Beside anti-cholesterol activity, lovastatin garners worldwide attention for therapeutical application against various diseases especially cancer. A total of 36 filamentous fungi from soil samples were isolated and screened for lovastatin production by yeast growth bioassay method. C9 strain (later identified as was screened as potential strain of lovastatin production. Further confirmation of the compound was made using TLC, HPTLC and HPLC in which similar Rf value, densitogram peak and chromatogram peak against the standard lovastatin were observed, respectively. The purified lovastatin subjected for IR analysis showed a lactone ring peak at 1763.63 cm similar to standard lovastatin. Further structural analysis including NMR and LC-MS of the purified lovastatin reassures the molecular formula and molecular weight similar to standard. In quantitative terms, and produced 1.4 mg g DWS, 0.83 mg g DWS and 0.3 mg g DWS of lovastatin, respectively, ( < 0.0001) without any optimization. Lovastatin showed significant antioxidant property with IC: 145.9 µg mL (140 µL), and the percentage of inhibition is maximum at 199.5 µg/mL which is statistically significant ( < 0.0001).
Objective: The objective of the present study is to evaluate the anticancer potential of lovastatin obtained from fungal source.Methods: About 15 fungal cultures were isolated from soil samples collected from Bharathiar University, India, and all are identified and characterized through microscopic characterization. Lovastatin producing capability was confirmed through bioassay against Saccharomyces cerevisiae, and the ability of selected fungus to produce lovastatin was further confirmed by high-performance liquid chromatography. Maximum lovastatin producing fungi were further selected for purification (overloaded elution chromatography) and characterization done using inhibition rate (IR). 5-diphenyl tetrazolium bromide (MTT) assay using A549 cell line was performed for antitumor activity evaluation.Results: Among the 15 isolates, Aspergillus flavus exhibited the maximum zone of inhibition (1.5 cm) against the test organism through solid-state fermentation. The resemblance in retention time (RT) of peak shown in chromatograms of standard lovastatin (RT=25.1 minutes) and sample (RT=25.1 minutes) were similar. This confirmed the presence of lovastatin in the selected fungal isolate (A. flavus). The presence of two functional groups in lovastatin C=O and O-H was confirmed by IR spectrum 50% of cell lysis was observed in MTT assay.Conclusion: Lovastatin obtained from soil fungi is capable of producing lovastatin in good proportions. Obtained fungal lovastatin exhibited significant antitumor activity against A549 cell line. Like other biological derivatives, lovastatin from soil fungi had greater potential in anticancer activity, and further biosynthetic pathway insights in their production can improve the yield which aid in large scale production.
The aim of this study was the modification of lovastatin by microbes to improve its potential. Actinobacteria exhibit staggering diversity in terms of their biosynthetic capability for specialized metabolites which has been traced back to the presence of specialized gene clusters. The objective of the study is to exploit the potential of Actinobacteria strain(s), which can biotransform lovastatin to simvastatin, which might be a more potent therapeutic agent than lovastatin. We have screened 40 Actinobacteria strains and assessed their biotransformation potential primarily through thin layer chromatography (TLC) analysis, followed by high performance thin layer chromatography and high performance liquid chromatography analysis. One strain C7 (CTL S12) has been identified as a potential Actinobacteria that favored the simvastatin biotransformation. The morphological and biochemical analysis together with 16S rRNA sequencing coupled with phylogenetic analysis confirmed the ideal strain (C7) as Streptomyces carpaticus. Successively, the purified simvastatin from S. carpaticus was characterized by liquid chromatography–mass spectrometry (LC–MS), infrared spectrometry, nuclear magnetic resonance, and HMG‐CoA assay. In the LC–MS analysis, a peak at 419.24 m/z confirmed the elemental composition of simvastatin (C25H39O5). In HMG‐CoA assay, the IC50 of simvastatin was 50 μg/ml, and the inhibitory potential was 1.36 times higher compared to that of lovastatin. Thus, the biotransformation of simvastatin from lovastatin by S. carpaticus is reported for the first time.
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.
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