Genome Sequencing and RNA Sequencing Analysis of Streptomyces hygroscopicus ATCC 29253 & Its Rapamycin-Hyperproducing Mutant

Rapamycin, also known as Sirolimus, is a macrolide produced by the bacteria Streptomyces hygroscopicus. It has immunosuppressant activity in humans and is used to prevent rejection in organ transplantation, especially useful in kidney transplant. Rapamycin and its derivatives, such as everolimus, are also used in a coronary stent coating. Lots of researches have been conducted about biosynthetic gene cluster and revealed genes encoding modular polyketide synthase(PKS), non-ribosomal peptide synthetase-like protein, and other biosynthetic genes.

In this study, we carried out the whole genome sequencing and RNA sequencing in order to compare the genes of the type strain, S. hygroscopicus ATCC 29253 with those of rapamycin-hyperproducing mutant.

From the whole genome sequencing, we found that 165 genes were changed in the mutant but only 23 genes among them given rise to the change of amino acid sequence because of codon degeneracy.

In other words, whole transcriptome analysis for the hyperproducing mutants showed that the genes involved in malonyl CoA-acyl carrier protein transacylase, alkyldihydroxyacetonephosphate synthase and hypothetical protein were up-regulated, but GCN5-related N-acetyltransferase, anti-sigma F factor antagonist(spoIIAA-2); anti sigma b factor antagonist RsbV and another hypothetical protein were down-regulated.