Patent
Process for the production of d-biotin
| العنوان: | Process for the production of d-biotin |
|---|---|
| Patent Number: | 5,922,581 |
| تاريخ النشر: | July 13, 1999 |
| Appl. No: | 08/833,411 |
| Application Filed: | April 04, 1997 |
| مستخلص: | A process for producing d-biotin comprises cultivating a microorganism of the genus Kurthia and which is resistant to biotin antimetabolites and capable of producing d-biotin in a medium under aerobic conditions, and separating the resulting d-biotin from the fermentation broth. The cultivation medium suitably contains an assimilable carbon source, a digestible nitrogen source, inorganic salts and other nutrients necessary for the growth of the microorganism at a pH of about 5-9, temperature of about 10-40.degree. C. and for a duration of about 1-10 days. The preferred microorganism are Kurthia sp. 538-KA26, 538-17H4, 538-51F9 and 538-2A 13 (DSM No. 10609, 10608, 10610 and 10607, respectively), which are also new, and as such represent a further aspect of the present invention. The so-produced d-biotin is one of the essential vitamins for the nutrition of animals, plants and microorganisms, and is important as a medicine or food additive. It is produced in particularly high yield by the process of the present invention. |
| Inventors: | Hoshino, Tatsuo (Kamakura, JPX); Noro, Akifumi (Fujisawa, JPX); Tazoe, Masaaki (Yokohama, JPX) |
| Assignees: | Roche Vitamins Inc. (Parsippany, NJ) |
| Claim: | We claim |
| Claim: | 1. An isolated microorganism which is a mutant of Kurthia sp. 538-6 (DSM No. 9454) and capable of fermentatively producing from about 40 mg/L to about 126 mg/L of d-biotin. |
| Claim: | 2. An isolated microorganism which is a mutant of Kurthia sp. 538-6 (DSM No. 9454), resistant to at least one biotin antimetabolite and capable of producing from about 4.0 mg/L to about 126 mg/L of d-biotin. |
| Claim: | 3. The microorganism according to claim 2 in which said antimetabolite is taken from the group consisting of acidomycin, 5-(2-thienyl)-valeric acid, .alpha.-methyl dethiobiotin, 2-methyl acidomycin, amiclenomycin and bisnorbiotinol. |
| Claim: | 4. The microorganism of claim 1 wherein said microorganism is Kurthia sp. 538-KA 26 (DSM No. 10609). |
| Claim: | 5. The microorganism of claim 1 wherein said microorganism is Kurthia sp. 538-17H4 (DSM No. 10608). |
| Claim: | 6. The microorganism of claim 1 wherein said microorganism is Kurthia sp. 538-51F9 (DSM No. 10610). |
| Claim: | 7. The microorganism of claim 1 wherein said microorganism is Kurthia sp. 538-2A 13 (DSM No. 10607). |
| Claim: | 8. A process for producing d-biotin which comprises |
| Claim: | (a) cultivating Kurthia sp. 538-2A13 having the identifying characteristics of DSM No. 10607 for about 24 hours at about 28.degree. C. in a culture media, said culture media comprising about 6% glycerol, about 5.5% proteose peptone, about 0.1% KH.sub.2 PO.sub.4, about 0.05% MgSO.sub.4 .multidot.7H.sub.2 O, about 0.05% FeSO.sub.4 .multidot.7H.sub.2 O, about 0.001% MnSO.sub.4 .multidot.5H.sub.2 O and about one drop of antifoam CA-115; |
| Claim: | (b) replenishing said culture media a sterile nutrient media, said nutrient media comprising about 40% glycerol and about 20% pepteose peptone; |
| Claim: | (c) cultivating said replenished culture media for about 120 hours at about 28.degree. C.; and |
| Claim: | (d) separating the resulting d-biotin from the culture media. |
| Claim: | 9. A process for producing d-biotin which comprises |
| Claim: | (a) cultivating a microorganism selected from the group consisting of Kurthia sp. 538-KA 26 (DSM No. 10609), Kurthia sp. 538-17H4 (DSM No. 10608), Kurthia sp. 538-51F9 (DSM No. 10610) and Kurthia sp. 538-2A13 (DSM No. 10607), said organism being resistant to at least one biotin antimetabolite and capable of producing d-biotin in a medium under aerobic conditions; and |
| Claim: | (b) separating the resulting d-biotin from the fermentation broth. |
| Claim: | 10. The process according to claim 9, wherein at least one biotin antimetabolite is selected from the group consisting of acidomycin, 5-(2-thienyl)-valeric acid, .alpha.-methyl dethiobiotin, 2-methyl acidomycin, amiclenomycin, and bisnorbniotinol or a mixture thereof. |
| Claim: | 11. The process according to claim 9, wherein the cultivation is carried out in a medium containing an assimilable carbon source, a digestible nitrogen source, inorganic salts, and other nutrients necessary for the growth of the microorganism at a pH value of about 5.0 to about 9.0, at a temperature of about 10.degree. C. to 40.degree. C., and for about 1 to 10 days under aerobic conditions. |
| Claim: | 12. The process according to claim 10, wherein the cultivation is carried out in a medium containing an assimilable carbon source, a digestible nitrogen source, inorganic salts, and other nutrients necessary for the growth of the microorganism at a pH value of about 5.0 to about 9.0, at a temperature of about 10.degree. C. to 40.degree. C., and for about 1 to 10 days under aerobic conditions. |
| Claim: | 13. The process according to claim 12, wherein the cultivation is carried out at a pH value of 6.5 to 7.5, at a temperature of 26.degree. C. to 30.degree. C., and for 48 to 96 hours under aerobic conditions and the carbon source is selected from the group consisting of glycerol and glucose. |
| Claim: | 14. The process according to claim 12, wherein the cultivation is carried out at a pH value of 6.5 to 7.5, at a temperature of 26.degree. C. to 30.degree. C., and for 48 to 96 hours under aerobic conditions and the nitrogen source is peptone. |
| Claim: | 15. The process according to claim 12, wherein the cultivation is carried out at a pH value of 6.5 to 7.5, at a temperature of 26.degree. C. to 30.degree. C., and for 48 to 96 hours under aerobic conditions and the inorganic salt is selected from the group consisting of monopotassium phosphate, magenesium sulfate, ferrous sulfate and manganese sulfate or combinations thereof. |
| Current U.S. Class: | 435/117; 435/119; 4352/521; 435/822 |
| Current International Class: | C12N 100; C12P 1710; C12P 1718 |
| Other References: | CAPLUS Abstract 1984:99663 -100:99663 Shaw et al., "The Vitamin requirements of Kurthia zopfil and Kurthia gibsonii" "Syst. Appl. Microbio." (1983) 4(4), pp. 439-443. Derwent Abstract No. AN-96-500371 (Abstract of JP 08 256 785A). Published Oct. 8, 1996. Agric. Biol. Chem., 47(5):1011-1016 (1983). Bergey's Manual of Systematic Bacteriology, 9th ed., vol. 2, p. 1255 (1984). Biochem. Biophys. Res. Comm., 18:788 (1965). J. Microbiological Methods, 6:237-245 (1987). Proc. Soc. Exp. Biol. Med., 56:95-98 (1944). |
| Primary Examiner: | Lilling, Herbert J. |
| Attorney, Agent or Firm: | Johnston, George W. Tramaloni, Dennis P. Ebel, Eileen M. |
| رقم الانضمام: | edspgr.05922581 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |