Understanding the biological role of PqqB in Pseudomonas stutzeri using molecular dynamics simulation approach.

Phosphate solubilization is an important and widely studied plant growth promoting trait exhibited by many bacteria. Pyrroloquinoline quinone (PQQ), a redox cofactor of methanol and glucose dehydrogenases has been well established as essential for phosphate solubilization. PQQ operon has been well studied in growth promoting rhizobacteria like Pseudomonas spp., Gluconobacter oxydans, Klebsiella pneumoniae, etc. However, the role of PqqB is quite ambiguous as its functional role has been contradicted in many studies. In the present study, we selected Pseudomonas stutzeri - a well-known P solubilizing bacterium as a representative species of the Pseudomonas genus on the basis of phylogenetic and statistical analyses of PqqB proteins. A 3 D model was generated for this protein. Docking of PqqB with PQQ showed good interaction with a theoretical binding affinity of -7.4 kcal/mol. On the other hand, docking of PqqC with 3a-(2-amino-2-carboxy-ethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydro-quinoline-7,9-dicarboxylic acid (AHQQ, immediate precursor of PQQ) showed strong interaction (-10.4 kcal/mol) but the same was low with PQQ (-6.4 kcal/mol). Molecular dynamic simulation of both the complexes showed stable conformation. The binding energy of PqqB-PQQ complex (-182.710 ± 16.585 kJ/mol) was greater than PqqC-PQQ complex (-166.114 ± 12.027 kJ/mol). The results clearly indicated that kinetically there is a possibility that after cyclization of AHQQ to PQQ by PqqC, PQQ can be taken up by PqqB and transported to periplasm for the oxidation of glucose. To the best of our knowledge, this is the first attempt to understand the biological role of PqqB on the basis of molecular interactions and dynamics.Communicated by Ramaswamy H. Sarma.

Bioactive antifungal metabolites produced by Streptomyces amritsarensis V31 help to control diverse phytopathogenic fungi.

Actinomycetes due to their unique repertoire of antimicrobial secondary metabolites can be an eco-friendly and sustainable alternative to agrochemicals to control plant pathogens. In the present study, antifungal activity of twenty different actinomycetes was evaluated via dual culture plate assay against six different phytopathogens, viz., Alternaria alternata, Aspergillus flavus, Fusarium oxysporum f. sp. lycopersici, Sarocladium oryzae, Sclerotinia sclerotiorum, and Rhizoctonia solani. Two potential isolates, Streptomyces amritsarensis V31 and Kribella karoonensis MSCA185 showing high antifungal activity against all six fungal pathogens, were further evaluated after extraction of bioactive metabolites in different solvents. Metabolite extracted from S. amritsarensis V31 in different solvents inhibited Rhizoctonia solani (7.5-65%), Alternaria alternata (5.5-52.7%), Aspergillus flavus (8-30.7%), Fusarium oxysporum f. sp. lycopersici (25-44%), Sarocladium oryzae (11-55.5%), and Sclerotinia sclerotiorum (29.7-40.5%); 1000 D diluted methanolic extract of S. amritsarensis V31 showed growth inhibition against R. solani (23.3%), A. flavus (7.7%), F. oxysporum (22.2%), S. oryzae (16.7%), and S. sclerotiorum (19.0%). Metabolite extracts of S. amritsarensis V31 significantly reduced the incidence of rice sheath blight both as preventive and curative sprays. Chemical profiling of the metabolites in DMSO extract of S. amritsarensis V31 revealed 6-amino-5-nitrosopyrimidine-2,4-diol as the predominant compound present. It was evident from the LC-MS analyses that S. amritsarensis V31 produced a mixture of potential antifungal compounds which inhibited the growth of different phytopathogenic fungi. The results of this study indicated that metabolite extracts of S. amritsarensis V31 can be exploited as a bio-fungicide to control phytopathogenic fungi.

In silico analysis reveals the anti-malarial potential of quinolinyl chalcone derivatives.

In this study, the correlation between chemical structures and various parameters such as steric effects and electrostatic interactions to the inhibitory activities of quinolinyl chalcone derivatives is derived to identify the key structural elements required in the rational design of potent and novel anti-malarial compounds. The molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are carried out on 38 chalcones derivatives using Plasmodium falciparum lactate dehydrogenase (PfLDH) as potential target. Surflex-dock is used to determine the probable binding conformations of all the compounds at the active site of pfLDH and to identify the hydrogen bonding interactions which could be used to alter the inhibitory activities. The CoMFA model has provided statistically significant results with the cross-validated correlation coefficient (q(2)) of .850 and the non-cross-validated correlation coefficient (r(2)) of .912. Standard error of estimation (SEE) is .280 and the optimum number of component is five. The predictive ability of the resultant model is evaluated using a test set comprising of 13 molecules and the predicted r(2) value is .885. The results provide valuable insight for optimization of quinolinyl chalcone derivatives for better anti-malarial therapy.