Detection and Expression of Biosynthetic Genes in Actinobacteria ...

BERVANAKIS, G.Chapter 1: INTRODUCTIONbeen used to increase SM yields, have included the use of sesame, groundnut andcoconut oil for anthracycline production (Arun & Dharmalingam, 1999).Table 12. Secondary metabolite synthases whose production is repressed by variouscarbon sources (Demain, 1989)Secondary Enzyme Repressing nutrient ActinobacteriaMetaboliteActinomycin Phenoxazinone synthaseTryptophan pyrrolaseGlucoseGlucose, glycerolStreptomyces antibioticusStreptomyces parvulusCephamycin Deacetoxycephalosporin Csynthetase (expandase)GlucoseNocardia lactamduransKanamycin N-AcetylkanamycinamidohydrolaseGlucose, mannose,fructose, maltose, lactoseStreptomyces kanamyceticusNeomycinPuromycinPhosphataseO-DemethylpuromycinO-methyltransferaseGlucoseGlucoseStreptomyces fradiaeStreptomyces albonigerStreptomycin MannosidostreptomycinaseStreptomyces griseusTetracyclineAnhydrotetracyclineoxygenaseGlucose, dextringalactose, mannoseGlucoseStreptomyces ambofaciens1.7.2.2.2 Nitrogen SourceOrganic nitrogen sources are often used in SM fermentations, as these compounds canbe broken down into smaller units that are transported into bacterial cells, e.g. aminoacids and ammonia (NH + 4 ). Ammonia (as the NH + 4 ion) is the preffered inorganicnitrogen source in actinobacterial SM fermentations, where it is added as ammoniumsulfate (NH 4 ) 2 SO 4 or ammonium chloride [NH 4 Cl] (Dunn, 1985).The presence of an excessive easily assimable nitrogen source exerts a repressiveeffect causing a decrease in the levels of secondary metabolites, mainly caused byammonium salts and amino acids (Ōmura & Tanaka, 1984). Repression is exerted onthe enzymes involved in SM biosynthesis. However, this can be alleviated by the useof complex nitrogen sources such as peptones or soybean meal (Bhattacharyya et al.,1998; Demain & Fang, 1995).1.7.2.2.3 Phosphate SourceA number of secondary metabolites produced by actinobacteria are known to beinfluenced by inorganic phosphate (PO 3- 4 ) regulation (Table 13). The mechanismsthat have been implicated in phosphate regulation include: (a) phosphate favoursprimary metabolism; a shift down in primary metabolism derepresses secondarymetabolism (Drew & Demain, 1977); (b) phosphate shifts carbohydrate catabolic_____________________________________________________________________39