An in-cluster Sfp-type phosphopantetheinyl transferase instead of the holo-ACP synthase activates the granaticin biosynthesis under natural physiological conditions

When cultivated on ISP2 plates for sporulation, the gra-orf32 deletion mutant of Streptomyces vietnamensis produced much more granaticins than in liquid or on solid YEME. The transcriptome analysis showed that the transcription levels of more than 1,600 genes were significantly changed (p < 0.05, log2 fold change >1). Amongst them, 872 genes were upregulated and 762 genes were downregulated on ISP2 plates, compared to those on YEME plates. KEGG pathway enrichment analysis showed that four pathways were enriched significantly, including two type II PKS biosynthesis pathways, namely, the granaticin biosynthetic pathway and the kinamycin-like biosynthetic pathway. These results suggested that the kinamycin-like biosynthetic pathway was activated on ISP2 plates and might associate with the elevated production of granaticins. Most of the PPTase genes kept in low-levels of expression or inactivated, even the expression level of the FAS ACPS gene (SVTN_RS23020) was not as high as expected. Two PPTase genes, SVTN_RS03505 and SVTN_RS28640 were slightly upregulated on ISP2 plate, while the FAS ACPS gene (SVTN_RS23020) was downregulated, compared to those on YEME plates. Overall design: Comparative gene expression profiling analysis of RNA-seq data for the gra-orf32 deletion mutant of Streptomyces vietnamensis cultivated on ISP2 and YEME plates for 24 h.