Prior to undertaking his PhD, Kuzhiumparambil was employed as a scientist at the Centre for Medicinal Plants Research (India) where he was actively engaged in an number of research activities including: chemical profiling of medicinal plants used in traditional medicine; isolation and characterisation of biomarkers; and substitution studies of raw drugs used in herbal pharmaceutical Industry. During this period (2004–2006), he published six research papers in the field of chromatography method development and biomarker studies.
Between 2007–2011 Kuzhiumparambil undertook a PhD in a drug discovery project – Chemical and Biological studies of Traditional Medicinal Plants – under the supervision of Prof. Joanne Jamie at Macquarie University. He was awarded a Macquarie University Research Excellence Scholarship to undertake this research.
After graduating in 2011, Kuzhiumparambil started his post-doctoral position with A/Prof. Shanlin Fu in the area of sports drug testing and doping control analysis. In 2012, together with with A/Prof. Fu he was awarded an Australian Doping Control Program (ADRP) grant for $157k. In this project, he investigated the implication of using oxidising adulterants to mask steroid abuse, and he isolated several biomarkers that could be used in doping control laboratories.
In 2015, Kuzhiumparambil joined the Climate Change Cluster (C3), University of Technology Sydney as a research associate. He is the Project Manager for Bioremediation (Chemistry) Program and leads the chemistry component of multiple research projects. He works across multiple research groups, answering chemistry questions, which includes, method development and analysis of analytes of interest such as hormones, pigments, oxylipins, fatty acids, and polyamines in various marine organisms. He is also involved in high value product development from microalgae, and has established protocols for targeted and untargeted metabolomic and lipidomic analysis.
- Chartered Member of the Royal Australian Chemical Institute
- Member of The International Association of Forensic Toxicologists
- Member of Forensic and Clinical Toxicology Association
Can supervise: YES
Metabolomics and lipidomic analysis of microalgae and seagrasses
Isolation and characterisation of bioactive molecules
Bodachivskyi, I, Kuzhiumparambil, U & Bradley G Williams, D 2019, 'High Yielding Acid-Catalysed Hydrolysis of Cellulosic Polysaccharides and Native Biomass into Low Molecular Weight Sugars in Mixed Ionic Liquid Systems.', ChemistryOpen, vol. 8, no. 10, pp. 1316-1324.View/Download from: UTS OPUS or Publisher's site
Ionic media comprising 1-butyl-3-methylimidazolium chloride and the acidic deep eutectic solvent choline chloride/oxalic acid as co-solvent-catalyst, very efficiently convert various cellulosic substrates, including native cellulosic biomass, into water-soluble carbohydrates. The optimum reaction systems yield a narrow range of low molecular weight carbohydrates directly from cellulose, lignocellulose, or algal saccharides, in high yields and selectivities up to 98 %. Cellulose possesses significant potential as a renewable platform from which to generate large volumes of green replacements to many petrochemical products. Within this goal, the production of low molecular weight saccharides from cellulosic substances is the key to success. Native cellulose and lignocellulosic feedstocks are less accessible for such transformations and depolymerisation of polysaccharides remains a primary challenge to be overcome. In this study, we identify the catalytic activity associated with selected deep eutectic solvents that favours the hydrolysis of polysaccharides and develop reaction conditions to improve the outcomes of desirable low molecular weight sugars. We successfully apply the chemistry to raw bulk, non-pretreated cellulosic substances.
Bodachivskyi, I, Kuzhiumparambil, U & Williams, DBG 2019, 'A Systematic Study of Metal Triflates in Catalytic Transformations of Glucose in Water and Methanol: Identifying the Interplay of Bronsted and Lewis Acidity', CHEMSUSCHEM, vol. 12, no. 14, pp. 3263-3270.View/Download from: UTS OPUS or Publisher's site
Bodachivskyi, I, Kuzhiumparambil, U & Williams, DBG 2019, 'A Systematic Study of Metal Triflates in Catalytic Transformations of Glucose in Water and Methanol: Identifying the Interplay of Brønsted and Lewis Acidity', ChemSusChem, vol. 12, pp. 3208-3208.View/Download from: UTS OPUS or Publisher's site
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Invited for this month′s cover is the group of Prof. Bradley Williams at the University of Technology Sydney. The image depicts the manifold products that can be selected in transformations of glucose through manipulation of the Brønsted or Lewis acidity of the catalyst. The Full Paper itself is available at 10.1002/cssc.201900292.
Bodachivskyi, I, Kuzhiumparambil, U & Williams, DBG 2019, 'Acid-Catalysed Conversion of Carbohydrates into Furan-Type Molecules in Zinc Chloride Hydrate', ChemPlusChem, vol. 84, no. 4, pp. 352-357.View/Download from: UTS OPUS or Publisher's site
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Acid-catalysed conversion of biomass, specifically cellulose, holds promise to create value-added, renewable replacements for many petrochemical products. We investigated an unusual acid-catalysed transformation of cellulose and cellobiose in the biphasic solvent system zinc chloride hydrate (ionic liquid)/anisole. Here, furyl hydroxymethyl ketone and furfural are obtained as major products, which are valuable but less commonly formed in high yields in transformations of cellulosic substrates. We explored this chemistry in small-scale model reactions and applied the optimised methods to the conversion of cellulose in bench-scale processes. The optimum reaction system and preferred reaction conditions are defined to select for highly desirable furanoid products in the highest known yields (up to 46 %) directly from cellulose or cellobiose. The method avoids the use of added catalysts: the ionic solvent zinc chloride hydrate possesses the intrinsic acidity required for the hydrolysis and chemical transformation steps. The process involves inexpensive media for the catalytic conversion of cellulose into high-value products under mild processing conditions.
