Cybernetic model assumes that a microorganism is an optimal strategist, sets goals, sub-goals and... more Cybernetic model assumes that a microorganism is an optimal strategist, sets goals, sub-goals and subsub-goals, monitors its performance against these goals and then takes remedial action. The soil bacterium Pseudomonas putida CSV86 is known for its ability to preferentially utilize aromatic compounds over glucose. We had set up a structured kinetic model where sub-goals are based on the environmental conditions. Upon exhaustion of the preferred hydrocarbon substrate, the organism sets a sub-goal of utilization of the less preferred glucose substrate and in-turn induces the relevant rate limiting enzymes. The model parameters were estimated from batch data and validated in the dynamic phase of a chemostat, which was subjected to pulse input of the preferred substrate. We find that the organism not only grows faster on the preferred hydrocarbon substrate but also adapts faster. Specifically, the rate of synthesis of the rate limiting enzyme for benzyl alcohol utilization is approximately seven times greater than that for glucose. The recovery time from the pulse of benzyl alcohol reduced dramatically with the increasing dilution rate. This is partially attributed to a higher enzyme synthesis rate at higher dilution rates in addition to the obvious effect of quicker benzyl alcohol washout.
Pseudomonas putida CSV86 utilizes aromatic compounds preferentially over sugars and co-metabolize... more Pseudomonas putida CSV86 utilizes aromatic compounds preferentially over sugars and co-metabolizes aromatics along with organic acids. In the present study, the metabolic capacity and adaptability of strain CSV86 were assessed in a chemostat at benzyl alcohol concentrations ranging from 1 g l(-1) to 3 g l(-1) and in the presence of glucose and succinate by systematically varying the dilution rate. Complete removal of benzyl alcohol was achieved for loadings up to 640 mg l(-1) h(-1) in presence of benzyl alcohol alone. The strain responded within 1 min towards step changes in substrate loading as indicated by an increase in the oxygen uptake rate, presumably as a result of excess metabolic capacity. These results suggest that CSV86 exhibits considerable metabolic elasticity upon increase in substrate load. Metabolic elasticity of the microorganism is an important parameter in wastewater treatment plants due to the changing substrate loads.
Cytochrome P450 mono-oxygenases (2UUQ) enzyme from Mycobacterium tuberculosis catalyzes oxidation... more Cytochrome P450 mono-oxygenases (2UUQ) enzyme from Mycobacterium tuberculosis catalyzes oxidation of organic compounds such as lipids and steroidal hormones therefore remain as potential drug target. Currently available first line anti-tuberculosis drugs have been caused several side effects in the body as well as resistance development by mycobacterium against these drugs, necessitates the considerable need for finding new drugs. Therefore, we propose a structure based computational method to find a new potential inhibitor for cytochrome P450 mono-oxygenases enzyme. Compounds from several ligand databases were docked against the functional sites of 2UUQ (A) through the standard GEMDOCK v2.0 and AUTODOCK4.0 molecular docking tools. Commercially available chemical compound ZINC00004165 (5-[3-(2-nitroimidazol-1-yl) propyl] phenanthridine) has produced top rank with lowest interaction energy of -113.2 (via GEMDOCK) and lowest docking energy of -9.80 kcal/mol (via AUTODOCK) as compared ...
The novel 3-methyladenine DNA glycosylase enzyme from oral pathogen Streptococcus sanguinisin inv... more The novel 3-methyladenine DNA glycosylase enzyme from oral pathogen Streptococcus sanguinisin involves in DNA repair mechanisms and participates in base excision repair. Its 3D structure is still unknown which may be a potential drug target, therefore here we proposed its putative 3D structure by homology modeling approach. EsyPred3d software produced more précised modeled structure as compare to Swiss model software. The modeled structure was further verified by PROCHECK analysis and subjected to functional site prediction servers for active site residues prediction. The functional site was further validated by molecular docking approach with ligand EDA (3-[2-Deoxyribofuranosyl] -3H-1, 3, 4, 5A, 8-Pentaaza-Asindacene-5monophosphate) from 1F4R. The EDR docked at the cavity of modeled structure of 3-methyladenine DNA glycosylase enzyme with highest Patchdock score of 3966 and lowest Autodock 4 docking energy of -10.30 Kcal/mol. The YA51, LA105, RA107 residues are surrounding the EDA and matching with ligand binding residues predicted by PROFUNC server. 139 designing against DNA glycosylase protein of oral pathogen Streptococcus sanguinis.
Several antibiotics have been discovered following the discovery of penicillin. These antibiotics... more Several antibiotics have been discovered following the discovery of penicillin. These antibiotics had been helpful in treatment of infectious diseases considered dread for centuries. The advent of multiple drug resistance in microbes has posed new challenge to researchers. The scientists are now evaluating alternatives for combating infectious diseases. This review focuses on major alternatives to antibiotics on which preliminary work had been carried out. These promising anti-microbial include: phages, bacteriocins, killing factors, antibacterial activities of non-antibiotic drugs and quorum quenching.
