Exploring the Biology of Plant Chemical Factory
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Understanding plant specialized metabolism and pathway engineering
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Plants produce an amazing diversity of specialized (i.e. secondary) metabolites that have applications as pharmaceuticals, pesticides, flavours and fragrances. These metabolites are biosynthesized and accumulated in tissue, organ and developmentally-specific manners, and also in response to pathogen attack and environmental perturbation, involving highly complex and sophisticated biosynthetic pathways. Comprehensive knowledge of the biosynthetic pathways and their regulation is pivotal to overcoming the low abundance of metabolites in the natural host and producing them in the heterologous host following modulation of the biosynthetic pathways. Our lab is interested in investigating the biosynthetic pathway enzymes and regulators that determine the spatio-temporal accumulation of medicinally important metabolites in plants, which are acclaimed in traditional medicine. Our current research includes unraveling plant terpene biosynthetic pathways and pathway engineering to reconstruct terpene pathways in alternate plant and microbial hosts.
(A)Â Transcriptomics and Metabolomics
The lack of genomic resources is a hindrance to understanding the specialized metabolite biosynthetic pathways in the majority of plants. To overcome this limitation, large-scale transcriptome (RNA-seq) data and expression sequence tags (ESTs) are generated for basil (Ocimum basilicum), kalmegh (Andrographis paniculata), banaba (Lagerstroemia speciosa), arjun (Terminalia arjuna), salai guggul (Boswellia serrata) and other medicinal plants. These data can be accessed in the NCBI (Plant Physiology, 2014; BMC Genomics, 2015; Plant Science, 2015; New Phytologist, 2017; Plant Science, 2020; The Plant Journal, 2021; Plant Molecular Biology, 2023). These transcriptome data (Illumina platform) are being mined and integrated with metabolomics (GC-MS/LC-MS) to identify key enzymes and regulators of the specialized metabolite biosynthetic pathways.
(B) Understanding Terpene Biosynthesis
A major aim of our lab has been to unravel how terpenes are spatiotemporally biosynthesized and accumulated in plants. Under this research program, our goal has been to know key enzymes and regulators of the terpene biosynthetic pathways in plants. We are employing an interdisciplinary approach using genomics, metabolomics, molecular biology, and biochemical tools to unravel key enzymes of the terpene biosynthetic pathways including terpene synthase, oxidosqualene cyclase, cytochrome P450 monooxygenases, glycosyltransferase, acyltransferase, etc. Until now we characterized biosynthetic pathway enzymes for monoterpenes, diterpenes and triterpenes in basil, kalmegh, banaba, salai guggul and arjuna (Plant Physiology, 2014; New Phytology, 2017 & 2019; Journal of Biological Chemistry, 2021; Plant Molecular Biology, 2023; Plant Science, 2015, 2020 & 2024; Plant Journal, 21 & 2024).
(C) Metabolic engineering & Synthetic Biology
Under the pathway elucidation program we have identified a suite of enzymes that are involved in the biosynthesis of valuable terpenes in medicinal plants. We are utilizing these enzymes to develop alternate hosts for the biosynthesis of valuable terpenes following synthetic biology and metabolic engineering approaches. We employ classical genome modification tools in yeast (Saccharomyces cerevisiae) for metabolic pathway engineering and strain improvement. We also explore genome editing (CRISPR-CAS9) approach to develop improved medicinal plants. We have demonstrated pathway reconstruction and biosynthesis of sesquiterpenes and triterpenes in S. cerevisiae and/or Nicotiana benthamiana by expressing plant enzymes (New Phytologist, 2017 & 2019; Plant journal, 2024; Appl Microbiol Biotechnol, 2024; Patent application 202311037138 ).
(D) Understanding the intricacies of terpene metabolism, plant growth-development & stress tolerance
Under this program, we are interested to know how terpene metabolism contributes to plant growth-development and stress tolerance. We are using various knock-out and gene overexpression lines to understand the cross-talk of terpene metabolism and plant growth and development. Our work found to role of diterpenoid in providing tolerance to insect herbivore in kalmegh (Plant Science, 2024)
