Critical Review of Biotransformational Studies on Steroids by Using Culture of Cunninghamella blakesleeana

: For several decades, biotransformational studies on steroidal compounds have gained a lot of attention because it is an efficient approach for the structural modification of complicated natural or synthetic compounds with high regio-, chemo- and stereoselectivity at environmentally friendly conditions. This review summarizes the use of different strains of Cunninghamella blakesleeana for the biotransformation of sixteen steroids 1-16 into a variety of transformed products. The transformed products may be important as a drug or precursor for the production of important pharmaceuticals. The types of reactions performed by C. blakesleeana include hydroxylation, epoxidation, reduction, demethylation, oxidation, glycosidation, double bond formation, side-chain degradation, isomerisation and opening of an isoxazol ring, which would be difficult to produce by traditional synthesis.

Lovastatin Production from Cunninghamella blakesleeana under Solid State Fermentation

Our earlier paper had established the fact that new soil fungi known as Cunninghamella blakesleeana is potent enough to produce lovastatin significantly. At present, there are no reports on the media optimization for the lovastatin production. Hence, the objective is to optimize the fermentation conditions for lovastatin production by Cunninghamella blakesleeana under Solid State fermentation (SSF) condition through screening the critical factors by one factor at a time and then, optimize the factors selected from screening using statistical approaches. SSF was carried using the pure culture of Cunninghamella blakesleeana KP780148.1 with wheat bran as substrate. Initial screening was performed for physical parameters, carbon sources and nitrogen sources and then optimized the selected parameters through PBD and BBD. Screening result indicated the optimum values of the analysed parameter for the maximal production of lovastatin by Cunninghamella blakesleeana were selected. Out of the nine factors MgSO4, (NH4)2SO4, pH and Incubation period were found to influence the lovastatin production significantly after PBD. The optimal levels of these variables and the effect of their mutual interactions on lovastatin production were determined using BBD surface design. The optimum medium composition was found to be MgSO4(0.2 g/L), (NH4)2 SO4 (12.5 g/L), pH (6) and Incubation period (7 days). Experimental studies showed a yield of 7.39 mg/g at the above optimized conditions which were observed to be very nearby to the predicted value and hence the model was successfully validated. Hence, this is the first report on the optimization of critical parameters for lovastatin production by Cunninghamella blakesleeana.

Evaluation of Microbial Transformation of 10-deoxoartemisinin by UPLC-ESI-Q-TOF-MSE

10-deoxoartemisinin is a semisynthetic derivative of artemisinin that lacks a lactone carbonyl group at the 10-position, and has stronger antimalarial properties than artemisinin. However, 10-deoxoartemisinin has limited utility as a therapeutic agent because of its low solubility and bioavailability. Hydroxylated 10-deoxoartemisinins are a series of properties-improved derivatives. Via microbial transformation, which can hydroxylate 10-deoxoartemisinin at multiple sites, the biotransformation products of 10-deoxoartemisinin have been investigated in this paper. Using ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MSE) combined with UNIFI software, products of microbial transformation of 10-deoxoartemisinin were rapidly and directly analyzed. The hydroxylation abilities of nine microorganisms were compared using this method. All of the microorganisms evaluated were able to hydroxylate 10-deoxoartemisinin, and a total of 35 hydroxylated products were identified. These can be grouped into dihydroxylated 10-deoxoartemisinins, monohydroxylated 10-deoxoartemisinins, hydroxylated dehydrogenated 10-deoxoartemisinins, and hydroxylated hydrogenated 10-deoxoartemisinins. Cunninghamella echinulata and Cunninghamella blakesleeana are able to hydroxylate 10-deoxoartemisinin, and their biotransformation products are investigated here for the first time. Cunninghamella elegans CICC 40250 was shown to most efficiently hydroxylate 10-deoxoartemisinin, and could serve as a model organism for microbial transformation. This method could be used to generate additional hydroxylated 10-deoxoartemisinins for further research.