Genes for biosynthesis of butenolide-like signalling molecules in Streptomyces ghanaensis, their role in moenomycin production

Abstract

Moenomycins (Mm) – phosphoglycolipid compounds produced by Streptomyces ghanaensis ATCC14672 – are considered a promising model for development of novel class of antibiotics. In this regard it is important to generate Mm overproducing strains which would be a basis for economically justified production of this antibiotic. In this work a set of genes for synthesis and reception of low-molecular weight signaling molecules (LSM) in ATCC14672 were described and their significance for Mm production was studied. The ATCC14672 genome carries structural and regulatory genes for production of LSMs of avenolide and γ-butyrolactone families. Additional copies of LSM biosynthetic genes ssfg_07848 and ssfg_07725 did not alter the Mm production level. ATCC14672 LSMs are not capable of restoring the sporulation of butyrolactone-nonproducing mutant of S. griseus. Likewise, while the heterologous host S. lividans 1326 produced Mm, its mutant M707 (deficient in the butyrolactone synthase gene scbA) did not. Thus, while the natural level of LSMs production by ATCC14672 does not limit Mm synthesis, the former is essential for the synthesis of moenomycins.

Genetic Engineering of Streptomyces ghanaensis ATCC14672 for Improved Production of Moenomycins

“…Several studies have been undertaken to explore the regulation of Mm biosynthesis. Interestingly, regulatory genes are not present in the moe cluster and numerous global regulators were shown to influence Mm production [16][17][18][19][20][21][22][23][24][25][26]. A central role in the regulation of Mm biosynthesis belongs to the pleiotropic regulator AdpA gh , which was shown to directly activate the transcription of moe genes [19].…”