US2003138841A1PendingUtilityA1

Library of novel ''unnatural'' natural products

47
Priority: Apr 30, 1998Filed: Apr 22, 2002Published: Jul 24, 2003
Est. expiryApr 30, 2018(expired)· nominal 20-yr term from priority
Inventors:Robert Mcdaniel
A61P 29/00A61P 31/00C07H 17/08C07D 313/00C12N 15/52C40B 40/00C07K 2319/00C12N 9/1029A61P 1/00
47
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Claims

Abstract

Genetic engineering of the erythromycin polyketide synthase genes to effect combinatorial alterations of catalytic activities in the biosynthetic pathway can be used to generate a library of macrolides impractical to produce by chemical methods. The library includes examples of analogs with one, two and three altered carbon centers of the polyketide products.

Claims

exact text as granted — not AI-modified
We claim:  
     
         1 . A library of polyketides composed of the polyketide compounds shown in FIG. 2.  
     
     
         2 . A library of recombinant polyketide synthase (PKS) genes comprising the genes encoding the polyketides of  claim 1 .  
     
     
         3 . A library of host cells containing the genes of  claim 2 .  
     
     
         4 . A library of polyketides composed of the polyketides produced by contacting the polyketides of  claim 1  with a host cell selected from the group consisting of  Saccharopolyspora erythraea, Streptomyces venezuelae, S. narbonensis, S. antibioticus, S. fradiae, S. thermotolerans,  and  Micromonospora megalomicea.    
     
     
         5 . The library of  claim 4 , wherein said host cell is  Saccharopolyspora erythraea.    
     
     
         6 . The library of  claim 4 , wherein said host cell is  Streptomyces venezuelae.    
     
     
         7 . The library of  claim 4 , wherein said host cell is  S. narbonensis.    
     
     
         8 . The library of  claim 4 , wherein said host cell is  S. fradiae.    
     
     
         9 . The library of  claim 4 , wherein said host cell is  S. thermotolerans.    
     
     
         10 . The library of  claim 4 , wherein said host cell is  Micromonospora megalomicea.    
     
     
         11 . The library of  claim 4 , wherein said host cell is  S. antibioticus.    
     
     
         12 . The library of  claim 5 , wherein said polyketides comprise a C-6 hydroxyl group.  
     
     
         13 . The library of  claim 12 , wherein said polyketides comprise a C-6 hydroxyl group but lack a C-12 hydroxyl group.  
     
     
         14 . The library of  claim 13 , wherein said polyketides have been treated with mild acid to form a hemiketal.  
     
     
         15 . A polyketide in the library of  claim 14  in substantially pure form.  
     
     
         16 . The polyketide that is 6-deoxy-12-norerythronolide B.

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