Scale-up fermentation of echinocandin type antibiotic FR901379.
Industrial-scale production of FR901379 (WF11899A), which is a novel echinocandin type of lipopeptide antibiotic produced by mutant strain M-7 from Coleophoma empetri F-11899 (FERM BP-2635), was demonstrated. In order to achieve high-level production in fermentor culture, the medium previously developed was modified, in which three types of organic nitrogen were replaced by ammonium sulfate and corn steep liquor. To eliminate increase in viscosity, carbon source was intermittently fed. The viscosity was reduced from 20,000 cP to less than 10,000 cP. The FULLZONE impeller was introduced in the fermentor culture for sufficient mixing. Mixing time was quite improved and high reproducibility was achieved. Surprisingly, the viscosity of the broth was reduced to 1000 cP in a 4 m(3) scale fermentor. When k(L)a was selected as an index for scale-up and industrial scale production using a 15 m(3) fermentor with the FULLZONE impeller was conducted, FR901379 production was successfully obtained at more than 50 U/mL, almost the same level as with the 0.03 m(3) and 4 m(3) fermentors. In addition, superior reproducibility was obtained, and 500-fold scale-up was successfully achieved.
Kanda
Munekazu
M
Fermentation and Biotechnology Laboratories, Astellas Pharma Inc., 156 Nakagawara, Kiyosu, Aichi, Japan.
Yamamoto
Eiji
E
Hayashi
Akihiro
A
Yabutani
Tetsuya
T
Yamashita
Michio
M
Honda
Hiroyuki
H
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001203:Ascomycota / Q000254:growth & development / Q000378:metabolism; D019149:Bioreactors / Q000382:microbiology; D001709:Biotechnology / Q000379:methods*; D054714:Echinocandins / Q000096:biosynthesis / Q000737:chemistry; D005285:Fermentation; D055666:Lipopeptides / Q000096:biosynthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry; D014783:Viscosity
D000900:Anti-Bacterial Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; C090474:WF 11899A