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

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.

保罗霉素是一类糖基化化合物，具有独特的保罗酸部分。为了定位它们的生物合成基因簇，对两种保罗霉素产生菌——保罗链霉菌NRRL 8115和链霉菌YN86的基因组进行了测序。通过对这两个基因组以及第三种保罗霉素产生菌白色链霉菌J1074的基因组进行比较分析，确定了保罗霉素生物合成基因簇。随后，通过使保罗链霉菌NRRL 8115中参与保罗糖分支链（pau11）和A环部分（pau18）生物合成的两个基因失活，证实了保罗霉素生物合成基因簇的身份。在确定了基因簇边界之后，基于pau基因的推导功能，提出了保罗霉素的汇聚式生物合成模型。最后，通过在保罗链霉菌中表达一个激活剂编码基因（pau13）构建了一株保罗霉素高产菌株，为未来的研究奠定了基础。