Microbial metabolism of methylamines & methylated sulfurs 

Quaternary amines (QAs) such as glycine betaine (GBT) are ubiquitous in marine organisms. GBT is used by marine organisms as a compatible solute in response to changes in environmental conditions, such as increasing salinity, because GBT does not interfere with cell metabolism. QA compounds are frequently released into the ocean ecosystems due to environmental changes, such as viral attack and grazing. The degradation of these compounds, especially in intertidal coastal areas, contributes significantly to the production of climate-active trace gases. These include the potent greenhouse gas methane and volatile methylated amines, which are thought to be involved in cloud formation in the marine environment.

Coastal sediments are estimated to contribute approximately 75% of the global oceanic methane emissions (8-13 Tg per year) and much of this is likely to be derived from the degradation of QAs. Although we know that microorganisms are mainly responsible for the degradation of GBT to methane and volatile methylamines, we know little about the genes and enzymes involved in the degradation pathway. Furthermore, the identity of those microorganisms responsible for the transformation has not yet been determined. Our current knowledge of these two aspects remains speculative, at least partially due to the lack of definitive research.

This NERC-funded project (2012-2016) aims to fill in this major gap in our knowledge of marine carbon cycle. Using cultivated model microorganisms, we aim to define the key genes and the encoding enzymes in the anaerobic degradation of GBT. Using molecular ecology techniques and the resultant data from the study of the model microorganisms, we aim to further determine the key microbial players involved in the anaerobic production of methane and methylamines from GBT in the marine environment.

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Project investigators: PI Y Chen

CoI Dr R Airs (Plymouth Marine Laboratory). DJ Scanlan (Warwick), K Purdy (Warwick)

Methylamines represent a major group of metabolites in human gut. Microbial transformation of dietary precursors to methylated amines is implicated in the development of several human disorders, including insulin resistance, liver disease and cardiovascular diseases. We have continued interest in understanding the transformation of methylamines in gut microbiota. Our group has recently characterized a novel microbial pathway leading to the formation of trimethylamine from dietary carnitine from gut microbiota (Zhu et al., 2014 PNAS). We have also recently shown that trimethylamine formation from choline degradation leads to enhanced growth and swarming of Proteus mirabilis (Jameson et al, 2015 Environ Microbiol).

Postdoctoral research fellow: Dr Mussa Quareshy, funded by Leverhulme Trust.

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 Project investigators: Dr Yin Chen (University of Warwick), Prof A Cameron (University of Warwick), Prof T Bugg (University of Warwick)

• Wang N, Chen XL, Gao C, Peng M, Wang P, Zhang N, Li FC, Yang GP, Shen QT, Chen Y, Zhang YZ, Li CY (2021) Crystal structure of gamma-glytamylmethylamide synthetase provide insight into bacterial metabolism of oceanic monomethylamine. J Biol Chem in press 

• Shanmugam M, Quareshy M, Cameron AD, Bugg TDH, Chen Y (2021). Light-Activated Electron Transfer and Catalytic Mechanism of Carnitine Oxidation by Rieske-type Oxygenase from Human Microbiota, Angewandte Chemie 60, 4529 – 4534 

• Quareshy M, Shanmugam M, Townsend E, Jameson E, Bugg TDH, Cameron AD, Chen Y (2021). Structural basis of carnitine monooxygenase CntA substrate specificity, inhibition and inter-subunit electron transfer. J Biol Chem. in press 

• E Jameson, J Stephenson, H Jones, A Millard, AK Kaster, KJ Purdy, R Airs, JC Murrell, Y Chen*. (2018) Deltaproteobacteria (Pelobacter) and Methanococcides are responsible for choline-dependent methanogenesis in a coastal saltmarsh sediment. ISME Journal, in press.

• Lidbury I1, Mausz M1, Scanlan DJ, Chen Y*. (2017) Identification of dimethylamine monooxygenase in marine bacteria reveals a metabolic bottleneck in the marine methylated amine degradation pathway.(1equal contribution). The ISME Journal, 11: 1592-1601.

• M Taubert, C Grob, AM Howat, OJ Burns, J Pratscher, N Jehmlich, M von Bergen, HH Richnow, Y Chen*, JC Murrell *(2017) Methylamine as a Nitrogen Source for Microorganisms from a Coastal Marine Environment Environmental Microbiology, 19(6): 2246–2257.

• CY Li, XL Chen, D Zhang, P Wang, Q Sheng, M Peng, BB Xie, QL Qin, PY Li, XY Zhang, HN Su, XY Song, M Shi, BC Zhou, LY Xun, Y Chen, YZ Zhang (2017) Structural mechanisms for bacterial oxidation of oceanic trimethylamine into trimethylamine N-oxide. Molecular Microbiology 103:992–1003.

• Zhu Y, Ksibe AZ, Schäfer H, Blindauer CA, Bugg TDH, Chen Y*. (2016) O2-independent demethylation of trimethylamine N-oxide by Tdm of Methylocella silvestris. The FEBS Journal. 283: 3979–3993.