Bodachivskyi, I, Kuzhiumparambil, U & Williams, DBG 2019, 'Metal triflates are tunable acidic catalysts for high yielding conversion of cellulosic biomass into ethyl levulinate', Fuel Processing Technology, vol. 195.View/Download from: UTS OPUS or Publisher's site
© 2019 Metal triflates and their mixtures with Brønsted acids are excellent catalysts for the selective and high yielding transformation of microcrystalline cellulose into ethyl levulinate, in ethanol, producing synergistic catalyst effects in some instances. The pretreatment of raw and unrefined cellulosic materials with a deep eutectic solvent enables similarly excellent catalysed conversion thereof into ethyl levulinate in superb yield (up to 75%) and selectivity (up to 88%). When using fermentation-derived ethanol, the product possesses 100% renewable content.
Bodachivskyi, I, Kuzhiumparambil, U & Williams, DBG 2019, 'The role of the molecular formula of ZnCl2·: N H2O on its catalyst activity: A systematic study of zinc chloride hydrates in the catalytic valorisation of cellulosic biomass', Catalysis Science and Technology, vol. 9, no. 17, pp. 4693-4701.View/Download from: UTS OPUS or Publisher's site
© The Royal Society of Chemistry 2019. We demonstrate the efficient and direct transformation of a range of low value substrates, such as lignocellulose and algal biomass, into significantly higher value chemicals, including low molecular weight reducing saccharides, 5-(hydroxymethyl)furfural, furyl hydroxymethyl ketone and furfural. This is based on a systematic study of ZnCl2·nH2O (n = 2.5-4.5), in particular the role of the molecular formula (the amount of H2O) on its activity in the catalytic transformation of cellulosic materials into value added small molecules. The study includes various model transformations based on refined saccharides and applies the new insights to the highly selective transformation of raw biomass.
Buapet, P, Mohammadi, NS, Pernice, M, Kumar, M, Kuzhiumparambil, U & Ralph, PJ 2019, 'Excess copper promotes photoinhibition and modulates the expression of antioxidant-related genes in Zostera muelleri', AQUATIC TOXICOLOGY, vol. 207, pp. 91-100.View/Download from: UTS OPUS or Publisher's site
Commault, AS, Fabris, M, Kuzhiumparambil, U, Adriaans, J, Pernice, M & Ralph, PJ 2019, 'Methyl jasmonate treatment affects the regulation of the 2-C-methyl-D-erythritol 4-phosphate pathway and early steps of the triterpenoid biosynthesis in Chlamydomonas reinhardtii', Algal Research, vol. 39.View/Download from: UTS OPUS or Publisher's site
© 2019 Elsevier B.V. Terpenoids are a large and diverse class of naturally occurring metabolites serving many industrial applications and natural roles. Economically important terpenoids are often produced in low abundance from their natural sources, making their industrial-scale production challenging or uneconomical, therefore engineered microorganisms are frequently used as heterologous production platforms. Photosynthetic microorganisms, such as the green alga Chlamydomonas reinhardtii, represent promising systems to produce terpenoids in a cost-effective and sustainable manner, but knowledge about the regulation of their terpenoid metabolism remains limited. Here we report on the investigation of the phytohormone methyl jasmonate (MeJA) as elicitor of algal terpenoid synthesis. We treated C. reinhardtii cells in mid-exponential growth phase with three different concentrations of MeJA (0.05, 0.5 and 1 mM). The highest concentration of MeJA affected the photosynthetic activity of the cells, arrested the growth and up-regulated key genes of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, leading to a significant increase in intermediates of this pathway, squalene and (S)-2,3-epoxysqualene, while the abundance of cycloartenol, and two main sterols (ergosterol and 7-dehydroporiferasterol) decreased. These data suggest the redirection of the carbon flux towards the synthesis of yet uncharacterised triterpenoid secondary metabolites upon MeJA treatment. Our results offer important new insights into the regulation of the triterpenoid metabolism in C. reinhardtii and raise important questions on hormonal signalling in microalgae. Phytohormone treatment is tested for the first time in algae, where it holds great potential for identifying key transcriptional regulators of the MEP pathway as targets for future metabolic engineering studies for improve production of high-value triterpenoids.
Curson, ARJ, Williams, BT, Pinchbeck, BJ, Sims, LP, Martínez, AB, Rivera, PPL, Kumaresan, D, Mercadé, E, Spurgin, LG, Carrión, O, Moxon, S, Cattolico, RA, Kuzhiumparambil, U, Guagliardo, P, Clode, PL, Raina, J-B & Todd, JD 2019, 'Author Correction: DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton.', Nature microbiology, vol. 4, no. 3, pp. 540-542.View/Download from: UTS OPUS or Publisher's site
In the version of this Letter originally published, the Methods incorrectly stated that all phytoplankton cultures were sampled in mid-exponential phase. The low-nitrogen cultures were sampled in early stationary phase and at the point at which Fv/Fm values decreased, to indicate that cultures were experiencing low-nitrogen conditions. All other phytoplankton cultures were sampled in exponential phase. Growth and Fv/Fm data are provided here on high- and low-nitrogen cultures (Figs 1, 2 and 3) to clarify and support this correction. The Methods also stated that cell counting was done using a Beckman Multisizer 3 Coulter Counter, but a CASY Model TT Cell Counter was used.
