Fermentation studies of rustmicin production by a Micromonospora sp.
The antifungal antibiotic rustmicin was detected in the fermentation broth of the actinomycete MA 7094 as a specific inhibitor of sphingolipid biosynthesis in Candida albicans and as a potent fungicidal agent against Cryptococcus neoformans. Taxonomic characterization by both classical means and PCR fingerprinting supported the assignment of the producing culture to the genus Micromonospora. Fermentation medium optimization studies showed that the concentration of tomato paste in the medium was critical to increased production of rustmicin by MA 7094. The stimulatory effect of tomato paste in the medium on rustmicin production appeared to be related to the maintenance of pH at or below a value of 6.0. Addition of the antifoam agent P-2000 to the fermentation was found to dramatically reduce the rustmicin titer, while substitution of another antifoam agent, UCON-LB625, resulted in a 100% increase in the amount of rustmicin detected. After fermentation optimization studies and the generation of a non-sporulating mutant of MA 7094, the rustmicin titer was increased from an initial titer of 10mg/liter to 145 mg/liter.
Sigmund
J M
JM
Department of Natural Products Drug Discovery, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Hirsch
C F
CF
D000934:Antifoaming Agents / Q000494:pharmacology; D000935:Antifungal Agents / Q000378:metabolism*; D003470:Culture Media; D016172:DNA Fingerprinting; D005285:Fermentation / Q000187:drug effects / Q000528:radiation effects; D007783:Lactones / Q000378:metabolism; D008847:Micromonospora / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D016296:Mutagenesis / Q000528:radiation effects; D016133:Polymerase Chain Reaction; D014466:Ultraviolet Rays
D000934:Antifoaming Agents; D000935:Antifungal Agents; D003470:Culture Media; D007783:Lactones; C047784:rustmicin