A novel enzyme conferring streptothricin resistance alters the toxicity of streptothricin D from broad-spectrum to bacteria-specific.

The Journal of Biological Chemistry
Yoshimitsu HamanoHiroshi Takagi

Abstract

Streptothricins (STs) produced by Streptomyces strains are broad-spectrum antibiotics. All STs consist of a carbamoylated D-gulosamine to which the beta-lysine homopolymer (1 to 7 residues) and the amide form of the unusual amino acid streptolidine (streptolidine lactam) are attached. Although many ST-resistance genes have been identified in bacteria, including clinically isolated pathogens and ST-producing Streptomyces strains, only one resistance mechanism has been identified to date. This mechanism involves the modification of the ST molecule by monoacetylation of the moiety of the beta-lysine(s). In this study, we successfully isolated a novel ST-resistance gene (sttH) from Streptomyces albulus, which is a known ST nonproducer. The in vitro analysis of SttH demonstrated that this enzyme catalyzes the hydrolysis of the amide bond of streptolidine lactam, thereby conferring ST resistance. Interestingly, the selective toxicity of ST-D possessing 3x beta-lysine moiety was altered from broad-spectrum to bacteria-specific by the hydrolysis of streptolidine lactam, although ST-F (1 x beta-lysine) was detoxified by SttH in both prokaryotes and eukaryotes (yeasts). STs have not been clinically developed due to their toxicities; howe...Continue Reading

References

Jan 1, 1991·Methods in Enzymology·F Sherman
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Oct 1, 1971·The Journal of Antibiotics·H TaniyamaT Kitagawa
Oct 1, 1980·Chemical & Pharmaceutical Bulletin·T TakemotoH Taniyama
Nov 26, 1997·Journal of Bacteriology·M A Fernández-MorenoF Malpartida
Jun 22, 2000·Journal of Molecular Biology·L A KelleyM J Sternberg
Jul 15, 2003·Clinical Microbiology Reviews·Sergei B Vakulenko, Shahriar Mobashery
Apr 13, 2004·Eukaryotic Cell·Alexander IdnurmJoseph Heitman
Feb 1, 2005·The Journal of Antimicrobial Chemotherapy·Gisele PeiranoDalia dos Prazeres Rodrigues
Aug 6, 2005·Journal of Clinical Microbiology·Sally R Partridge, Ruth M Hall
Oct 4, 2005·Protein Science : a Publication of the Protein Society·Jonathan CaruthersEthan A Merritt
Sep 1, 1943·Journal of Bacteriology·S A Waksman
Jan 1, 2006·CSH Protocols·Joseph Sambrook, David W Russell

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Citations

Apr 1, 1990·Chemistry and Physics of Lipids·D B Fenske, R J Cushley
Feb 1, 1990·Chemistry and Physics of Lipids·M Vauhkonen, P Somerharju
Feb 16, 2008·The Journal of Antibiotics·Zhiqin JiWenjun Wu
Mar 21, 2009·The Journal of Antibiotics·Zhiqin JiWenjun Wu
Jul 24, 2012·Nature Chemical Biology·Chitose MaruyamaYoshimitsu Hamano
Nov 10, 2009·Bioscience, Biotechnology, and Biochemistry·Chitose Maruyama, Yoshimitsu Hamano
Mar 13, 2018·Environmental Microbiology·Serina L RobinsonLawrence P Wackett
Mar 5, 2015·Chemical Society Reviews·Sherif I ElshahawiJon S Thorson
Aug 27, 2017·Applied and Environmental Microbiology·Rachel M Burckhardt, Jorge C Escalante-Semerena
Jul 3, 2013·Natural Product Reports·Yoshimitsu HamanoKuniki Kino
Feb 13, 2018·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Kohei UematsuHajime Katano

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