Leggat, WP, Camp, EF, Suggett, DJ, Heron, SF, Fordyce, AJ, Gardner, S, Deakin, L, Turner, M, Beeching, LJ, Kuzhiumparambil, U, Eakin, CM & Ainsworth, TD 2019, 'Rapid Coral Decay Is Associated with Marine Heatwave Mortality Events on Reefs.', Current biology : CB, vol. 29, no. 16, pp. 2723-2730.View/Download from: UTS OPUS or Publisher's site
Severe marine heatwaves have recently become a common feature of global ocean conditions due to a rapidly changing climate [1, 2]. These increasingly severe thermal conditions are causing an unprecedented increase in the frequency and severity of mortality events in marine ecosystems, including on coral reefs . The degradation of coral reefs will result in the collapse of ecosystem services that sustain over half a billion people globally [4, 5]. Here, we show that marine heatwave events on coral reefs are biologically distinct to how coral bleaching has been understood to date, in that heatwave conditions result in an immediate heat-induced mortality of the coral colony, rapid coral skeletal dissolution, and the loss of the three-dimensional reef structure. During heatwave-induced mortality, the coral skeletons exposed by tissue loss are, within days, encased by a complex biofilm of phototrophic microbes, whose metabolic activity accelerates calcium carbonate dissolution to rates exceeding accretion by healthy corals and far greater than has been documented on reefs under normal seawater conditions. This dissolution reduces the skeletal density and hardness and increases porosity. These results demonstrate that severe-heatwave-induced mortality events should be considered as a distinct biological phenomenon from bleaching events on coral reefs. We also suggest that such heatwave mortality events, and rapid reef decay, will become more frequent as the intensity of marine heatwaves increases and provides further compelling evidence for the need to mitigate climate change and instigate actions to reduce marine heatwaves.
Lohr, KE, Camp, EF, Kuzhiumparambil, U, Lutz, A, Leggat, W, Patterson, JT & Suggett, DJ 2019, 'Resolving coral photoacclimation dynamics through coupled photophysiological and metabolomic profiling.', The Journal of experimental biology, vol. 222, no. Pt 8.View/Download from: UTS OPUS or Publisher's site
Corals continuously adjust to short-term variation in light availability on shallow reefs. Long-term light alterations can also occur as a result of natural and anthropogenic stressors, as well as management interventions such as coral transplantation. Although short-term photophysiological responses are relatively well understood in corals, little information is available regarding photoacclimation dynamics over weeks of altered light availability. We coupled photophysiology and metabolomic profiling to explore changes that accompany longer-term photoacclimation in a key Great Barrier Reef coral species, Acropora muricata High light (HL)- and low light (LL)-acclimated corals were collected from the reef and reciprocally exposed to high and low light ex situ Rapid light curves using pulse-amplitude modulation (PAM) fluorometry revealed photophysiological acclimation of LL corals to HL and HL corals to LL within 21 days. A subset of colonies sampled at 7 and 21 days for untargeted LC-MS and GC-MS metabolomic profiling revealed metabolic reorganization before acclimation was detected using PAM fluorometry. Metabolomic shifts were more pronounced for LL to HL corals than for their HL to LL counterparts. Compounds driving metabolomic separation between HL-exposed and LL control colonies included amino acids, organic acids, fatty acids and sterols. Reduced glycerol and campesterol suggest decreased translocation of photosynthetic products from symbiont to host in LL to HL corals, with concurrent increases in fatty acid abundance indicating reliance on stored lipids for energy. We discuss how these data provide novel insight into environmental regulation of metabolism and implications for management strategies that drive rapid changes in light availability.
Pollier, J, Vancaester, E, Kuzhiumparambil, U, Vickers, CE, Vandepoele, K, Goossens, A & Fabris, M 2019, 'A widespread alternative squalene epoxidase participates in eukaryote steroid biosynthesis.', Nature Microbiology, vol. 4, pp. 226-233.View/Download from: UTS OPUS or Publisher's site
Steroids are essential triterpenoid molecules that are present in all eukaryotes and modulate the fluidity and flexibility of cell membranes. Steroids also serve as signalling molecules that are crucial for growth, development and differentiation of multicellular organisms1-3. The steroid biosynthetic pathway is highly conserved and is key in eukaryote evolution4-7. The flavoprotein squalene epoxidase (SQE) catalyses the first oxygenation reaction in this pathway and is rate limiting. However, despite its conservation in animals, plants and fungi, several phylogenetically widely distributed eukaryote genomes lack an SQE-encoding gene7,8. Here, we discovered and characterized an alternative SQE (AltSQE) belonging to the fatty acid hydroxylase superfamily. AltSQE was identified through screening of a gene library of the diatom Phaeodactylum tricornutum in a SQE-deficient yeast. In accordance with its divergent protein structure and need for cofactors, we found that AltSQE is insensitive to the conventional SQE inhibitor terbinafine. AltSQE is present in many eukaryotic lineages but is mutually exclusive with SQE and shows a patchy distribution within monophyletic clades. Our discovery provides an alternative element for the conserved steroid biosynthesis pathway, raises questions about eukaryote metabolic evolution and opens routes to develop selective SQE inhibitors to control hazardous organisms.
Baker, KG, Radford, DT, Evenhuis, C, Kuzhiumparam, U, Ralph, PJ & Doblin, MA 2018, 'Thermal niche evolution of functional traits in a tropical marine phototroph.', Journal of phycology, vol. 54, no. 6, pp. 799-810.View/Download from: UTS OPUS or Publisher's site
Land-based plants and ocean-dwelling microbial phototrophs known as phytoplankton, are together responsible for almost all global primary production. Habitat warming associated with anthropogenic climate change has detrimentally impacted marine primary production, with the effects observed on regional and global scales. In contrast to slower-growing higher plants, there is considerable potential for phytoplankton to evolve rapidly with changing environmental conditions. The energetic constraints associated with adaptation in phytoplankton are not yet understood, but are central to forecasting how global biogeochemical cycles respond to contemporary ocean change. Here, we demonstrate a number of potential trade-offs associated with high-temperature adaptation in a tropical microbial eukaryote, Amphidinium massartii (dinoflagellate). Most notably, the population became high-temperature specialized (higher fitness within a narrower thermal envelope and higher thermal optimum), and had a greater nutrient requirement for carbon, nitrogen and phosphorus. Evidently, the energetic constraints associated with living at elevated temperature alter competiveness along other environmental gradients. While high-temperature adaptation led to an irreversible change in biochemical composition (i.e., an increase in fatty acid saturation), the mechanisms underpinning thermal evolution in phytoplankton remain unclear, and will be crucial to understanding whether the trade-offs observed here are species-specific or are representative of the evolutionary constraints in all phytoplankton.
