title: Structural and metabolic correlation for Bacillus megaterium ACBT03 in response to colchicine biotransformation.
abstract: This study aims to evaluate the effects of colchicine on metabolic and structural changes in Bacillus megaterium ACBT03, enduring colchicine bioconversion. Electron microscopy examination of cells adapted to different concentrations of colchicine for its bioconversion to pharmacologically active 3-demethylated colchicine, endowed changes in cell shape, decreased cell wall and plasma membrane thickness. In line with microscopic studies, lipid and membrane protein contents were drastically reduced in bacterial cells adapted to higher concentrations of colchicine and resulting into decrease in cell membrane thickness. More numbers of polyhydroxybutyrate (PHB) rich inclusion bodies were found inside the colchicine adapted cells and presence of higher amount of PHB, a carbon source for generation of redox potential, indicates that it might be responsible for activation of P450 BM-3 enzyme and plays significant role in colchicine demethylation. The presence of dense ribosome like bodies in colchicine adapted cells showed higher biosynthesis of P450 BM-3. Reduction in cell wall and cell membrane thickness, presence of more inclusion bodies and ribosome like masses in colchicine adapted cells were some of the key interlinked phenomena responsible for colchicine bioconversion. This is the first study which reports that colchicine demethylation process severely affects the structural and metabolic functions of the bacteria.
authors.affiliation: Industrial Biotechnology Laboratory, University Institute of Engineering & Technology M.D. University Rohtak 124001, Haryana, India.
authors.forename: Kashyap Kumar
authors.initials: KK
authors.lastname: Dubey
authors.forename: Arshad
authors.initials: A
authors.lastname: Jawed
authors.forename: Shafiul
authors.initials: S
authors.lastname: Haque
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000494:pharmacology; D001410:Bacillus megaterium / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000378:metabolism*; D001711:Biotransformation; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D002851:Chromatography, High Pressure Liquid; D003078:Colchicine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D006885:Hydroxybutyrates / Q000378:metabolism; D002479:Inclusion Bodies / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008563:Membrane Lipids / Q000032:analysis; D046529:Microscopy, Electron, Transmission; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy; D000091402:Prohibitins; D012270:Ribosomes / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001426:Bacterial Proteins; D006885:Hydroxybutyrates; D008563:Membrane Lipids; C000717328:PHB protein, human; D000091402:Prohibitins; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases; D003078:Colchicine