Sigmund J M, Hirsch C F
Department of Natural Products Drug Discovery, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
J Antibiot (Tokyo). 1998 Sep;51(9):829-36. doi: 10.7164/antibiotics.51.829.
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.
在放线菌MA 7094的发酵液中检测到抗真菌抗生素锈霉素，它是白色念珠菌鞘脂生物合成的特异性抑制剂，也是新型隐球菌的强效杀菌剂。通过经典方法和PCR指纹图谱进行的分类学鉴定支持将产生菌归为小单孢菌属。发酵培养基优化研究表明，培养基中番茄酱的浓度对于MA 7094提高锈霉素产量至关重要。培养基中番茄酱对锈霉素生产的刺激作用似乎与将pH维持在6.0或更低的值有关。发现向发酵中添加消泡剂P-2000会显著降低锈霉素效价，而用另一种消泡剂UCON-LB625替代则使检测到的锈霉素量增加了100%。经过发酵优化研究并产生MA 7094的非产孢突变体后，锈霉素效价从最初的10毫克/升提高到了145毫克/升。
