Antibiotics

One of the greatest achievements of medical science was the discovery of antibiotics which have profound importance on human health. Antibiotics are one of the best-known groups of the secondary metabolites synthesised by microorganisms, which are active against other microorganisms. Antibiotics affect a multitude of targets and essential cellular functions, which include DNA replication (actinomycin and griseofulvin), transcription (rifamycin), translation by 70S (S-Svedberg sedimentation mass value) ribosomes (chloramphenicol, tetracycline, erythromycin and streptomycin), transcription by 80S ribosomes (cyclohexamide), transcription by 70S and 80S ribosomes (puromycin and fusidic acid), cell wall synthesis (cycloserine, bacitracin, penicillin, cephalosporin and vancomycin) and cell membrane disruption (polymyxin and amphotericin, ionophores such as gramicidin, lonomycin and monensin) (Indu 2006).

Due to its enormous importance in human health care, demand for antibiotics is increasing worldwide. Moreover, continuous efforts are being made to decrease its production cost by process optimisation using raw materials like agricultural residues through different fermentation processes like SmF and SSF. Inexpensive substrates, such as agricultural residues and agro-industrial waste products have been found to be very valuable for economy and appropriate for biotechnological process. Their usage as substrate has widely opened the potential to reduce production costs up to 60 % by reducing the cost of raw material during fermentations (Lotfy 2007). The importance of agro-industrial residues in SSF system for the production of antibiotics and other secondary metabolites has gained much recognition in recent years (Mahalaxmi et al. 2010). Antibiotic production using SSF requires very minimum energy and less investment cost, and recently it has gained increased importance due to its higher productivity through fermentation, ecofriendliness and lesser disadvantages when compared to SmF (Poonam Singh and Pandey 2009).

Secondary Metabolites and Growth

Metabolites are organic compounds produced by organisms using multitude of enzyme-catalysed biochemical reactions called metabolic pathways. Metabolites can be the initial, the intermediary or the end products of these biochemical reactions. A variety of metabolites and reactions combine and work together allowing an organism to sustain life. Primary metabolites are found in almost all species within broad phylogenetic groups, produced by nearly the same pathway and are normally involved in growth, development and reproduction. The secondary metabolites are often restricted to a very narrow set of species within the same phylogenetic group. Secondary metabolites secreted by organisms are the chemical components that do not involve or interact in normal growth and development, but usually have a potent function. The growth and metabolism of many microorganisms in fermentation generally implies a series of phases. In microorganisms, secondary metabolites are not usually produced during the log or exponential phase of a culture (trophophase), but are synthesised in culture medium after a period of complete consumption of key nutrients, such as carbon, nitrogen, phosphate and mineral sources. Although primary and secondary metabolism share the common transcriptional and translational machinery, the nutrient depletion initiates the actions of precursors to accumulate products other than primary metabolites called the secondary metabolites during a subsequent production stage (idiophase).

Biosynthesis of Microbial Secondary Metabolites

The evolution of exciting and new secondary metabolic pathways is likely to have been driven by the ecological robustness, abiotic and biotic stresses and survival in unique ecosystem. Microbial secondary metabolites show enormous diversity of chemical structures. The biosynthetic pathways have emerged from network of primary metabolisms at a relatively small number of points (Barrios-Gonzalez et al. 2003) and evolve later independently.

Most secondary metabolites are synthesised from one or a combination of different biosynthetic pathways (Fig. 7.1):

1. Metabolites derived from sugars (streptomycin, neomycin and kanamycin)

2. Metabolites derived from shikimic acid pathway; shikimic acid is one of the major source for the biosynthesis of antibiotics (ansamycin and rifamycin)

3. Metabolites derived from aliphatic amino acid pathway for the biosynthesis of

β-lactam antibiotics (penicillin, cephalosporins and cephamycins)

4. Metabolites derived from chorismic acid pathway (candicidin, nystatin and

chloramphenicol)

5. Metabolites derived from aromatic amino acid pathway (actinomycin, indolmycin, novobiocin, lincomycin and polymyxin)

6. Metabolites derived from the acetyl-CoA and malonyl-CoA (erythromycin, vancomycin and tetracyclines)

Fig. 7.1 Metabolic pathways leading to biosynthesis of secondary metabolite, antibiotics

 
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