Detection and Expression of Biosynthetic Genes in Actinobacteria ...

BERVANAKIS, G.Chapter 1: INTRODUCTIONmetabolites branching-off into the pathway particular for a specific secondarymetabolite. Several primary metabolic pathways have been identified as sources ofprecursors for synthesis of secondary metabolites. These are: fatty acid metabolism(acetate and propionate for e.g. polyketide biosynthesis), carbohydrate metabolism(hexose, pyruvate), 4) the production of these secondary metabolites is regulated bypathway specific genes that determine the onset of secondary metabolite production(Hodgson, 2000).1.2.1.2 Functions of Secondary MetabolitesThe production of secondary metabolites serve a number of useful functionsbenefiting the organisms producing them. Firstly, they act as chemical agents indestroying other microorganisms and increase the fitness and the survival of theproducing organism in the natural environment (Demain, 1995a). Certain secondarymetabolites aid in metal transport providing metal ions in a soluble form which can bereadily utilised by microorganisms (Neilands, 1995). Other uses of secondarymetabolites include effectors of differentiation in sporulating bacteria (McCann &Pogell, 1979).1.2.1.3 Resistance Mechanisms and Secondary Metabolite SecretionThe degree of susceptibility to self-inhibition from secondary metabolites inactinobacteria is governed by the resistance mechanisms being elicited (Méndez &Salas, 2001). These mechanisms can either occur concurrently during idiophase ortriggered by sublethal levels of the SM. Secondary metabolite producingactinobacteria possess a range of defensive mechanisms which allows them to protectthemselves from their own metabolites. These mechanisms are described as follows;(a) enzymatic detoxification of the antibiotic (Figure 2; route 1), (b) alteration of theantibiotics normal target in the cell (Figure 2; route 2), and (c) modification of thepermeability to allow antibiotic to be pumped out of the cell and restrict its re-entry[Figure 2; route 3] (Cundliffe, 1989). (d) cytoplasmic proteins acts to sequester thesecondary metabolite (Sheldon et al., 1999; Wilson & Cundliffe, 1999), (e)suppressing antibiotic synthases during rapid growth (Vining, 1990). Other suicideavoidance mechanisms include the final biosynthetic step is located on the cellmembrane, production of the SM is during idiophase, feedback inhibition/repression.Resistance is tightly regulated with biosynthetic genes and this is evident from theirclose proximity to one another on chromosomal DNA (Figure 3)._____________________________________________________________________6