Int.J.Curr.Microbiol.App.Sci (2015) 4(4): 17-26 ISSN: 2319-7706 Volume 4 Number 4 (2015) pp. 17-26 http://www.ijcmas.com Review Article Overview of Microbial Therapeutic Enzymes Prajakta Mane and Vidya Tale* Department of Microbial Biotechnology, Rajiv Gandhi Institute of IT & Biotechnology, Bharati Vidyapeeth Deemed University, Pune, India *Corresponding author A B S T R A C T Enzymes possess specificity, greater affinity, and high catalytic efficiency. They are required for many chemical inter conversions that support life and speed up all the metabolic processes. These entire characteristics discern them from all other K e y w o r d s types of drugs. Due to these, enzymes are widely been used for different therapeutic purposes and enzyme therapies are acquiring much attention. Both Enzymes, digestive and metabolic enzymes can be used either separately or in combination Therapeutic, with other therapies for the treatment of several diseases such as leukemia, skin Digestive, ulcers, Pompe s disease, cardiovascular diseases, celiac disease, Parkinson s Metabolic, disease, Fabry s disease, inflammation, digestive disorders, pancreatic disorders Drugs etc. They are also employed in diagnosis, biochemical investigation and monitoring of many alarming diseases. Medically important enzymes produced by microorganisms have advantage of being economically feasible and consistent. They have high yield and are easy for product modification and optimization. The present review compiles the information on the sources and application of medically important enzymes produced by microorganisms and future prospects of these enzymes as drugs. Introduction The enzyme technology is applied to Regular consumption of enzymes and pharmaceutical research, development and enzyme-rich foods contributes to vibrant manufacturing and is a growing field. health, prevention of disease, and anti- Therapeutic enzymes have been in use for ageing process. Each cell in our body needs around at least 40 years. For example, a enzymes for its biochemical functions, and a therapeutic enzyme was described as a part deficiency of these enzymes will accelerate of replacement therapies for genetic the aging process. Some of the important deficiencies in 1960s by de Duve (Vellard, functions of enzymes are regulation of the 2013). Attempts are made to capitalize on growth of the body from a single cell to a the advantages of enzymes as drugs at every mature organism, conversion of food to pharmaceutical research center in the world energy to fulfill the body s needs, and break (Gonzalez and Isaacs, 1999). down or buildup of certain substances within the cell (Kaur and Sekhon, 2012). 17 Int.J.Curr.Microbiol.App.Sci (2015) 4(4): 17-26 Enzymes were largely ignored as drugs ready purification. Medically important other than digestion aids. In the later years enzymes are usually marketed as lyophilized of 19th century, crude proteolytic enzymes pure preparations with biocompatible were used to treat gastrointestinal disorders buffering salts and mannitol diluent. The only e.g. pepsin for dyspepsia. Later, cost of these enzymes is high but do not researchers observed that an extra cellular exceed or are comparable to those of secretion i.e. nuclease (enzymatically therapeutic agents or treatments (Gurung et degrades nucleic acid) of Bacillus al., 2013). pyocyaneus kills anthrax bacilli and protects mice from otherwise lethal bacterial Different types of therapeutic enzymes inoculum. This became a milestone in the use of parental enzyme in the treatment of Medically important enzymes (digestive and infections, cancers and finally diverse metabolic) can be used either alone or in spectrum of diseases. Supplements of combination with other therapies for treating enzymes are available in pills, capsules and a variety of diseases safely. These enzymes powder form and often consist of a have two important features, a) they often combination of different enzymes (Gonzalez bind and act on their targets with a high and Isaacs, 1999). Enzymes have chiral affinity and specificity; b) they have selectivity property which is employed to catalytic property and convert multiple prepare enantiomerically pure target molecules to the desired products. pharmaceuticals (Underkofler et al., 1957). These two features are exploited to make enzymes specific and potent drugs for a Majority of medically important enzymes numerous disorders (Cooney and are obtained from a limited number of fungi, Rosenbluth, 1975). yeast and bacteria. These organisms are also considered when a new enzyme is required Medically important enzymes produced by (Teal and Wymer, 1991). Medically microorganisms find their application in important enzymes are required in very less removal of cytotoxic substances