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.
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References
Ostash B, Walker S (2010) Moenomycin family antibiotics: chemical synthesis, biosynthesis, biological activity. Nat Prod Rep 27:1594–1617. https://doi.org/10.1039/c001461n
Sauvage E, Terrak M (2017) Glycosyltransferases and transpeptidases/penicillin-binding proteins: valuable targets for new antibacterials. Antibiotics 17:1–10. https://doi.org/10.3390/antibiotics5010012
Ostash B, Campbell J, Luzhetskyy A, Walker S (2013) MoeH5: a natural glycorandomizer from the moenomycin biosynthetic pathway. Mol Microbiol 90:1324–1338. https://doi.org/10.1111/mmi.12437
Lopatniuk M, Ostash B, Makitrynskyy R, Walker S, Luzhetskyy A, Fedorenko V (2015) Testing the utility of site-specific recombinases for manipulations of genome of moenomycin producer Streptomyces ghanaensis ATCC14672. J Appl Genet 56:547–550. https://doi.org/10.1007/s13353-015-0283-8
Gupta SK, Shukla P (2017) Gene editing for cell engineering: trends and applications. Crit Rev Biotechnol 37:672–684. https://doi.org/10.1080/07388551.2016.1214557
Makitrynskyy R, Ostash B, Tsypik O, Rebets Y, Doud E, Meredith T, Luzhetskyy A, Bechthold A, Walker S, Fedorenko V (2013) Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin. Open Biol 3:130121. https://doi.org/10.1098/rsob.130121
Ostash I, Kolvenbach B, Corvini PF, Fedorenko V, Ostash B, Cichocka D (2018) Gene cloning system for sulfonamide-mineralizing Microbacterium sp. strain BR1. J Appl Genet 59:119–121. https://doi.org/10.1007/s13353-017-0427-0
Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical Streptomyces genetics. John Innes Foundation, Norwich. ISBN 0-7084-0623-8
Ostash B, Makitrinskyy R, Walker S, Fedorenko V (2009) Identification and characterization of Streptomyces ghanaensis ATCC14672 integration sites for three actinophage-based plasmids. Plasmid 61:171–175. https://doi.org/10.1016/j.plasmid.2008.12.002
Agris PF, Narendran A, Sarachan K, Väre VYP, Eruysal E (2017) The importance of being modified: the role of RNA modifications in translational fidelity. Enzymes 41:1–50. https://doi.org/10.1016/bs.enz.2017.03.005
Acknowledgements
This work was supported by grants from the Ministry of Education and Science of Ukraine BG-46F and BG-41Nr (to V.F. and B.O., respectively).
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Kuzhyk, Y., Lopatniuk, M., Luzhetskyy, A. et al. Genome Engineering Approaches to Improve Nosokomycin A Production by Streptomyces ghanaensis B38.3. Indian J Microbiol 59, 109–111 (2019). https://doi.org/10.1007/s12088-018-0761-x
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DOI: https://doi.org/10.1007/s12088-018-0761-x