Methods for the production of biliverdin

Abstract

The present invention relates to compositions and methods for the production of biliverdin. In particular, the invention concerns methods for producing biliverdin in yeast, especially Candida albicans , and other microorganisms.

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . A biliverdin composition produced by the process of:
 (A) culturing a microorganism in the presence of a heme compound, wherein said microorganism possesses a heme oxygenase activity sufficient to convert heme into biliverdin; and   (B) recovering the produced biliverdin.   
     
     
         9 . The biliverdin composition of  claim 8 , wherein said microorganism substantially lacks a biliverdin reductase activity. 
     
     
         10 . The biliverdin composition of  claim 8 , wherein said microorganism has been modified to enhance said heme oxygenase activity. 
     
     
         11 . The biliverdin composition of  claim 8 , wherein said microorganism is selected from the group consisting of fungal and bacterial cells. 
     
     
         12 . The biliverdin composition of  claim 11 , wherein said microorganism is a  Candida  yeast. 
     
     
         13 . The biliverdin composition of  claim 12 , wherein said  Candida  yeast is  Candida albicans.    
     
     
         14 . The biliverdin composition of  claim 8 , wherein said produced biliverdin is α-biliverdin. 
     
     
         15 . A pharmaceutical composition comprising an amount of biliverdin sufficient to treat a disease or condition in a human or non-human mammal, or in tissue therefrom, wherein said disease or condition is selected from the group consisting of cancer, cardiovascular disease, inflammation and Alzheimer's disease, and wherein said biliverdin is produced by the process of:
 (A) culturing a microorganism in the presence of a heme compound, wherein said microorganism possesses a heme oxygenase activity sufficient to convert heme into biliverdin; and   (B) recovering the produced biliverdin.   
     
     
         16 . The method of  claim 15 , wherein said microorganism is selected from the group consisting of fungal and bacterial cells. 
     
     
         17 . The method of  claim 16 , wherein said microorganism is a  Candida  yeast. 
     
     
         18 . The method of  claim 17 , wherein said  Candida  yeast is  Candida albicans.    
     
     
         19 . The method of  claim 15 , wherein said produced biliverdin is α-biliverdin. 
     
     
         20 . A method of treating a human or non-human mammal for a disease or condition selected from the group consisting of cancer, cardiovascular disease, inflammation and Alzheimer's disease, wherein said method comprises administering to said human or non-human mammal a pharmaceutical composition comprising an amount of biliverdin sufficient to treat said disease or condition, wherein said biliverdin is produced by the process of:
 (A) culturing a microorganism in the presence of a heme compound, wherein said microorganism possesses a heme oxygenase activity sufficient to convert heme into biliverdin; and   (B) recovering the produced biliverdin.   
     
     
         21 . The method of  claim 20 , wherein said microorganism is selected from the group consisting of fungal and bacterial cells. 
     
     
         22 . The method of  claim 21 , wherein said microorganism is a  Candida  yeast. 
     
     
         23 . The method of  claim 22 , wherein said  Candida  yeast is  Candida albicans.    
     
     
         24 . The method of  claim 20 , wherein said produced biliverdin is α-biliverdin.