Evolution of the clusters of genes for -lactam antibiotics: a model for evolutive combinatorial assembly of new -lactams

β-Lactam antibiotics are produced by prokaryotic and eukaryotic organisms. The genes for β-lactam biosynthesis are organized in clusters but the location of the different genes is not identical. Biosynthesis genes are clustered with genes for resistance ( bla , pbp ) and for the efflux of the antibiotic ( cmc T) in prokaryotes. Comparison of proteins reveals much larger differences for primary metabolism enzymes than for β-lactam biosynthesis enzymes in producing organisms. This suggests a horizontal transfer of the β-lactam antibiotic biosynthesis genes.