title: Identification of novel tylosin analogues generated by a wblA disruption mutant of Streptomyces ansochromogenes.
abstract: BACKGROUND
  Streptomyces, as the main source of antibiotics, has been intensively exploited for discovering new drug candidates to combat the evolving pathogens. Disruption of wblA, an actinobacteria-specific gene controlling major developmental transition, can cause the alteration of phenotype and morphology in many species of Streptomyces. One wblA homologue was found in Streptomyces ansochromogenes 7100 by using the Basic Local Alignment Search Tool. It is interesting to identify whether novel secondary metabolites could be produced by the wblA disruption mutant as evidenced in other Streptomyces.
  
  
  RESULTS
  The wblA disruption mutant of S. ansochromogenes 7100 (ΔwblA) was constructed by homologous recombination. ΔwblA failed to produce spores and nikkomycin, the major product of S. ansochromogenes 7100 (wild-type strain) during fermentation. Antibacterial activity against Staphylococcus aureus and Bacillus cereus was observed with fermentation broth of ΔwblA but not with that of the wild-type strain. To identify the antibacterial compounds, the two compounds (compound 1 and compound 2) produced by ΔwblA were characterized as 16-membered macrolides by mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical structure of these compounds shows similarity with tylosin, and the bioassays indicated that the two compounds inhibited the growth of a number of gram-positive bacteria. It is intriguing that they displayed much higher activity than tylosin against Streptococcus pneumoniae.
  
  
  CONCLUSIONS
  Two novel tylosin analogues (compound 1 and 2) were generated by ΔwblA. Bioassays showed that compound 1 and 2 displayed much higher activity than tylosin against Streptococcus pneumoniae, implying that these two compounds might be used to widen the application of tylosin.
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. Lucheng522@aliyun.com.|University of Chinese Academy of Sciences, Beijing, 100049, China. Lucheng522@aliyun.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China. guojianliao@gmail.com.
authors.forename: Guojian
authors.initials: G
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. zhang.jihui@im.ac.uk.
authors.forename: Jihui
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. tanhr@im.ac.cn.
authors.forename: Huarong
authors.initials: H
authors.lastname: Tan
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D052978:Disk Diffusion Antimicrobial Tests; D006027:Glycosides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D009154:Mutation; D010641:Phenotype; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015645:Tylosin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology
chemical_list: C000609247:23-O-mycinosyltylactone; C000609246:6-hydroxy-21-O-mycinosyltylactone; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006027:Glycosides; C011952:nikkomycin; D015645:Tylosin