@article { ISI:000297606200009, title = {Comparative and chemical proteomic approaches reveal gatifloxacin deregulates enzymes involved in glucose metabolism}, journal = {Journal of Toxicological Sciences}, volume = {36}, number = {6}, year = {2011}, month = {DEC}, pages = {787-796}, publisher = {JAPANESE SOC TOXICOLOGICAL SCIENCES}, address = {INTERNATIONAL MEDICAL INFORMATION CENTER, SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI, SHINJUKU-KU, TOKYO, 160-0016, JAPAN}, abstract = {

Gatifloxacin has been associated with increased risks of hypoglycemic and hyperglycemic side effects. In order to understand the molecular mechanism of gatifloxacin induced deregulation of glucose metabolism, a Combination of comparative and chemical proteomic approaches were employed using yeast as a model system. Differential protein expression studies using two dimensional electrophoresis and mass spectrometry reveal that gatifloxacin deregulates the expression of key enzymes involved in glucose metabolism. Furthermore, affinity chromatography and LC-MSE analysis led to identification of enolase, as one of the key gatifloxacin binding proteins. Fluorescence spectrometric studies confirmed that the gatifloxacin indeed binds to enolase. Role of enolase in regulation of gatifloxacin induced dysglycemic effect is discussed.

}, keywords = {antibiotics, Differential protein expression, Fluoroquinolone, Glycolysis, Yeast}, issn = {0388-1350}, doi = {10.2131/jts.36.787}, author = {Suresh, Kesavan K. and Bhosale, Santosh D. and Thulasiram, Hirekodathakallu V. and Kulkarni, Mahesh J.} } @article { ISI:000348833400001, title = {Characterization of 10-hydroxygeraniol dehydrogenase from catharanthus roseus reveals cascaded enzymatic activity in iridoid biosynthesis}, journal = {Scientific Reports}, volume = {5}, year = {2015}, month = {FEB}, pages = {Article Number: 8258}, publisher = {NATURE PUBLISHING GROUP}, address = {MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND}, abstract = {

Catharanthus roseus [L.] is a major source of the monoterpene indole alkaloids (MIAs), which are of significant interest due to their therapeutic value. These molecules are formed through an intermediate, cis-trans-nepetalactol, a cyclized product of 10-oxogeranial. One of the key enzymes involved in the biosynthesis of MIAs is an NAD(P)(+) dependent oxidoreductase system, 10-hydroxygeraniol dehydrogenase (Cr10HGO), which catalyses the formation of 10-oxogeranial from 10-hydroxygeraniol via 10-oxogeraniol or 10-hydroxygeranial. This work describes the cloning and functional characterization of Cr10HGO from C. roseus and its role in the iridoid biosynthesis. Substrate specificity studies indicated that, Cr10HGO has good activity on substrates such as 10-hydroxygeraniol, 10-oxogeraniol or 10-hydroxygeranial over monohydroxy linear terpene derivatives. Further it was observed that incubation of 10-hydroxygeraniol with Cr10HGO and iridoid synthase (CrIDS) in the presence of NADP(+) yielded a major metabolite, which was characterized as (1R, 4aS, 7S, 7aR)-nepetalactol by comparing its retention time, mass fragmentation pattern, and co-injection studies with that of the synthesized compound. These results indicate that there is concerted activity of Cr10HGO with iridoid synthase in the formation of (1R, 4aS, 7S, 7aR)-nepetalactol, an important intermediate in iridoid biosynthesis.

}, issn = {2045-2322}, doi = {10.1038/srep08258}, author = {Krithika, Ramakrishnan and Srivastava, Prabhakar Lal and Rani, Bajaj and Kolet, Swati P. and Chopade, Manojkumar and Soniya, Mantri and Thulasiram, Hirekodathakallu V.} } @article {42999, title = {Comparative functional characterization of eugenol synthase from four different ocimum species: implications on eugenol accumulation}, journal = {Biochimica Et Biophysica Acta-Proteins and Proteomics}, volume = {1864}, year = {2016}, month = {NOV}, pages = {1539-1547}, abstract = {

