Detection and Expression of Biosynthetic Genes in Actinobacteria ...

BERVANAKIS, G.Chapter 1: INTRODUCTIONSection 3: Secondary Metabolites Produced byActinobacteriaThe focus of this study is concerned with the molecular screening of polyketide, β-lactam and aminoglycoside deoxysugar biosynthetic pathway genes in a group ofenvironmental actinobacterial isolates. A characteristic feature shared by secondarymetabolites (SMs) derived from these pathways is that they are synthesized bycommon early biosynthetic steps. In the following paragraphs details will bepresented on each of these pathways and their respective genes controlling thesepathways and the secondary metabolite biosynthetic genes (SMBGs) that wereselected to be incorporated in this study.1.3.1 General Aspects of PolyketidesPolyketides are a ubiquitous class of SMs that are commonly produced byactinobacteria (Table 3). The economic importance of this class of compounds in thecase of the anthracycline, doxorubicin (Adriamycin) used as a antitumor drug alonewas $156 million in the year 1993 (Strohl, 1997). The polyketides are composed oftwo classes found in actinobacteria. These include the aliphatic (Type I) and aromatic(Type II) polyketides. The type I polyketides, which include macrolides andpolyethers, are synthesized by polyketide synthase modules that consist of severaldomains with defined functions responsible for the catalysis of one cycle ofpolyketide chain elongation (Figure 6). These type I polyketides are built from a widerange of simple carbon building blocks (acetates, propionates etc) and are extensivelyreduced. The type II polyketides which include anthracyclines andisochromanequinones are synthesized by polyketide synthases that catalyze sequentialdecarboxylative condensation between the starter and extender units to yield a linearpoly-β-ketone intermediate (Figure 8B) This intermediate undergoes reduction,aromatization or cyclization to form polycyclic aromatic structures which are furthermodified by tailoring enzymes which are responsible for the various biologicalactivities (Katz & Donadio, 1993; Khosla & Zawada, 1996)._____________________________________________________________________11