Genetic and functional analysis of genes required for the post-modification of the polyketide antibiotic TA of Myxococcus xanthus

The antibiotic TA of Myxococcus xanthus is a complex macrocyclic polyketide , produced through successive condensations of acetate by a type I PKS (pol yketide synthase) mechanism, The genes encoding TA biosynthesis are cluster ed on a 36 kb DNA fragment, which has been cloned and analysed, The chemica l structure of TA and the mechanism by which it is synthesized indicate the need for several post-modification steps, which are introduced into the ca rbon chain of the polyketide to form the final bioactive molecule. These in clude the addition of several carbon atoms originating from acetate carbony l, three C-methylations, O-methylation and a specific hydroxylation. This p aper reports the analysis of five genes which are involved in the post-modi fication of TA, Their functional analysis, by specific gene disruption, sug gests that they may be essential for the production of the active antibioti c. The characteristics and organization of the genes suggest that they may be involved in the addition of the carbon atoms which arise from acetate.