Prospects of engineering metabolites in microorganisms for therapeutics

Engineering metabolites in microorganisms are new tools for production of therapeutics. Microbial metabolic engineering involving manipulation of metabolic fluxes has helped in the production of novel antibiotics. The process of metabolic engineering and strategies adopted for over production of antibiotics, enzymes of therapeutical value and other therapeutic compounds are briefly described here. Bacteria, fungi and yeasts have been engineered for metabolites which are discussed with examples in this review. Globally the production of pharmaceuticals especially therapeutics has taken a new dimension through advanced computational tools by synthetic drug designing and biotechnological interventions like recombinant DNA technology. A variety of new drugs come into market with new innovations of research and development wings of pharmaceutical industry. Development of new antibiotics and vaccines has dramatically reduced the occurrences of diseases such as diphtheria, syphilis, and whooping cough which were threatening human over years. In addition, technology based on the study of genes is being explored to develop vaccines to prevent or treat diseases that have eluded traditional vaccines, such as AIDS, malaria, tuberculosis, and cervical cancer. In this context, new concept of engineering microbial metabolites has emerged as a boon to pharmaceutical industry. Metabolic engineering is the science that combines systematic analysis of metabolic and other pathways with molecular biological techniques to improve cellular properties by designing and implementing rational genetic modifications (Koffas et al., 1999). It draws principles from chemical engineering, computational sciences, biochemistry, molecular biology, analytical methods and mathematical tools for redirecting metabolic fluxes for industrial and medical purposes. This review focuses on the basic principles and concepts related to metabolic engineering in microorganisms and their applications for therapeutic production. Definitions of metabolic engineering Metabolic engineering has been defined in different ways by several eminent metabolic engineers but the ultimate crux is the manipulation of the metabolic flux in order to alter the cell physiology and cell behavior pattern for overproduction of metabolites. A few definitions of metabolic engineering are stated below.  Metabolic engineering has been defined as the targeted and purposeful alteration of metabolic pathways in an organism in order to better understand and utilize cellular pathways for chemical transformation, energy transduction, and supramolecular assembly (Lessard, 1996).  Neilsen (1998) has defined metabolic engineering as the purposeful modification of intermediary metabolism using recombinant DNA techniques.  Stephanopoulous (1999) has referred it as the direct improvement of cellular properties through the modification of specific biochemical reactions or introduction of new ones, with the use of recombinant DNA technology.