Zavřel, T, Szabó, M, Tamburic, B, Evenhuis, C, Kuzhiumparambil, U, Literáková, P, Larkum, AWD, Raven, JA, Červený, J & Ralph, PJ 2018, 'Effect of carbon limitation on photosynthetic electron transport in Nannochloropsis oculata.', Journal of photochemistry and photobiology. B, Biology, vol. 181, pp. 31-43.View/Download from: UTS OPUS or Publisher's site
This study describes the impacts of inorganic carbon limitation on the photosynthetic efficiency and operation of photosynthetic electron transport pathways in the biofuel-candidate microalga Nannochloropsis oculata. Using a combination of highly-controlled cultivation setup (photobioreactor), variable chlorophyll a fluorescence and transient spectroscopy methods (electrochromic shift (ECS) and P700 redox kinetics), we showed that net photosynthesis and effective quantum yield of Photosystem II (PSII) decreased in N. oculata under carbon limitation. This was accompanied by a transient increase in total proton motive force and energy-dependent non-photochemical quenching as well as slightly elevated respiration. On the other hand, under carbon limitation the rapid increase in proton motive force (PMF, estimated from the total ECS signal) was also accompanied by reduced conductivity of ATP synthase to protons (estimated from the rate of ECS decay in dark after actinic illumination). This indicates that the slow operation of ATP synthase results in the transient build-up of PMF, which leads to the activation of fast energy dissipation mechanisms such as energy-dependent non-photochemical quenching. N. oculata also increased content of lipids under carbon limitation, which compensated for reduced NAPDH consumption during decreased CO2 fixation. The integrated knowledge of the underlying energetic regulation of photosynthetic processes attained with a combination of biophysical methods may be used to identify photo-physiological signatures of the onset of carbon limitation in microalgal cultivation systems, as well as to potentially identify microalgal strains that can better acclimate to carbon limitation.
Bodachivskyi, I, Kuzhiumparambil, U & Williams, DBG 2018, 'Acid-Catalyzed Conversion of Carbohydrates into Value-Added Small Molecules in Aqueous Media and Ionic Liquids.', ChemSusChem, vol. 11.View/Download from: UTS OPUS or Publisher's site
Biomass is the only realistic major alternative source (to crude oil) of hydrocarbon substrates for the commercial synthesis of bulk and fine chemicals. Within biomass, terrestrial sources are the most accessible, and therein lignocellulosic materials are most abundant. Although lignin shows promise for the delivery of certain types of organic molecules, cellulose is a biopolymer with significant potential for conversion into high-volume and high-value chemicals. This review covers the acid-catalyzed conversion of lower value (poly)carbohydrates into valorized organic building-block chemicals (platform molecules). It focuses on those conversions performed in aqueous media or ionic liquids to provide the reader with a perspective on what can be considered a best case scenario, that is, that the overall process is as sustainable as possible.
Curson, ARJ, Williams, BT, Pinchbeck, BJ, Sims, LP, Martínez, AB, Rivera, PPL, Kumaresan, D, Mercadé, E, Spurgin, LG, Carrión, O, Moxon, S, Cattolico, RA, Kuzhiumparambil, U, Guagliardo, P, Clode, PL, Raina, J-B & Todd, JD 2018, 'DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton.', Nature microbiology, vol. 3, no. 4, pp. 430-439.View/Download from: UTS OPUS or Publisher's site
Dimethylsulfoniopropionate (DMSP) is a globally important organosulfur molecule and the major precursor for dimethyl sulfide. These compounds are important info-chemicals, key nutrients for marine microorganisms, and are involved in global sulfur cycling, atmospheric chemistry and cloud formation1-3. DMSP production was thought to be confined to eukaryotes, but heterotrophic bacteria can also produce DMSP through the pathway used by most phytoplankton 4 , and the DsyB enzyme catalysing the key step of this pathway in bacteria was recently identified 5 . However, eukaryotic phytoplankton probably produce most of Earth's DMSP, yet no DMSP biosynthesis genes have been identified in any such organisms. Here we identify functional dsyB homologues, termed DSYB, in many phytoplankton and corals. DSYB is a methylthiohydroxybutryate methyltransferase enzyme localized in the chloroplasts and mitochondria of the haptophyte Prymnesium parvum, and stable isotope tracking experiments support these organelles as sites of DMSP synthesis. DSYB transcription levels increased with DMSP concentrations in different phytoplankton and were indicative of intracellular DMSP. Identification of the eukaryotic DSYB sequences, along with bacterial dsyB, provides the first molecular tools to predict the relative contributions of eukaryotes and prokaryotes to global DMSP production. Furthermore, evolutionary analysis suggests that eukaryotic DSYB originated in bacteria and was passed to eukaryotes early in their evolution.
Davey, PA, Pernice, M, Ashworth, J, Kuzhiumparambil, U, Szabó, M, Dolferus, R & Ralph, PJ 2018, 'A new mechanistic understanding of light-limitation in the seagrass Zostera muelleri.', Marine Environmental Research, vol. 134, pp. 55-67.View/Download from: UTS OPUS or Publisher's site
In this study we investigated the effect of light-limitation (∼20 μmol photons m-2 s-1) on the southern hemisphere seagrass, Zostera muelleri. RNA sequencing, chlorophyll fluorometry and HPLC techniques were used to investigate how the leaf-specific transcriptome drives changes in photosynthesis and photo-pigments in Z. muelleri over 6 days. 1593 (7.51%) genes were differentially expressed on day 2 and 1481 (6.98%) genes were differentially expressed on day 6 of the experiment. Differential gene expression correlated with significant decreases in rETRMax, Ik, an increase in Yi (initial photosynthetic quantum yield of photosystem II), and significant changes in pigment composition. Regulation of carbohydrate metabolism was observed along with evidence that abscisic acid may serve a role in the low-light response of this seagrass. This study provides a novel understanding of how Z. muelleri responds to light-limitation in the marine water column and provides potential molecular markers for future conservation monitoring efforts.
