Whey valorization for sustainable polyhydroxyalkanoate production by Bacillus megaterium: Production, characterization and in vitro biocompatibility evaluation.

Polyhydroxyalkanoates (PHAs) are biodegradable biopolymers acclaimed as an eco-friendly substitute of hazardously polluting petrochemical plastics. Using industrial by-products as PHA feedstocks could improve its process economics and market implementation. Valorizing the plenteous, nutritive pollutant whey as PHA production feedstock would be an excellent whey management strategy. This study aimed at whole/crude whey valorization for value-added PHA production using B. megaterium Ti3 innate protease, alleviating pretreatments. Response surface methodology (RSM) media optimization ascertained whey (%) as the key influential factor (p < 0.05). The optimized and validated RSM model (R2, 0.991; desirability, 1) facilitated 12.2, 11.5 folds increased PHA yield (2.20 ± 0.11 g/L) and productivity (0.05 gPHA/L/h). A positive correlation (r2, 0.95 and 0.87) was observed amid the innate enzymes (protease and lipase) and PHA production. The PHA was characterized by 1H and 13C NMR, GPC, TGA, and was identified as poly (3-hydroxybutyrate) (P3HB) by NMR. A significantly reduced roughness (110 ± 5.6 nm); increased hydrophilicity (8.6 ± 0.3 and 8.7 ± 0.5%), protein adsorption (68.75 ± 2.55 µg/cm2) and 1.6 folds higher biocompatibility achieved on poly (ethylene glycol) (PEG) blending compared to neat P3HB films. This is the first report on B. megaterium innate enzyme based whey valorization to PHAs also demonstrating its biomedical applicability.

Modulation of Bax and Bcl-2 genes by secondary metabolites produced by Penicillium rubens JGIPR9 causes the apoptosis of cancer cell lines.

Search for an efficient anti-cancer compound of natural origin with well-defined mechanisms of action is an important scientific pursuit today, due to cancer being the second leading cause for the death of affected people. The members of the genus Penicillium are one of the important sources of bioactive compounds. In the present study, Penicillium rubens, isolated from a garden soil in Madurai district of Tamil Nadu, was found to produce a highly promising anti-cancer metabolite. The percentage viabilities of HepG2, HeLa and MCF-7 cancer cells treated with the bioactive fraction (P5) isolated from P. rubens, ranged between 40-50% after 96 h. Apoptosis induction was found to be the major reason for the observed reduction in cancer cell proliferation and cell count which was confirmed by caspase activity, DNA fragmentation, clonogenic assay, cell cycle analysis and LDH assays. The upregulation of proapoptotic Bax, coupled with the downregulation of anti-apoptotic Bcl-2 expressions were confirmed by RT-qPCR and flow cytometry methods. The current study also indicated an upregulation of p53 which further strengthened the apoptogenic property of P5 fraction. Non-toxicity of P5 was demonstrated on normal peripheral lymphocytes. The analysis of P5 fraction through GC-MS indicated the presence of indole-2, 3-(4,4-dimethyl-3-thiosemicarbazone) as one of the major compounds.