title: A gene cluster for the biosynthesis of moenomycin family antibiotics in the genome of teicoplanin producer Actinoplanes teichomyceticus.
abstract: Moenomycins are phosphoglycolipid antibiotics notable for their extreme potency, unique mode of action, and proven record of use in animal nutrition without selection for resistant microflora. There is a keen interest in manipulation of structures of moenomycins in order to better understand their structure-activity relationships and to generate improved analogs. Only two almost identical moenomycin biosynthetic gene clusters are known, limiting our knowledge of the evolution of moenomycin pathways and our ability to genetically diversify them. Here, we report a novel gene cluster (tchm) that directs production of the phosphoglycolipid teichomycin in Actinoplanes teichomyceticus. Its overall genetic architecture is significantly different from that of the moenomycin biosynthesis (moe) gene clusters of Streptomyces ghanaensis and Streptomyces clavuligerus, featuring multiple gene rearrangements and two novel structural genes. Involvement of the tchm cluster in teichomycin biosynthesis was confirmed via heterologous co-expression of amidotransferase tchmH5 and moe genes. Our work sets the background for further engineering of moenomycins and for deeper inquiries into the evolution of this fascinating biosynthetic pathway.
authors.affiliation: Saarland University, Campus C2.3, 66123, Saarbrücken, Germany. lihorbal@gmail.com.|Ivan Franko National University of Lviv, Hrushevskoho 4, Lviv, 79005, Ukraine. lihorbal@gmail.com.
authors.forename: Liliya
authors.identifier: http://orcid.org/0000-0002-9541-7372
authors.initials: L
authors.lastname: Horbal
authors.affiliation: Ivan Franko National University of Lviv, Hrushevskoho 4, Lviv, 79005, Ukraine.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Ostash
authors.affiliation: Saarland University, Campus C2.3, 66123, Saarbrücken, Germany.|Helmholtz Institute for Pharmaceutical Research, 66123, Saarbrücken, Germany.
authors.forename: Andriy
authors.initials: A
authors.lastname: Luzhetskyy
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Blackfan Circle, Boston, MA, 02115, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
authors.affiliation: Technology Platform Genomics, CeBiTec, Bielefeld University, Universitätsstraße 25, 33615, Bielefeld, Germany.
authors.forename: Jorn
authors.initials: J
authors.lastname: Kalinowski
authors.affiliation: Ivan Franko National University of Lviv, Hrushevskoho 4, Lviv, 79005, Ukraine.
authors.forename: Victor
authors.initials: V
authors.lastname: Fedorenko
mesh_terms: D039903:Actinobacteria / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001455:Bambermycins / Q000096:biosynthesis*; D053898:Biosynthetic Pathways / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects; D005810:Multigene Family / Q000235:genetics*; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000235:genetics; D013329:Structure-Activity Relationship; D017334:Teicoplanin / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D009844:Oligosaccharides; D001455:Bambermycins; D017334:Teicoplanin; C419802:moenomycin
keywords: Actinoplanes; Moenomycins; Nosokomycin; Teichomycin