Watanabe, S, Kuzhiumparambil, U & Fu, S 2018, 'In vitro metabolism of synthetic cannabinoid AM1220 by human liver microsomes and Cunninghamella elegans using liquid chromatography coupled with high resolution mass spectrometry', FORENSIC TOXICOLOGY, vol. 36, no. 2, pp. 435-446.View/Download from: UTS OPUS or Publisher's site
Watanabe, S, Kuzhiumparambil, U & Fu, S 2018, 'Structural Elucidation of Metabolites of Synthetic Cannabinoid UR-144 by Cunninghamella elegans Using Nuclear Magnetic Resonance (NMR) Spectroscopy.', The AAPS journal, vol. 20, no. 2.View/Download from: UTS OPUS or Publisher's site
The number of new psychoactive substances keeps on rising despite the controlling efforts by law enforcement. Although metabolism of the newly emerging drugs is continuously studied to keep up with the new additions, the exact structures of the metabolites are often not identified due to the insufficient sample quantities for techniques such as nuclear magnetic resonance (NMR) spectroscopy. The aim of the study was to characterise several metabolites of the synthetic cannabinoid (1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl) methanone (UR-144) by NMR spectroscopy after the incubation with the fungus Cunninghamella elegans. UR-144 was incubated with C. elegans for 72 h, and the resulting metabolites were chromatographically separated. Six fractions were collected and analysed by NMR spectroscopy. UR-144 was also incubated with human liver microsomes (HLM), and the liquid chromatography-high resolution mass spectrometry analysis was performed on the HLM metabolites with the characterised fungal metabolites as reference standards. Ten metabolites were characterised by NMR analysis including dihydroxy metabolites, carboxy and hydroxy metabolites, a hydroxy and ketone metabolite, and a carboxy and ketone metabolite. Of these metabolites, dihydroxy metabolite, carboxy and hydroxy metabolites, and a hydroxy and ketone metabolite were identified in HLM incubation. The results indicate that the fungus is capable of producing human-relevant metabolites including the exact isomers. The capacity of the fungus C. elegans to allow for NMR structural characterisation by enabling production of large amounts of metabolites makes it an ideal model to complement metabolism studies.
Morelato, M, Barash, M, Blanes, L, Chadwick, S, Dilag, J, Kuzhiumparambil, U, Nizio, KD, Spindler, X & Moret, S 2017, 'Forensic Science: Current State and Perspective by a Group of Early Career Researchers', Foundations of Science, vol. 22, no. 4, pp. 799-825.View/Download from: UTS OPUS or Publisher's site
Forensic science and its influence on policing and the criminal justice system have increased since the beginning of the twentieth century. While the philosophies of the forensic science pioneers remain the pillar of modern practice, rapid advances in technology and the underpinning sciences have seen an explosion in the number of disciplines and tools. Consequently, the way in which we exploit and interpret the remnant of criminal activity are adapting to this changing environment. In order to best exploit the trace, an interdisciplinary approach to both research and investigation is required. In this paper, nine postdoctoral research fellows from a multidisciplinary team discuss their vision for the future of forensic science at the crime scene, in the laboratory and beyond. This paper does not pretend to be exhaustive of all fields of forensic science, but describes a portion of the postdoctoral fellows' interests and skills.
Watanabe, S, Kuzhiumparambil, U, Nguyen, MA, Cameron, J & Fu, S 2017, 'Metabolic Profile of Synthetic Cannabinoids 5F-PB-22, PB-22, XLR-11 and UR-144 by Cunninghamella elegans.', The AAPS Journal, vol. 19, no. 4, pp. 1148-1162.View/Download from: UTS OPUS or Publisher's site
The knowledge of metabolic profile of synthetic cannabinoids is important for the detection of drugs in urinalysis due to the typical absence or low abundance of parent cannabinoids in human urine. The fungus Cunninghamella elegans has been reported to be a useful tool for metabolism study and thus applicability to synthetic cannabinoid metabolism was examined. In this study, 8-quinolinyl 1-(5-fluoropentyl)-1H-indole-3-carboxylate (5F-PB-22), 8-quinolinyl 1-pentyl-1H-indole-3-carboxylate (PB-22), [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11) and (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144) were incubated with C. elegans and the metabolites were identified using liquid chromatography-quadrupole time-of-flight mass spectrometry. The obtained metabolites were compared with reported human metabolites to assess the suitability of the fungus to extrapolate human metabolism. 5F-PB-22 underwent dihydroxylation, dihydrodiol formation, oxidative defluorination, oxidative defluorination to carboxylic acid, ester hydrolysis and glucosidation, alone and/or in combination. The metabolites of PB-22 were generated by hydroxylation, dihydroxylation, trihydroxylation, dihydrodiol formation, ketone formation, carboxylation, ester hydrolysis and glucosidation, alone and/or in combination. XLR-11 was transformed through hydroxylation, dihydroxylation, aldehyde formation, carboxylation, oxidative defluorination, oxidative defluorination to carboxylic acid and glucosidation, alone and/or in combination. UR-144 was metabolised by hydroxylation, dihydroxylation, trihydroxylation, aldehyde formation, ketone formation, carboxylation, N-dealkylation and combinations. These findings were consistent with previously reported human metabolism except for the small extent of ester hydrolysis observed and the absence of glucuronidation. Despite the limitations, C. elegans demonstrated the capacity to produce a wide variety of met...
