Process Of Fermentation And Purification Of Lovastatin

Lovastatin as an inhibitor of HMG-CoA reductase from microorganisms, has been a potent cholesterol-lowering drug. It was found that Aspergillus terreus, Penicillium citrinum and Monascus rubber could produce lovastatin, in which Aspergillus terreus is generally applied in industrial production.A strain (Aspergillus terreus) named SIPI-L-H525 was used in this study. After natural separation, it was inoculated into seed medium. The seed culture was diluted and dealed with by supersonic quassation, then mutated by ultraviolet mutation.Through the preliminary screening and secondary screening, we got a high-producing strain named SIPI-L-U512. Also we determined the HPLC analysis method of lovastatin.Improving the composition of the fermentation medium in shake flasks by single factor experiments was carried out. The result showed that maltodextrin was the best carbon source, soybean powder and corn steep powder were the best nitrogen sources. Many conditions of lovastatin fermentation were investigated including culture volume, inoculation ratio, initial pH of fermentation medium, cultural temperature. And more addition of precursor was also investigated. The results showed that addition 100ml medium in a 750ml shake flask was suitable, the best inoculation ratio was 14%, the best initial pH of fermentation medium was 6.5, suitable cultural temperature was 28℃.On the other hand, feeding 0.75% tri-sodium citrate into the broth at Oh of cultivation increased the fermentation potency and reached 9134.0mg/L. Compared to that of basal condition without any addition of precursor, the productivity was increased by 26.8%.It was studied that the process of isolation and purification of lovastatin from the broth. At first, the broth was acidified, then centrifuged to get mycelia, which was heated and powdered; finally we use acetic ether to soak the powder. After that, the phase of acetic ether was washed using the solution of ammonium sulfate and the solution of ethanedioic acid, then concentrated to gain pulps. It was crystallized at 4℃.The coarse crystals was decolorized by activated carbons, the pure needle crystal of lovastatin was obtained.