Current research in my group
Methylated amines and nitrogenous osmolytes: We have pioneered in the understanding of novel metabolic pathways and new enzymes leading to the re-mineralization of ammonium from organic nitrogen species, particularly methylated amines, in the surface marine waters. Our work has improved understanding of the role of key cosmopolitan marine heterotrophic bacteria, such as the Roseobacter clade and the marine SAR11 clade in ammonium re-mineralization (Chen et al., PNAS, 2011; Lidbury et al., PNAS, 2014).
Microbial interactions, cell surface and membrane lipids in the stress and nutrient limitation response. We recently demonstrated that marine heterotrophic bacteria can remodel their lipid composition in response to nutrient limitation (e.g. phosphorus) (Sebastian et al., 2016, The ISME Journal). Key to the lipid remodelling process in these marine heterotrophs is a novel intracellular phospholipase C, which is particularly abundant in natural marine bacterial communities, especially in areas characterised by low phosphate concentrations. We have recently characterised a novel pathway leading to the formation of these unique aminolipids in marine bacteria (Smith et al., 2019 The ISME Journal; Smith et al., 2021 The ISME Journal). These results pointed to the previously overlooked key role of lipid substitution as an adaptive strategy, enabling heterotrophs to thrive in the vast phosphorus-depleted areas of the oceans and resolved the paradox of SAR11-phytoplankton competition in oligotrophic oceans. Such a membrane remodelling strategy also comes with unforeseen ecophysiological consequences in trade-offs of certain traits (e.g. Guillonneau et al., 2022 PNAS). In parallel, we also begin to understand the role of lipid remodelling in bacterial pathogens, some of which can substitute membrane lipids in order to become resistant to antibiotics (e.g. Jones et al., 2021 The ISME Journal; Shropshire et al., 2023).
Interplay of diet, gut microbiota and host health and disease. We are particularly interested in understanding the role of quaternary amine metabolism and methylated amine formation in human gut. In the study published in 2014, we have identified a novel Rieske-containing oxygenase involved in gut microbial catabolism of carnitine to trimethylamine (Zhu et al., 2014 PNAS). We recently solved the structure of this key enzyme CntA (Quareshy et al., 2021 J Biol Chem), help us better understand the mechanisms responsible (Shanmugam et al., 2021 Angewandte Chemie) for carnitine degradation by gut microbiota, providing a reliable biomarker for investigating key gut microbes involved in carnitine-diet induced cardiovascular diseases.