Yan, J, Kuzhiumparambil, U, Bandodkar, S, Solowij, N & Fu, S 2017, 'Development and validation of a simple, rapid and sensitive LC-MS/MS method for the measurement of urinary neurotransmitters and their metabolites', ANALYTICAL AND BIOANALYTICAL CHEMISTRY, vol. 409, no. 30, pp. 7191-7199.View/Download from: UTS OPUS or Publisher's site
Koyyalamudi, SR, Kuzhiumparambil, U, Nath, CE, Byrne, JA, Fraser, CJ, O'Brien, TA, Earl, JW & Shaw, PJ 2016, 'Development and Validation of a High Pressure Liquid Chromatography-UV Method for the Determination of Treosulfan and Its Epoxy Metabolites in Human Plasma and Its Application in Pharmacokinetic Studies', JOURNAL OF CHROMATOGRAPHIC SCIENCE, vol. 54, no. 3, pp. 326-333.View/Download from: UTS OPUS or Publisher's site
Kumar, M, Kuzhiumparambil, U, Pernice, M, Jiang, Z & Ralph, PJ 2016, 'Metabolomics: an emerging frontier of systems biology in marine macrophytes', ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS, vol. 16, pp. 76-92.View/Download from: UTS OPUS or Publisher's site
Watanabe, S, Kuzhiumparambil, U, Winiarski, Z & Fu, S 2016, 'Biotransformation of synthetic cannabinoids JWH-018, JWH-073 and AM2201 by Cunninghamella elegans', Forensic Science International, vol. 261, pp. 33-42.View/Download from: UTS OPUS or Publisher's site
Being marketed as 'legal' smoking blends or mixtures, synthetic cannabinoids are abused widely owing to its cannabis-like effect. Due to the rapid introduction of new generation analogues of synthetic cannabinoids to escape from legislative/judicial control, the investigation of the metabolic pathways of these substances is of particular importance for drug control, abstinence and forensic toxicology purposes. In this study, the in vitro metabolism of JWH-018, JWH-073 and AM2201 by the fungus Cunninghamella elagans has been investigated with the purpose of validating its potential as a complementary model for investigating synthetic cannabinoid metabolism. JWH-018, JWH-073 and AM2201 were incubated for 72 h with C. elegans. Detection of metabolites was based on liquid chromatography–tandem mass spectrometry and high resolution mass spectrometry analysis. C. elegans was found capable of producing the majority of the phase I metabolites observed in earlier in vitro and in vivo mammalian studies as a result of monohydroxylation, dihydroxylation, carboxylation, dehydrogenation, ketone formation, dihydrodiol formation, dihydrodiol formation with N-dealkylation and combinations thereof. C. elegans can thus be a useful and economic model for studying synthetic cannabinoid metabolism.
Watanabe, S, Kuzhiumparambil, U, Winiarski, Z & Fu, S 2016, 'Data on individual metabolites of synthetic cannabinoids JWH-018, JWH-073 and AM2201 by Cunninghamella elegans', Data in Brief, vol. 7, pp. 332-340.View/Download from: UTS OPUS or Publisher's site
Synthetic cannabinoids JWH-018, JWH-073 and AM2201 were metabolised by the fungus Cunninghamella elegans. In this article, data on individual metabolites of their retention times, mass accuracies, major product ions and structures indicated by product ions are presented. The data in this article is related to 'Biotransformation of synthetic cannabinoids JWH-018, JWH-073 and AM2201 by Cunninghamella elegans'
Kuzhiumparambil, U, Watanabe, S & Fu, S 2015, 'Oxidation of testosterone by permanganate and its implication in sports drug testing', NEW JOURNAL OF CHEMISTRY, vol. 39, no. 3, pp. 1597-1602.View/Download from: UTS OPUS or Publisher's site
Luong, S, Kuzhiumparambil, U & Fu, S 2015, 'Elucidation of markers for monitoring morphine and its analogs in urine adulterated with pyridinium chlorochromate.', Bioanalysis, vol. 7, no. 18.View/Download from: UTS OPUS or Publisher's site
Currently, procedures that identify the drugs 'destroyed' in adulterated urine specimens are very limited. This study aimed to determine the effect of pyridinium chlorochromate (PCC) on routine opiate assays and identify reaction products formed. Results/methodology: Opiate-positive urines adulterated with PCC (20 and 100 mM) were analyzed using CEDIA(®) immunoassay and GC-MS. Urine and water samples spiked with 6-monoacetylmorphine, morphine and its glucuronides (10 µg/ml) and PCC (0.02-100 mM) were monitored with LC-MS, and the products characterized.PCC significantly decreased the abundance of morphine, codeine and IS. Adulterated water and urine samples containing 6-monoacetylmorphine, morphine and morphine-3-glucuronide yielded morphinone-3-glucuronide, 7,14-dihydroxy-6-monoacetylmorphine, 7,8-diketo-6-monoacetylmorphine and 7,8-diketo-morphine (tentative assignment). Reaction pathways may be different in the two matrices.
