Microbial Biotechnology Scope, Technique and Examples in Therapeutics
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The document discusses various applications of microbial biotechnology, particularly in therapeutics, including the production of insulin and human growth hormone through genetic engineering. It highlights advancements such as DNA vaccines, secondary metabolites for drug development, and specific pharmaceuticals like avermectins and taxol, which have important medical uses. Additionally, it explores the significance of compounds like zaragozic acids that target cholesterol biosynthesis and their potential in treating neurodegenerative diseases.
Microbial Biotechnology Scope, Technique and Examples in Therapeutics
- 1. Microbial Biotechnology 1 Microbial Biotechnology Scope, Technique and Examples in Therapeutics 1. Production of heterologous proteins Genetic engineering enables us to produce a large number of proteins in bacterial cell that were originally encoded by human genes. For example a landmark in this case is production of insulin in bacterial cell in 1982. It is first case of genetically engineered therapeutic protein used for clinical purposes. Insulin produced in this way is widely used in curing diabetes and is same in all forms as compared to original insulin Other similar discovery is of hgH (human growth hormone) originally made in pituitary gland in humans. Hormone reduction causes dwarfism in many cases. Traditional ways are difficult and many dangers are associated to their use. For example it may lead to some viral diseases note that genetically engineered hgH is cost effective and safe to use. Other such discoveries by using rDNA technology are the production of TPA (Human tissue plasminogen activator) which has a clot degrading property and is lifesaving drug for curing a acute mycocardail infarction 2. DNA Vaccines A DNA vaccine contains an engineered plasmid DNA on a large scale in the E Coli. They are widely accepted because are not infectious, do not replicate and encode only protein of interests as there is no protein associated with them so they don’t generate an immune response. It consist of a specific promoter for expression e.g. early promoter of cytomegalovirus, a cloning site for the insertion of the gene encoding the antigenic protein; and polyadenylation termination sequence. Plasmid should have an ori (origin of replication) and selectable marker gene too.
- 2. Microbial Biotechnology 2 DNA vaccines are injected by intramuscular injection and antigen express by encoded gene and generate an immune response. Example is for example, the gene encoding gp120, a glycoprotein located on the external surface of HIV. Entire genome can be encoded by using shotgun cloning. DNA vaccines generate both humoral and cellular responses. DNA vaccines are yet not applied on large scale because of some severe side effects related to autoimmunity is identifies. 3. Secondary metabolites as a source of drug Microorganism produced many valuable secondary metabolites in large amount, e.g. antibacterial orantifungal agents, anticancer drugs, etc. screen are applied to check the biological activity of these metabolites. Microbes are engineered to produce these compounds; antibiotics are most important metabolite because of its large applications in human therapeutics and it provide a source of almost 75 % of marketed antimicrobial agents. 4. Avermectins The avermectins are a series of drugs used to treat parasitic worms. They are 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete. S avermitilis produces a family of closely related macrocyclic lactones, compounds that are active against certain nematodes and arthropods at extremely low doses, but have relatively low toxicity to mammals. Avermectins act on invertebrates by activating glutamate-gated chloride channels in their nerves and muscles, disrupting pharyngeal function and locomotion. The paralyzed parasite most likely starves to death. A semisynthetic derivative of avermectin B1a is drug used mass treatment programs to eradicate two widespread
- 3. Microbial Biotechnology 3 serious diseases that affect millions of people and that are caused by nematodes river blindness (onchocerciasis) and lymphatic filariasis. 5. Zaragozic acids (Squalestatin) The 93% cholesterol in human body is present in human cells and 7 % present in plasma and can cause atherosclerosis (plaques on the walls of the arteries supplying the heart, the brain, and other vital organs). Plasma cholesterol is packaged in lipoprotein particles; two thirds is associated with low-density lipoprotein (LDL) and the balance with high-density lipoprotein. Hypercholesterolemia (elevated plasma levels of cholesterol-bearing LDL). Squalene synthase is an attractive target for selective inhibition of cholesterol biosynthesis. Screening of fungal cultures led to the discovery of three structurally related and very potent inhibitors of squalene synthase. Zaragozic acid A was obtained from an unidentified fungus found in a water sample taken from the Jalon River in Zaragoza, Spain, hence the name. Soon after, zaragozic acids B and C were obtained from fungi isolated elsewhere: Sporomiella intermedia, acoprophilous fungus isolated from cotton tail rabbit dung in Tucson, Arizona, and Leptodontium elatius, isolated from wood in a forest in North Carolina Others applications are Squalestatin was shown to cure prion infected neurons(kuru and Creutzfeldt–Jakob disease in humans) and to protect against prion neurotoxicity In prion diseases, the normal cellular prion, PrPc, is converted into a β- sheet–rich conformer, PrPSc, whose aggregation is believed to lead to neuro degeneration. Low concentrations of squalestatin reduced the cholesterol content of the neurons and prevented the formation of PrPSc. 6. Taxol Endophytes are bacterium or fungus that lives within a plant for at least part of its life cycle without causing apparent diseases genetic exchange takes place in both directions between the
- 4. Microbial Biotechnology 4 plant and the endophytes so a valuable gene ecoding a specific group of complex organic compound can transfer to endophytes, taxol gives a proof of this. In human cells, taxol prevents the depolymerization of microtubules during cell division. It has the same effect in fungi. So, in nature, taxol is a fungicide. Taxol is an effective anti-cancer drug, and demand far exceeded the amount that could be produced from the Pacific yew (Taxus brevifolia). High demand leads to extinction of these slow growing plants so a need of commercial production raises e.g. calluses of a specific Taxus cell line are propagated on a simple defined medium to produce taxol (1989). In 1993, a taxol-producing endophytic fungus, Taxomyces andreanae, was discovered in T. brevifolia. Fungal endophytes in a wide variety of higher plants were found to make taxol. In culture, these endophytes make taxol in sub micro gram per liter amounts still a lot of improvement is needed to fulfill the high demand of taxol.