Open AccessAn unexpected role for the putative 4′‐phosphopantetheinyl transferase‐encoding gene nysF in the regulation of nystatin biosynthesis in Streptomyces noursei ATCC 11455
Author(s) -
Volokhan Olga,
Sletta Håvard,
Sekurova Olga N.,
Ellingsen Trond E.,
Zotchev Sergey B.
Publication year - 2005
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1016/j.femsle.2005.05.052
Subject(s) - gene cluster , biology , mutant , gene , genetics , reporter gene , promoter , acyl carrier protein , streptomyces albus , biosynthesis , streptomyces , biochemistry , gene expression , bacteria
The nysF gene encoding a putative 4′‐phosphopantetheinyl transferase (PPTase) is located at the 5′ border of the nystatin biosynthesis gene cluster in Streptomyces noursei . PPTases carry out post‐translational modification of the acyl carrier protein domains on the polyketide synthases (PKS) required for their full functionality, and hence NysF was assumed to be involved in similar modification of the nystatin PKS. At the same time, DNA sequence analysis of the genomic region adjacent to the nysF gene revealed a gene cluster for a putative lantibiotic biosynthesis. This finding created some uncertainty regarding which gene cluster nysF functionally belongs to. To resolve this ambiguity, nysF was inactivated by both insertion of a kanamycin (Km) resistance marker into its coding region, and by in‐frame deletion. Surprisingly, the nystatin production in both the nysF ::Km R and Δ nysF mutants increased by ca. 60% compared to the wild‐type, suggesting a negative role of nysF in the nystatin biosynthesis. The expression of xylE reporter gene under control of different promoters from the nystatin gene cluster in the Δ nysF mutant was studied. The data obtained clearly show enhanced expression of xylE from the promoters of several structural and regulatory genes in the Δ nysF mutant, implying that NysF negatively regulates the nystatin biosynthesis.