Szabo, M, Parker, KB, Guruprasad, S, Kuzhiumparambil, U, Lilley, RM, Tamburic, B, Schliep, MT, Larkum, A, Schreiber, U, Raven, J & Ralph, PJ 2014, 'Photosynthetic acclimation of Nannochloropsis oculata investigated by multi-wavelength chlorophyll fluorescence analysis', Bioresource Technology, vol. 167, pp. 521-529.View/Download from: UTS OPUS or Publisher's site
Multi-wavelength chlorophyll fluorescence analysis was utilised to examine the photosynthetic efficiency of the biofuel-producing alga Nannochloropsis oculata, grown under two light regimes; low (LL) and high (HL) irradiance levels. Wavelength dependency was evident in the functional absorption cross-section of Photosystem II (sII (?)), absolute electron transfer rates (ETR(II)), and non-photochemical quenching (NPQ) of chlorophyll fluorescence in both HL and LL cells. While sII(?) was not significantly different between the two growth conditions, HL cells upregulated ETR(II) 1.6 to 1.8-fold compared to LL cells, most significantly in the wavelength range of 440-540 nm. This indicates preferential utilisation of blue-green light, a highly relevant spectral region for visible light in algal pond conditions. Under these conditions, the HL cells accumulated saturated fatty acids, whereas polyunsaturated fatty acids were more abundant in LL cells. This knowledge is of importance for the use of N. oculata for fatty acid production in the biofuel industry.
Fu, S, Luong, S, Pham, A, Charlton, N & Kuzhiumparambil, U 2014, 'Bioanalysis of urine samples after manipulation by oxidizing chemicals: technical considerations', BIOANALYSIS, vol. 6, no. 11, pp. 1543-1561.View/Download from: Publisher's site
Ung, AT, Williams, SG, Angeloski, A, Ashmore, J, Kuzhiumparambil, U, Bhadbhade, M & Bishop, R 2014, 'Formation of 3-azabicyclo[3.3.1]non-3-enes: imino amides vs. imino alkenes', Monatshefte fur Chemie, vol. 145, no. 6, pp. 983-992.View/Download from: UTS OPUS or Publisher's site
An effective method for synthesising alkaloidlike compounds containing the 3-azabicyclo[3.3.1]non-3-ene core structure was successfully carried out in a stereoselective manner via the bridged-Ritter reactions. Important optically active 6-alkyl(aryl)amido-4-alkyl( aryl)-2,2,6-trimethyl-3-azabicyclo[3.3.1]non-3-enes (imino amides) and 4-alkyl(aryl)-2,2,6-trimethyl-3-azabicyclo[3.3.1]nona-3,6-dienes (imino alkenes) were obtained in one step from (-)-b-pinene and the respective nitriles in the presence of concentrated H2SO4. The relative compositions of these products were controlled by varying the reaction conditions. Kinetic studies were conducted to enable a mechanistic understanding of the reaction pathways.
Kuzhiumparambil, U & Fu, S 2013, 'Effect of hydrogen peroxide oxidation systems on human urinary steroid profiles', Analytical Methods, vol. 5, no. 17, pp. 4402-4408.View/Download from: UTS OPUS or Publisher's site
In sports drug testing the steroid profile is the most versatile and informative screening tool for the detection of steroid abuse. Despite the introduction of observed urine collection procedures by the World Anti-Doping Agency (WADA), chemical manipulation of urine specimens by athletes to conceal drug use still occurs and poses an ongoing challenge for doping control laboratories worldwide. In vitro urine adulteration using highly oxidative chemicals have been reported several times in the past. In this study we report the effect of two oxidising agents, Fenton's reagent and peroxidaseperoxide system on the human urinary steroid profile. Varying concentrations of these oxidants were reacted with urine and the reactions monitored by gas chromatography-mass spectrometry. A significant decrease in the absolute concentrations of androsterone, etiocholanolone, 5a-androstane-3a,17ß-diol, 5ß-androstane-3a,17ß-diol and epitestosterone was observed with consequent alteration of the steroid profile ratios. Adulteration of urine sample with these oxidants can thus mask the abnormality in a steroidal profile following steroid abuse. Drug testing authorities should take into account the effects of these oxidizing adulterants while interpreting the steroid profile data for doping control purposes.
Steroid profiling is the most versatile and informative technique adapted by doping control laboratories for detection of steroid abuse. The absolute concentrations and ratios of endogenous steroids including testosterone, epitestosterone, androsterone, etiocholanolone, 5a-androstane-3a,17ß-diol and 5ß-androstane-3a,17ß-diol constitute the significant characteristics of a steroid profile. In the present study we report the influence of various oxidizing adulterants on the steroid profile of human urine. Gas chromatographymass spectrometry analysis was carried out to develop the steroid profile of human male and female urine. Oxidants potassium nitrite, sodium hypochlorite, potassium permanganate, cerium ammonium nitrate, sodium metaperiodate, pyridinium chlorochromate, potassium dichromate and potassium perchlorate were reacted with urine at various concentrations and conditions and the effect of these oxidants on the steroid profile were analyzed. Most of the oxidizing chemicals led to significant changes in endogenous steroid profile parameters which were considered stable under normal conditions. These oxidizing chemicals can cause serious problems regarding the interpretation of steroid profiles and have the potential to act as masking agents that can complicate or prevent the detection of the steroid abuse
Raghu, AV, Unnikrishnan, K, Geetha, SP, Martin, G & Balachandran, I 2011, 'Plant regeneration and production of embelin from organogenic and embryogenic callus cultures of Embelia ribes Burm. f.-a vulnerable medicinal plant', IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-PLANT, vol. 47, no. 4, pp. 506-515.View/Download from: UTS OPUS or Publisher's site
Perinchery, SM, Kuzhiumparambil, U, Vemulpad, S & Goldys, EM 2010, 'The influence of indoxyl sulfate and ammonium on the autofluorescence of human urine', TALANTA, vol. 80, no. 3, pp. 1269-1276.View/Download from: Publisher's site
Perinchery, SM, Kuzhiumparambil, U, Vemulpad, S & Goldys, EM 2010, 'The potential of autofluorescence spectroscopy to detect human urinary tract infection', TALANTA, vol. 82, no. 3, pp. 912-917.View/Download from: Publisher's site
George, S, Tushar, KV, Unnikrishnan, KP, Hashim, KM & Balachandran, I 2008, 'Hemidesmus indicus (L.) R. Br. A review', Journal of Plant Sciences, vol. 3, no. 2, pp. 146-156.View/Download from: Publisher's site
Hemidesmus indicus (L.) R. Br. (Periplocaceae) is being used widely in Ayurvedic medicine. The history of its medicinal importance dates back to ancient times. The present review deals with studies undertaken in various aspects of this plant in the areas of morphology, anatomy, pharmacology, chemistry and ethnobotany along with medicinal uses. © 2008 Academic Journals Inc.