Cybernetic model assumes that a microorganism is an optimal strategist, sets goals, sub-goals and... more Cybernetic model assumes that a microorganism is an optimal strategist, sets goals, sub-goals and subsub-goals, monitors its performance against these goals and then takes remedial action. The soil bacterium Pseudomonas putida CSV86 is known for its ability to preferentially utilize aromatic compounds over glucose. We had set up a structured kinetic model where sub-goals are based on the environmental conditions. Upon exhaustion of the preferred hydrocarbon substrate, the organism sets a sub-goal of utilization of the less preferred glucose substrate and in-turn induces the relevant rate limiting enzymes. The model parameters were estimated from batch data and validated in the dynamic phase of a chemostat, which was subjected to pulse input of the preferred substrate. We find that the organism not only grows faster on the preferred hydrocarbon substrate but also adapts faster. Specifically, the rate of synthesis of the rate limiting enzyme for benzyl alcohol utilization is approximately seven times greater than that for glucose. The recovery time from the pulse of benzyl alcohol reduced dramatically with the increasing dilution rate. This is partially attributed to a higher enzyme synthesis rate at higher dilution rates in addition to the obvious effect of quicker benzyl alcohol washout.
Pseudomonas putida CSV86 utilizes aromatic compounds preferentially over sugars and co-metabolize... more Pseudomonas putida CSV86 utilizes aromatic compounds preferentially over sugars and co-metabolizes aromatics along with organic acids. In the present study, the metabolic capacity and adaptability of strain CSV86 were assessed in a chemostat at benzyl alcohol concentrations ranging from 1 g l(-1) to 3 g l(-1) and in the presence of glucose and succinate by systematically varying the dilution rate. Complete removal of benzyl alcohol was achieved for loadings up to 640 mg l(-1) h(-1) in presence of benzyl alcohol alone. The strain responded within 1 min towards step changes in substrate loading as indicated by an increase in the oxygen uptake rate, presumably as a result of excess metabolic capacity. These results suggest that CSV86 exhibits considerable metabolic elasticity upon increase in substrate load. Metabolic elasticity of the microorganism is an important parameter in wastewater treatment plants due to the changing substrate loads.
Cytochrome P450 mono-oxygenases (2UUQ) enzyme from Mycobacterium tuberculosis catalyzes oxidation... more Cytochrome P450 mono-oxygenases (2UUQ) enzyme from Mycobacterium tuberculosis catalyzes oxidation of organic compounds such as lipids and steroidal hormones therefore remain as potential drug target. Currently available first line anti-tuberculosis drugs have been caused several side effects in the body as well as resistance development by mycobacterium against these drugs, necessitates the considerable need for finding new drugs. Therefore, we propose a structure based computational method to find a new potential inhibitor for cytochrome P450 mono-oxygenases enzyme. Compounds from several ligand databases were docked against the functional sites of 2UUQ (A) through the standard GEMDOCK v2.0 and AUTODOCK4.0 molecular docking tools. Commercially available chemical compound ZINC00004165 (5-[3-(2-nitroimidazol-1-yl) propyl] phenanthridine) has produced top rank with lowest interaction energy of -113.2 (via GEMDOCK) and lowest docking energy of -9.80 kcal/mol (via AUTODOCK) as compared ...
The novel 3-methyladenine DNA glycosylase enzyme from oral pathogen Streptococcus sanguinisin inv... more The novel 3-methyladenine DNA glycosylase enzyme from oral pathogen Streptococcus sanguinisin involves in DNA repair mechanisms and participates in base excision repair. Its 3D structure is still unknown which may be a potential drug target, therefore here we proposed its putative 3D structure by homology modeling approach. EsyPred3d software produced more précised modeled structure as compare to Swiss model software. The modeled structure was further verified by PROCHECK analysis and subjected to functional site prediction servers for active site residues prediction. The functional site was further validated by molecular docking approach with ligand EDA (3-[2-Deoxyribofuranosyl] -3H-1, 3, 4, 5A, 8-Pentaaza-Asindacene-5monophosphate) from 1F4R. The EDR docked at the cavity of modeled structure of 3-methyladenine DNA glycosylase enzyme with highest Patchdock score of 3966 and lowest Autodock 4 docking energy of -10.30 Kcal/mol. The YA51, LA105, RA107 residues are surrounding the EDA and matching with ligand binding residues predicted by PROFUNC server. 139 designing against DNA glycosylase protein of oral pathogen Streptococcus sanguinis.
Several antibiotics have been discovered following the discovery of penicillin. These antibiotics... more Several antibiotics have been discovered following the discovery of penicillin. These antibiotics had been helpful in treatment of infectious diseases considered dread for centuries. The advent of multiple drug resistance in microbes has posed new challenge to researchers. The scientists are now evaluating alternatives for combating infectious diseases. This review focuses on major alternatives to antibiotics on which preliminary work had been carried out. These promising anti-microbial include: phages, bacteriocins, killing factors, antibacterial activities of non-antibiotic drugs and quorum quenching.
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Papers by Anshul Nigam