Research Focus
Our current interests are related to different aspects of glutathione and sulphur metabolism in yeasts. Glutathione, γ-glutamyl cysteinyl glycine, an unusual thiol containing tripeptide that is present in high concentrations in almost all eukaryotic cells, plays multiple roles including protection from oxidative stress, maintenance of the cellular redox buffer, in mitochondrial iron-sulphur metabolism, in gene regulation, and in metal and drug detoxification. Glutathione metabolism is intimately linked to sulphur metabolism owing to the presence of the key cysteine residue, and we thus also investigate aspects of sulphur metabolism related to glutathione homeostasis. Our principal focus is on understanding how glutathione levels are maintained in the cell, and we are examining different pathways that contribute towards this maintenance. This includes the high affinity plasma membrane transporter of glutathione that was identified in our lab, the classical and two recently discovered non-classical pathways of glutathione degradation (also discovered in our lab) biosynthesis, organellar compartmentalization and utilization of glutathione. We are attempting to not only understand these different pathways and their regulation in detail, but are interested in integrating these pathways and their regulation into a larger picture of glutathione homeostasis in living cells.
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Selected Publications
- Adusumilli SH, Dabburu GR, Kumar M, Arora P, Chattopadhyaya B, Behera D, Bachhawat A.K. (2024) The potential of R. toruloides mevalonate pathway genes in increasing isoprenoid yields in S. cerevisiae: Evaluation of GGPPS and HMG-CoA reductase. Enzyme Microb Technol. 2024.174:110374. doi: 10.1016/j.enzmictec.2023.110374.
- Suyal S, Choudhury C, Bachhawat A.K. (2023) The ChaC1 active site: Defining the residues and determining the role of ChaC1-exclusive residues in the structural and functional stability. Proteins. 91,567-580, 2023
- Muskan Bhatia, Jyotika Thakur, Shradha Suyal, Ruchika Oniel, Rahul Chakraborty, Shalini Pradhan, Monika Sharma, Shantanu Sengupta, Sunil Laxman, Shyam Kumar Masakapalli, Anand Kumar Bachhawat (2020). Allosteric inhibition of MTHFR prevents futile SAM cycling and maintains nucleotide pools in one carbon metabolism. J Biol Chem , 295, 16037-16057
- Bachhawat AK, Yadav S.(2018) The glutathione cycle: Glutathione metabolism beyond the γ-glutamyl cycle. IUBMB Life. 70(7):585-592
- Kaur A, Gautam R, Srivastava R, Chandel A, Kumar A, Karthikeyan,S and Bachhawat AK (2017) , ChaC2: An Enzyme for Slow Turnover of Cytosolic Glutathione. J. Biol.Chem 292:638-651,201
- Kumar, C, Igbaria, A, D'Autreaux, B., Planson, A-G., Junot, C., Bachhawat, AK, Deluanay-Moisan, A and Toledano, M. 2011. Glutathione revisited : a vital function in iron metabolism but a secondary role in thiolredox maintenance. EMBO J. 30: 2044-56.
- Yadav, AK and Bachhawat, AK. 2011. CgCYN1, a plasma membrane cystine-specific transporter of Candida glabrata with orthologues prevalent amongst pathogenic yeasts and fungi. J Biol Chem. 286:19714-23.
- Desai PR, Thakur A, Ganguli D, Paul S, Morschhauser J, Bachhawat AK. 2011. Glutathione utilization by Candida albicans requires a functional DUG pathway and OPT7, an unusual member of the oligopeptide transporter family.
J Biol Chem. 286:41183-94.
- Kaur H, Ganguli D, Bachhawat AK. 2012. Glutathione degradation by the alternative pathway (DUG pahway) in Saccharomyces cerevisiae is initiated by the (Dug2p-Dug3p)2 complex, a novel GATase enzyme acting on glutathione. J Biol Chem. 287: 8920-8931.
- Kumar, S., Kushwaha,H., Bachhawat,AK, Raghava,GPS, Ganesan, K 2012. Genome sequence of the oleaginous red yeast Rhodosporodium toruloides MTCC457. Eukaryotic Cell ( In Press)
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