Novel aminoglycoside antibiotics, process for producing the same, and pharmaceutical use thereof

Abstract

The present invention relates to novel aminoglycoside antibiotics, a process for producing the same, and pharmaceutical use thereof. More specifically, the present invention relates to compounds represented by formula (I), a process for producing the same, and use of the same as antimicrobial agents. wherein R represents amino or hydroxyl.

1 - 23 . (canceled) 
     
     
         24 . A kanamycin producing strain of the genus  Streptomyces  capable of producing a compound represented by formula (I), 
       
         
           
           
               
               
           
         
         wherein 2-deoxy-scyllo-inosose synthase has been inactivated. 
       
     
     
         25 . The kanamycin producing strain according to  claim 24  which is 2-deoxystreptamine-dependent. 
     
     
         26 . The kanamycin producing strain according to  claim 24 ,
 wherein a gene that codes for a polypeptide selected from the following polypeptides (a) to (d) has been integrated:
 (a) a polypeptide consisting of an amino acid sequence represented by SEQ ID NO:1 having a mutation in which aspartic acid at position 136 has been changed to asparagine, 
 (b) a polypeptide consisting of the amino acid sequence defined in (a) in which one or more amino acids have been substituted, deleted, added, or inserted, the polypeptide having an activity functionally equivalent to the polypeptide defined in (a), and 
 (c) a polypeptide consisting of an amino acid sequence having 80% or more homology with the amino acid sequence defined in (a), the polypeptide having an activity functionally equivalent to the polypeptide defined in (a). 
   
     
     
         27 . The strain according to  claim 26 , wherein the polypeptide defined in (b) or (c) holds the mutation defined in (a). 
     
     
         28 . The strain according to  claim 26 , wherein the one or more amino acids in (b) is 1 to 40 amino acids. 
     
     
         29 . The strain according to  claim 26 , wherein the homology in (c) is not less than 90%. 
     
     
         30 . The strain according to  claim 24 , wherein the strain is  S. Kanamyceticus -DOS. 
     
     
         31 . The strain according to  claim 24 , capable of producing the compound represented by formula (I) in combination with a component selected from streptamine and myo-inositol. 
     
     
         32 . A composition comprising the kanamycin producing strain according to  claim 24  and a component selected from streptamine and myo-inositol. 
     
     
         33 . A composition comprising the kanamycin producing strain according to  claim 25  and a component selected from streptamine and myo-inositol. 
     
     
         34 . A composition comprising the kanamycin producing strain according to  claim 26  and a component selected from streptamine and myo-inositol. 
     
     
         35 . A composition comprising the kanamycin producing strain according to  claim 27  and a component selected from streptamine and myo-inositol. 
     
     
         36 . A composition comprising the kanamycin producing strain according to  claim 28  and a component selected from streptamine and myo-inositol. 
     
     
         37 . A composition comprising the kanamycin producing strain according to  claim 29  and a component selected from streptamine and myo-inositol. 
     
     
         38 . A composition comprising the kanamycin producing strain according to  claim 30  and a component selected from streptamine and myo-inositol. 
     
     
         39 . A composition comprising the kanamycin producing strain according to  claim 31  and a component selected from streptamine and myo-inositol. 
     
     
         40 . A method for treating or preventing an infectious disease, comprising administering an effective amount of a compound represented by formula (I) or its pharmacologically acceptable salt or their solvates to an animal including human: 
       
         
           
           
               
               
           
         
         wherein R represents amino or hydroxyl. 
       
     
     
         41 . The process according to  claim 40 , wherein the infectious disease is derived from  Staphylococcus aureus, Escherichia coli , or  Pseudomonas aeruginosa.