Genome Engineering Approaches to Improve Nosokomycin A Production by Streptomyces ghanaensis B38.3

Abstract

Here we describe our efforts to improve the levels of phosphoglycolipid antibiotic nosokomycin A production by Streptomyces ghanaensis ATCC14672 via genome engineering approaches. Introduction of two extra copies of leucyl tRNA (UUA) gene bldA and one copy of moenomycin biosynthesis gene cluster led, on average, to threefold increase in nosokomycin A titers (up to 1.5 mg/ L). Our results validate genome engineering approach as a viable strategy to improve moenomycin production.

Genetic Engineering of Streptomyces ghanaensis ATCC14672 for Improved Production of Moenomycins

“…ghanaensis is one of few streptomycetes known for the ability to produce Mm. Many studies have been conducted in order to improve low Mm production levels, including utilization of heterologous hosts for the expression of moe genes [14,16,17,19,23]. However, none of the tested hosts were superior over the wild-type strain in terms of Mm productivity.…”

“…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].…”