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|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.|
|Inventor(s):||Shue; Youe-Kong (Carlsbad, CA), Du; Chi-Jen Frank (Taipei, TW), Chiou; Ming-Hsi (Taoyuan, TW), Wu; Mei-Chiao (Taoyuan, TW), Chen; Yuan-Ting (Hualien, TW), Okumu; Franklin W. (San Diego, CA), Duffield; Jonathan James (San Diego, CA)|
|Assignee:||Optimer Pharmaceuticals, Inc. (San Diego, CA)|
|Filing Date:||Jul 15, 2003|
|Claims:||1. A process for producing tiacumicin B comprises: culturing a microorganism in a nutrient medium to accumulate the tiacumicin B in the nutrient medium; and isolating the tiacumicin B from the nutrient medium; wherein the nutrient medium comprises 0.5%-15% by weight of an adsorbent resin capable of absorbing the tiacumicin B. |
2. The process of claim 1 wherein the adsorbent resin is selected from the group consisting of Amberlite.RTM. XAD16, XAD16HP, XAD2, XAD7HP, XAD1180, XAD1600, IRC50, Duolite.RTM. XAD761 and a reverse phase silica gel.
3. The process of claim 1 wherein the microorganism is Dactylosporangium aurantiacum subspecies hamdenensis NHRL 18085.
4. The process of claim 1 wherein the isolating step is conducted by at least one of following methods: 1) sieving and removing undesired material by eluting with at least one solvent or a solvent mixture; 2) extraction with at least one solvent or a solvent mixture; 3) crystallization; 4) chromatographic separation; 5) High-Performance Liquid Chromatography (HPLC); 6) MPLC; 7) trituration; and 8) extraction with saturated brine with at least one solvent or a solvent mixture.
5. The process of claim 1 wherein the culturing step is conducted at a temperature from about 25 to about 35.degree. C. and at a pH from about 6 to about 8.
6. The process of 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.
7. The process of claim 1 wherein the nutrient medium is fed with an additional carbon source as needed.
8. The process of claim 1 wherein the nutrient medium comprises one or more inorganic salts selected from the group consisting of K.sub.2HPO.sub.4, MgSO.sub.4, 7H.sub.2O, and CaCO.sub.3.
9. The process of claim 1 wherein the nutrient medium comprises one or more nitrogen/organic sources 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.
10. The process of claim 2 wherein the reverse phase silica gel is selected from the group consisting of KP-C18, KP-C18-WP and KP-C18HS.