• Jameson E, Doxey AC, Airs R, Purdy KJ, Murrell JC, Chen Y*. (2016) Metagenomic data-mining reveals contrasting microbial populations responsible for trimethylamine formation in human gut and marine ecosystems Jameson E, Fu T, Brown IR,Paszkiewicz K, Purdy KJ, Frank S, Chen Y. (2015) Anaerobic choline metabolism in microcompartments promotes growth and swarming of Proteus mirabilis. Environmental Microbiology, in press.

• Zhu, Y., Jameson, E., Crosatti, M., Schafer, H., Rajakumar, K., Bugg, T.D.H., Chen., Y (2014) 'Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota', Proceedings Of The National Academy Of Sciences (USA), 111 (11), 4268 - 4273.

• Y Zhu, E Jameson, R A Parslow, I Lidbury, T Fu, T R Dafforn, H Schafer, Y Chen (2014) 'Identification and characterization of trimethylamine N-oxide (TMAO) demethylase and TMAO permease in Methylocella silvestris BL2', Environmental Microbiology, 16 (10), 3318 - 3330.

• Lidbury, I., Murrell, J.C., Chen, Y. (2014) 'Trimethylamine N-oxide metabolism by abundant marine heterotrophic bacteria', Proceedings Of The National Academy Of Sciences (USA), 111 (7), 2710 - 2715

• Lidbury, I. Murrell, J.C., Chen, Y. (2014) 'Trimethylamine and trimethylamine N-oxide are supplementary energy sources for a marine heterotrophic bacterium: implications for marine carbon and nitrogen cycling', ISME Journal, in press

Microbial degradation of DMS/DMSO/DMSP in the marine environment

We are collaborating with Prof Hendrik Schafer (University of Warwick), Prof J Todd (University of East Anglia), Dr Ozge Eyice-Broadbent (Queen Mary University, London) and Profs Yu-zhong Zhang & Chuyang Li (Ocean University of China) on several NERC-funded projects, investigating the role of marine microbes in methylated sulfur metabolism and the interplay between methylamines and DMS/P/O. 

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Postdoctoral research fellows: Dr Jess Palmer; Dr Alison Webb; Dr Jason Stephenson.

• Ubiquitous occurrence of a dimethylsulfoniopropionate ABC transporter in abundant marine bacteria. Li CY, Mausz MA, Murphy A, Zhang N, Chen XL, Wang SY, Gao C, Aguilo-Ferretjans MM, Silvano E, Lidbury IDEA, Fu HH, Todd JD, Chen Y, Zhang YZ. ISME J. 2023 Apr;17(4):579-587. doi: 10.1038/s41396-023-01375-3.

• Acrylate protects a marine bacterium from grazing by a ciliate predator. Teng ZJ, Wang P, Chen XL, Guillonneau R, Li CY, Zou SB, Gong J, Xu KW, Han L, Wang C, Scanlan DJ, Chen Y, Zhang YZ. Nat Microbiol. 2021 Nov;6(11):1351-1356. doi: 10.1038/s41564-021-00981-1.

• Biogeographic traits of dimethyl sulfide and dimethylsulfoniopropionate cycling in polar oceans. Teng ZJ, Qin QL, Zhang W, Li J, Fu HH, Wang P, Lan M, Luo G, He J, McMinn A, Wang M, Chen XL, Zhang YZ, Chen Y, Li CY. Microbiome. 2021 Oct 16;9(1):207. doi: 10.1186/s40168-021-01153-3.

• Structural and Mechanistic Insights Into Dimethylsulfoxide Formation Through Dimethylsulfide Oxidation. Wang XJ, Zhang N, Teng ZJ, Wang P, Zhang WP, Chen XL, Zhang YZ, Chen Y, Fu HH, Li CY. Front Microbiol. 2021 Sep 24;12:735793. doi: 10.3389/fmicb.2021.735793.

• A novel ATP dependent dimethylsulfoniopropionate lyase in bacteria that releases dimethyl sulfide and acryloyl-CoA. Li CY, Wang XJ, Chen XL, Sheng Q, Zhang S, Wang P, Quareshy M, Rihtman B, Shao X, Gao C, Li F, Li S, Zhang W, Zhang XH, Yang GP, Todd JD, Chen Y, Zhang YZ. Elife. 2021 May 10;10:e64045. doi: 10.7554/eLife.64045.

• Towards a systematic understanding of structure-function relationship of dimethylsulfoniopropionate-catabolizing enzymes. Chen Y, Schäfer H. Mol Microbiol. 2019 Jun;111(6):1399-1403. doi: 10.1111/mmi.14230. 

• A mechanism for bacterial transformation of dimethylsulfide to dimethylsulfoxide: a missing link in the marine organic sulfur cycle. Lidbury I, Kröber E, Zhang Z, Zhu Y, Murrell JC, Chen Y, Schäfer H. Environ Microbiol. 2016 Sep;18(8):2754-66. doi: 10.1111/1462-2920.13354.  

• SIP metagenomics identifies uncultivated Methylophilaceae as dimethylsulphide degrading bacteria in soil and lake sediment. Eyice Ö, Namura M, Chen Y, Mead A, Samavedam S, Schäfer H. ISME J. 2015 Nov;9(11):2336-48. doi: 10.1038/ismej.2015.37.