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.
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Acknowledgments
This publication was partially based on the research provided by the grant support of the State Fund for Fundamental Research (project no. F60/2-2015, to B.O.) and by NIH grants 2P01AI083214-04 and R03TW009424 (to S.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The usage of the Agilent 6520 Q-TOF spectrophotometer was made possible by the Taplin Funds for Discovery Program (P.I.: S.W.). We thank Santa Maria J. (Merck) for the careful reading and editing of the manuscript.
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Liliya Horbal and Bohdan Ostash equally contributed.
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Horbal, L., Ostash, B., Luzhetskyy, A. et al. A gene cluster for the biosynthesis of moenomycin family antibiotics in the genome of teicoplanin producer Actinoplanes teichomyceticus . Appl Microbiol Biotechnol 100, 7629–7638 (2016). https://doi.org/10.1007/s00253-016-7685-3
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DOI: https://doi.org/10.1007/s00253-016-7685-3