Studies on the production of rosamicin by fermentation

Abstract

Rosamicin seems to be a promising macrolide drug in the near future because of its clinical \& medical efficacy and wide spectrum. Using the strain of $\mbox{\underline{Micromonospora}}$ $\mbox{\underline{rosaria}}$ NRRL 3718, a chemically defined medium was developed where the yield of rosamicin reached upto 230 μg/ml, and some process factors were also studied for the purpose of developing the process technology of rosamicin fermentation. The factors that were studied were : 1) Identification of fermentation product by T.L.C. 2) Selection of metal ions composition 3) Selection of carbon source and determination of its optimal concentration 4) Selection of nitrogen source and determination of its optimal concentration 5) Determination of optimal concentration of $CaCO_3$ 6) Determination of optimal concentration of phosphate 7) Effect of metal ions 8) Effect of temperature. The rosamicin compound was identified by T.L.C. technique and biological activity test of the developed spot. As a carbon source, soluble starch 4% was selected. As a nitrogen source, L-asparagine 0.15% was selected. The applicable concentrations of $CaCO_3$ & phosphate determined were 0.6% & 0.075%. Metal ions that were needed for the rosamicin production were $Mg^{2+}$, $Fe^{2+}$, $Cu^{2+}$, $Mn^{2+}$, $Zn^{2+}$, and among them, $Mg^{2+}$ and $Zn^{2+}$ played the most significant role. The minimum oxygen absorption rate that was to be supplied for the adequate production of rosamicin was about 40 mM $O_2/lㆍhrㆍatm$. In the study of the effect of fermentation temperature, it was found that rosamicin production happened better at the temperature range of 28-29℃ compared with that of 31-32℃ while the mycelial growth of the producing - organism happened better at the higher temperature range.