Isoprenoids and phenylpropanoids are the major secondary metabolite constituents in Ocimum genus. Though enzymes from phenylpropanoid pathway have been characterized from few plants, limited information exists on how they modulate levels of secondary metabolites. Here, we performed phenylpropanoid profiling in different tissues from five Ocimum species, which revealed significant variations in secondary metabolites including eugenol, eugenol methyl ether, estragole and methyl cinnamate levels. Expression analysis of eugenol synthase (EGS) gene showed higher transcript levels especially in young leaves and inflorescence; and were positively correlated with eugenol contents. Additionally, transcript levels of coniferyl alcohol acyl transferase, a key enzyme diverting pool of substrate to phenylpropanoids, were in accordance with their abundance in respective species. In particular, eugenol methyl transferase expression positively correlated with higher levels of eugenol methyl ether in Ocimum tenuiflorum. Further, EGSs were functionally characterized from four Ocimum species varying in their eugenol contents. Kinetic and expression analyses indicated, higher enzyme turnover and transcripts levels, in species accumulating more eugenol. Moreover, biochemical and bioinformatics studies demonstrated that coniferyl acetate was the preferred substrate over coumaryl acetate when used, individually or together, in the enzyme assay. Overall, this study revealed the preliminary evidence for varied accumulation of eugenol and its abundance over chavicol in these Ocimum species. Current findings could potentially provide novel insights for metabolic modulations in medicinal and aromatic plants. (C) 2016 Elsevier B.V. All rights reserved.

}, doi = {10.1016/j.bbapap.2016.08.004}, author = {Anand, Atul and Jayaramaiah, Ramesha H. and Beedkar, Supriya D. and Singh, Priyanka A. and Joshi, Rakesh S. and Mulani, Fayaj A. and Dholakia, Bhushan B. and Punekar, Sachin A. and Gade, Wasudeo N. and Thulasiram, Hirekodathakallu V. and Giri, Ashok P.} } @article {48480, title = {Comprehensive analysis of physiological and metabolomic responses to drought reveals specific modulation of acquired tolerance mechanisms in rice}, journal = {Physiologia Plantarum}, volume = {175}, year = {2023}, month = {MAY}, pages = {e13917}, type = {Article}, abstract = {

Mild stresses induce {\textquoteleft}{\textquoteleft}acquired tolerance traits{\textquoteright}{\textquoteright} (ATTs) that provide tolerance when stress becomes severe. Here, we identified the genetic variability in ATTs among a panel of rice germplasm accessions and demonstrated their relevance in protecting growth and productivity under water-limited conditions. Diverse approaches, including physiological screens, association mapping and metabolomics, were adopted and revealed 43 significant marker-trait associations. Nontargeted metabolomic profiling of contrasting genotypes revealed 26 {\textquoteleft}{\textquoteleft}tolerance-related-induced{\textquoteright}{\textquoteright} primary and secondary metabolites in the tolerant genotypes (AC-39000 and AC-39020) compared to the susceptible one (BPT-5204) under water-limited condition. Metabolites that help maintain cellular functions, especially Calvin cycle processes, significantly accumulated more in tolerant genotypes, which resulted in superior photosynthetic capacity and hence water use efficiency. Upregulation of the glutathione cycle intermediates explains the ROS homeostasis among the tolerant genotypes, maintaining spikelet fertility, and grain yield under stress. Bioinformatic dissection of a major effect quantitative trait locus on chromosome 8 revealed genes controlling metabolic pathways leading to the production of osmolites and antioxidants, such as GABA and raffinose. The study also led to the identification of specific trait donor genotypes that can be effectively used in translational crop improvement activities.

}, issn = {0031-9317}, doi = {10.1111/ppl.13917}, author = {Doddaraju, Pushpa and Dharmappa, Prathibha M. and Thiagarayaselvam, Aarthy and Vijayaraghavareddy, Preethi and Bheemanahalli, Raju and Basavaraddi, Priyanka A. and Malagondanahalli, Mohan Kumar V. and Kambalimath, Sumanth and Thulasiram, Hirekodathakallu V. and Sreeman, Sheshshayee M.} }