the most prescribed class of drugs worldwide, used to reduce cardiovascular risk by lowering blood cholesterol. History: Akira Endo (Japan) discovered compactin (mevastatin) from Penicillium citrinum in 1971 — first statin. Lovastatin from Monascus purpureus (red yeast rice used in Chinese medicine for centuries). Mechanism: competitive inhibition of HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase) — the rate-limiting enzyme in cholesterol synthesis pathway. Less cholesterol synthesised in liver → liver upregulates LDL receptors → more LDL removed from blood → lower blood LDL. Clinical uses: primary and secondary prevention of cardiovascular disease, reducing risk of heart attack and stroke. Side effects: myopathy (muscle pain/weakness), elevated liver enzymes, rarely rhabdomyolysis. Examples: lovastatin (natural), simvastatin, atorvastatin, rosuvastatin (semisynthetic/synthetic).
When a blood vessel is blocked by a clot (thrombus), thrombolytic therapy can dissolve it. Streptokinase: enzyme from Streptococcus bacteria. Mechanism: activates plasminogen → plasmin → plasmin degrades fibrin (clot material). Originally isolated from bacteria, now produced by recombinant DNA technology. Used in: acute myocardial infarction (heart attack), ischaemic stroke, pulmonary embolism, deep vein thrombosis. Limitation: non-specific (dissolves all fibrin including wound-sealing clots) → bleeding risk. tPA (tissue plasminogen activator): human protein produced by recombinant technology. More specific for fibrin-bound plasminogen. Used in ischaemic stroke (within 4.5 hours). Alteplase (recombinant tPA): preferred over streptokinase for stroke due to specificity. Urokinase: another thrombolytic from kidney cells. Contraindications for thrombolytics: recent surgery, recent stroke, active bleeding, uncontrolled hypertension.
Before cyclosporin A (1970s-80s), organ transplantation had poor outcomes due to rejection. Discovery: Jean-Francois Borel (Sandoz) discovered cyclosporin A from soil fungus Trichoderma polysporum in 1969. Clinical introduction ~1983. Mechanism: binds cyclophilin → complex inhibits calcineurin → calcineurin cannot activate NFAT → IL-2 gene not transcribed → T-cells not activated → no transplant rejection. Specifically targets T-lymphocyte activation (cell-mediated immunity) without broadly suppressing other immune functions. Uses: solid organ transplantation (kidney, liver, heart, lung, pancreas), bone marrow transplantation, autoimmune diseases (rheumatoid arthritis, psoriasis, inflammatory bowel disease). Side effects: nephrotoxicity (kidney damage), hypertension, hirsutism, gum hyperplasia, increased infection risk. Transformed 1-year kidney transplant survival from ~50% to ~90%+ — a true revolution in medicine.
Antibiotics are chemical substances produced by microorganisms that inhibit or kill other microorganisms. History: Alexander Fleming discovered penicillin from Penicillium notatum in 1928 (Nobel 1945). Major antibiotics and their sources: Penicillin: Penicillium notatum/chrysogenum. Beta-lactam antibiotic. Disrupts cell wall synthesis. Streptomycin: Streptomyces griseus. First antibiotic for tuberculosis (TB). Chloramphenicol: Streptomyces venezuelae. Inhibits 50S ribosome. Tetracycline: Streptomyces aureofaciens. Broad-spectrum. Erythromycin: Streptomyces erythreus. Macrolide. Cephalosporins: Cephalosporium acremonium (now Acremonium). Vancomycin: Streptomyces orientalis. Last resort for MRSA. Rifampicin: Amycolatopsis rifamycinica. For TB. Most antibiotics are from Streptomyces bacteria or Penicillium fungi — showing the importance of soil microbiology in drug discovery.
Fermentation technology converts cheap substrates (starch, molasses, cellulose) into valuable products using microbes. Food products: Baker yeast (Saccharomyces cerevisiae): bread making (CO2 for leavening), beer/wine fermentation. Toddy: palm sap fermented by naturally occurring yeast. Idli/dosa: fermentation by Leuconostoc mesenteroides (lactic acid bacteria). Cheese: lactic acid bacteria + various fungi (Penicillium for blue/camembert cheese). Single Cell Protein (SCP): microbial biomass (yeast, bacteria, algae) grown on industrial waste → used as protein supplement for humans and animals. Spirulina (cyanobacterium): SCP with high protein, vitamins. Biogas: anaerobic fermentation of organic waste by methanogens → CH4 (methane) + CO2. Bioethanol: fermentation of sugar/starch by Saccharomyces → ethanol → biofuel. Citric acid: Aspergillus niger ferments sugar → citric acid → food preservative and flavouring.
Recombinant DNA technology has revolutionised pharmaceutical production. Human insulin: first approved recombinant drug (1982). Before: pig and cow insulin used (slightly different, caused immune reactions). Eli Lilly produced Humulin using recombinant E. coli. Two-chain protein: A-chain and B-chain expressed separately → combined in vitro. Later: proinsulin expressed as single chain → processed to insulin. Human growth hormone (HGH): produced in E. coli. Previously from cadaver pituitary glands (risk of Creutzfeldt-Jakob disease). Factor VIII: blood clotting factor for haemophilia A. Produced in CHO (Chinese Hamster Ovary) cells. Erythropoietin (EPO): stimulates RBC production. Used for anaemia in kidney disease. Also misused as performance-enhancing drug. Hepatitis B vaccine: HBsAg produced in yeast. Safer than traditional vaccine. tPA, interferon, monoclonal antibodies (Herceptin, Rituximab): all produced by recombinant technology.