within the quantity as compared to the industrially blood circulation, treatment of life important enzymes. But they should have a threatening disorders as oncolytics, high degree of purity and specificity. The thrombolytics, anti-coagulants and as replacements for metabolic deficiencies (Kaur and Sekhon, 2012). There is very less kinetics of these enzymes are low and information about the utilization of microbial enzymes for therapeutic purposes except for some anticancer enzymes and the enzymes active against cystic fibrosis (Sabu, 2003). high max, therefore it has maximum There major application is in the treatment of cancer (prodrug activator enzymes and efficiency even at low concentrations of antineoplastic enzymes) and various other enzymes and substrates. The sources of diseases as genetic diseases including these kinds of enzymes should be selected Gaucher, Fabry, MPS I, Pompe, MPS VI, with great care and precautions to prevent SCID, CF and PKU & infectious diseases any possibility of undesirable contamination caused by protozoa, fungi or bacteria. They by incompatible material and also to enable 18 Int.J.Curr.Microbiol.App.Sci (2015) 4(4): 17-26 can also be used to aid digestion where they individual s body s natural healing process are used to supplement lipase, protease and (Ostlie et al., 2012). amylase in lactose intolerant people who require lactose as their body is unable to Lipase is used as digestive aids. It is also produce it. used in the treatment of malignant tumors as they have the ability to activate tumor Asparginase is employed for the treatment necrosis factor. Lipases were used in the of acute lymphocytic leukemia. Tumor cells treatment of dyspepsia, gastrointestinal lack aspartate-ammonia ligase activity, disturbances, cutaneous manifestations of which stops the synthesis of nonessential digestive allergies, and many more such amino acid L-asparagine. The activity of infections in the past. Lipase from Candida asparginase is based on this fact. The rugosa synthesizes lovastatin, a drug that asparginase does not affect the normal cells has the ability to lower serum level of which have the capability to synthesize L- cholesterol. The hydrolysis of 3- asparagine for their own need, but they phenylglycidic acid ester, which is cause a decline in the free exogenous asymmetric, is a key intermediate in the concentration, which causes a state of fatal synthesis of diltiazem hydrochloride. It is a starvation in the tumor cells. The enzyme widely used coronary vasodilator and is can be administered intravenously and is synthesized using S. marcescens lipase effective only when the asparagine levels (Matsumae et al., 1993). within the bloodstream are extremely low (Gurung et al., 2013). Nattokinase is a serine proteinase obtained from Bacillus subtilis. It can reduce some Chitinase has antimicrobial property. Chitin factors of blood clotting and lipids that are is the component of cell wall of many associated with an increased risk for pathogenic organisms, including fungi, cardiovascular disease (CVD). Oral protozoa, and helminthes and is a good administration of nattokinase could be target for antimicrobials (Fusetti et al., considered as a CVD neutraceutical. It 2002). The cell walls of Streptococcus decreases the plasma levels of fibrinogen, pneumonia, Bacillus anthracis, and factor VII, and factor VIII (Hsia et al., Clostridium perfringens are targeted using 2009). Nattokinase shows prolonged action lytic enzyme derived from bacteriophage of preventing coagulation of blood and (Zimmer et al., 2002). These lytic enzymes dissolving existing thrombus (Milner, 2008). derived from bacteriophages can be used for the treatment of several infections and also Serratiopeptidase is useful in the treatment shows activity against new drug-resistant of pain and inflammation. It has three bacterial strains. Proteolytic enzymes have mechanisms to reduce inflammation. It anti-inflammatory actions. Huge number of breaks down fibrin, the insoluble protein these proteolytic enzymes of bacterial origin byproducts of blood coagulation and thins can also be employed in the removal of dead the fluids formed from inflammation and skin of burns (Gurung et al., 2013). injury. It also facilitates their drainage which increases the speed of the tissue repair Collagenase helps in the healing of burns process. It also alleviates pain as it inhibits and skin ulcers. It helps to break up and the release of bradykinin, a specific pain remove dead skin and tissue and thus help in inducing peptide (Rothschild, 1991; Esch repair mechanism. This in turn helps and Fabian, 1989). antibiotics to work better and speed up an 19 Int.J.Curr.Microbiol.App.Sci (2015) 4(4): 17-26 Thrombolytic drugs (Fibrinolytics) are created a great