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The paulomycins are a group of glycosylated compounds featuring a unique paulic acid moiety. To locate their biosynthetic gene clusters, the genomes of two paulomycin producers,  Streptomyces paulus  NRRL 8115 and  Streptomyces sp . YN86, were sequenced. The paulomycin biosynthetic gene clusters were defined by comparative analyses of the two genomes together with the genome of the third paulomycin producer  Streptomyces albus  J1074. Subsequently, the identity of the paulomycin biosynthetic gene cluster was confirmed by inactivation of two genes involved in biosynthesis of the paulomycose branched chain ( pau11 ) and the ring A moiety ( pau18 ) in  Streptomyces paulus  NRRL 8115. After determining the gene cluster boundaries, a convergent biosynthetic model was proposed for paulomycin based on the deduced functions of the  pau  genes. Finally, a paulomycin high-producing strain was constructed by expressing an activator-encoding gene ( pau13 ) in  S .  paulus , setting the stage for future investigations.

Identification and Analysis of the Paulomycin Biosynthetic Gene Cluster and Titer Improvement of the Paulomycins in Streptomyces paulus NRRL 8115