Tiacumicin Production

Abstract

Methods, processes and materials for the production and recovery of Tiacumicins produced by culturing a microorganism belonging to the species Dactylosporangium aurantiacum subspecies hamdenensis having the ability to produce and accumulate one or more Tiacumicin in a nutrient medium comprising a carbon source, a nitrogen source, trace elements such as inorganic salts, and an adsorbent, wherein said nitrogen source comprises fish powder, and wherein said Tiacumicin is produced in a yield greater than about 50 mg/L broth.

1 . A process of producing Tiacumicin B that comprises culturing a microorganism having the ability to produce Tiacumicin B in a nutrient medium and accumulating at least one Tiacumicin B in the nutrient medium, wherein the yield of at least one Tiacumicin B is greater than about 50 mg/L of whole fermentation broth. 
     
     
         2 . A process according to  claim 1  wherein said yield is greater than about 100 mg/L broth. 
     
     
         3 . (canceled) 
     
     
         4 . A process according to  claim 1  wherein said yield is from about 50 mg/L broth to about 500 mg/L broth. 
     
     
         5 . (canceled) 
     
     
         6 . A process according to  claim 1  wherein said microorganism is  Dactylosporangium aurantiacum  NRRL 18085. 
     
     
         7 . (canceled) 
     
     
         8 . A process according to  claim 1  wherein said Tiacumicin B is isolated from said nutrient medium using techniques selected from the group consisting of: sieving and removing undesired material by eluting with at least one solvent or a solvent mixture; extraction with at least one solvent or a solvent mixture; Crystallization; chromatographic separation; High-Performance Liquid Chromatography (HPLC); MPLC; trituration; and extraction with saturated brine with at least one solvent or a solvent mixture. 
     
     
         9 . A process according to  claim 1  wherein said microorganism is cultured at a temperature from about 25° to about 35° C. and at a pH from about 6.0 to about 8.0. 
     
     
         10 . A process according to  claim 1  wherein the nutrient medium comprises one or more carbon sources selected from the group consisting of glucose, sucrose, starch, molasses, dextrins, whey, glycerol, lipids and corn meal. 
     
     
         11 . A process according to  claim 1  wherein the nutrient medium is fed with an additional carbon source as needed. 
     
     
         12 . A process according to  claim 1  wherein the nutrient medium comprises one or more nitrogen/organic sources capable of supporting microorganism growth selected from the group consisting of beef extract, soybean meal, whole yeast, yeast extract, soybean flour, peptone, casamino acid, fish powder, corn steep liquor, ammonium salts, casein and amino acids. 
     
     
         13 . A process according to  claim 12  wherein the nutrient medium comprises fish powder. 
     
     
         14 . A process according to  claim 1  wherein the nutrient medium comprises one or more inorganic salts capable of supporting microorganism growth selected from the group consisting of K 2 HPO 4 , MgSO 4 .7H 2 O and CaCO 3 . 
     
     
         15 . A process according to  claim 1  wherein the nutrient medium comprises at least one adsorbent capable of adsorbing one or more Tiacumicin B during said culturing wherein said adsorbent is selected from the group consisting of Amberlite XAD16, XAD16HP, XAD2, XAD7HP, XAD1180, XAD1600, IRC50, Duolite® XAD761 and a reverse phase silica gel. 
     
     
         16 . A process according to  claim 15 , wherein the reverse phase silica gel is selected from the group consisting of KP-C 18, KP-C 18-WP, and KP-C 18HS. 
     
     
         17 . A nutrient medium for the production of Tiacumicin B from a microorganism, said nutrient medium comprising a carbon source, a nitrogen source, trace elements, and an adsorbent, and wherein said nutrient medium is used to produce Tiacumicin B in a yield greater than about 50 mg/L broth. 
     
     
         18 . A nutrient medium according to  claim 17  wherein said Tiacumicin B yield is greater than about 100 mg/L broth. 
     
     
         19 . (canceled) 
     
     
         20 . A nutrient medium according to  claim 17  wherein said Tiacumicin B yield is from about 50 mg/L broth to about 500 mg/L broth. 
     
     
         21 . (canceled) 
     
     
         22 . A nutrient medium according to  claim 17  wherein said nitrogen source is fish powder. 
     
     
         23 . A nutrient medium according to  claim 17  wherein said microorganism is  Dactylosporangium aurantiacum  NRRL 18085. 
     
     
         24 . (canceled) 
     
     
         25 . A nutrient medium according to  claim 17  wherein the nutrient medium comprises at least one adsorbent capable of adsorbing Tiacumicin B during said culturing. 
     
     
         26 . A Tiacumicin B produced by culturing a microorganism belonging to the species  Dactylosporangium aurantiacum  subspecies  hamdenensis  having the ability to produce and accumulate Tiacumicin B in a nutrient medium comprising a carbon source, a nitrogen source, trace elements such as inorganic salts, and an adsorbent, wherein said nitrogen source comprises fish powder, and wherein said Tiacumicin B is produced in a yield greater than about 50 mg/L broth.