Srinivasan, GV, Unnikrishnan, KP, Shree, ABR & Balachandran, I 2008, 'HPLC Estimation of berberine in Tinospora cordifolia and Tinospora sinensis', INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 70, no. 1, pp. 96-U21.View/Download from: Publisher's site
Sudhakar Raja, S, Unnikrishnan, KP, George, S, Remashree, AB, Udayan, PS, Tushar, KV & Balachandran, I 2008, 'Variation in vasicine content and pharmacognostic characters of morphotypes of Adhatoda zeylanica Medic', Journal of Plant Sciences, vol. 3, no. 1, pp. 61-68.View/Download from: Publisher's site
As part of the gene bank activity of CMPR many collections of Adhatoda zeylanica Medic. were made from varying agroecological regions in South India. These collections could be grouped into four morphotypes based on growth habits and other morphological characters. These four morphotypes were evaluated for their chemical and pharmacognostical characters and significant differences among the morphotypes were noticed. Among quality characters vasicine content, fingerprint profiles, stomatal index, leaf architecture and venation pattern showed significant variation indicating the predominance of additive gene effects. A reverse phase HPLC method for the quantitative determination of vasicine in the morphotypes was developed based on which variation in the vasicine content was observed. Thin layer chromatographic analysis showed variation in the chemical composition of these morphotypes. These studies indicated variability in the chemical composition and pharmacognostic characters among the morphotypes of A. zeylanica. Two of the morphotypes containing significantly higher vasicine indicated the presence of chemical diversity, providing adequate scope for selection of superior chemotypes having high therapeutic value and economic benefit. © 2008 Academic Journals Inc.
Unnikrishnan, KP, Raja, SS & Balachandran, I 2008, 'A Reverse Phase HPLC-UV and HPTLC Methods for Determination of Plumbagin in Plumbago indica and Plumbago zeylanica', INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 70, no. 6, pp. 844-847.View/Download from: Publisher's site
., AVR, ., KPU, ., KMH, ., IB & ., KVM 2007, 'Studies on Morphological and Phytochemical Variability of Different Populations of Tribulus terrestris', International Journal of Plant Breeding and Genetics, vol. 1, no. 2, pp. 95-100.View/Download from: Publisher's site
Unnikrishnan, KP, Fathima, A, Hashim, KM & Balachandran, I 2007, 'Antioxidant studies and determination of wedelolactone in Eclipta alba', Journal of Plant Sciences, vol. 2, no. 4, pp. 459-464.View/Download from: Publisher's site
The present research reports the results of the phytochemical studies carried out to identify the diagnostic features of the E. alba. A high performance thin layer chromatographic method was standardized to determine the wedelolactone content in whole plant of E. alba. Methanolic extracts of samples from three different sources were used for analysis. The mean assay of wedelolactone was of range 0.481-0.702 mg g-1 of drug powder. Radical scavenging activity of methanolic extract was evaluated by DPPH assay method superoxide radical scavenging activity in riboflavin/light/NBT system and nitric oxide radical scavenging activity in sodium nitroprusside/Griess reagent system. The assay results indicate that the DPPH, superoxide and nitric oxide scavenging activity were intense (19.25, 39.25 and 58.26 μg mL-1, respectively). The phytochemical features identified in the present study can be used as identification markers of this important analgesic agent. © 2007 Academic Journals Inc.
Kumar, M, Ralph, P & Kuzhiumparambil, U 2017, 'Polyamines-stress metabolites in marine macrophytes' in ALGAL GREEN CHEMISTRY: RECENT PROGRESS IN BIOTECHNOLOGY, Elsevier.View/Download from: UTS OPUS or Publisher's site
Kuzhiumparambil, U, Kumar, M & Ralph, P 2017, 'Gas and liquid chromatography-mass spectrometry-based metabolic profiling of marine angiosperm Zostera Muelleri (alismatales, zosteraceae)' in Systems Biology of Marine Ecosystems, pp. 189-203.View/Download from: UTS OPUS or Publisher's site
© Springer International Publishing AG 2017. Seagrasses are monocotyledonous marine flowering plants that are considered lungs of the sea and are the most intense carbon sinks on the planet, delivering a range of ecologically and economically valuable biological services. In this study, we report the chemical fingerprint of Zostera muelleri using an untargeted metabolomic approach. High-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS) were performed to study the metabolic profile of Z. muelleri. A total of 98 metabolites belonging to various chemical classes including flavonoids, phenolics, lipids, fatty acids, sugar alcohols and amino acids were identified, including two characteristic marker compounds of the genus, zosteric acid and rosmarinic acid. Chromatographic profiling yield a comprehensive map for the chemical constituents of Z. muelleri, and this method can be used as an effective and convenient approach to gain insights into the chemical composition of other seagrasses.
Verma, A, Kohli, G, Hoppenrath, M, Harwood, T, Kuzhiumparambil, U, Ralph, P & Murray, S 2016, 'Systematics and diversity of the genus Ostreopsis in the East Australian Current region', Marine and Fresh-Water Harmful Algae. Proceedings of the 17th International Conference on Harmful Algae., International Conference on Harmful Algae, International Society for Study of Harmful Algae, Brazil, pp. 84-88.View/Download from: UTS OPUS