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Title: Functional genomics of methylated sulfur compound metabolism in Hyphomicrobium species
Author: Fetherston, Richard
ISNI:       0000 0004 8497 8793
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2018
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Methylated sulfur compounds (MSCs) are a group of organosulfur compounds with various roles in agriculture, industry, medicine and the biogeochemical sulfur cycle, making their microbial metabolism an important area of study. The overarching aim of this project has been to investigate the molecular mechanisms allowing bacterial species to metabolise MSCs by studying members of the methylotrophic Hyphomicrobium genus - namely Hyphomicrobium denitrificans ATCC51888, Hyphomicrobium methylovorum Bras1 and Hyphomicrobium sulfonivorans S1 - using a combination of genetics, genomics, proteomics and transcriptomics. These model Alphaprotoebacteria can utilise MSCs such as dimethylsuilfide (DMS), dimethylsulfoxide (DMSO), dimethylsulfone (DMSO2), methanesulfonic acid (MSA) and methanethiol (MT) as a sole source of carbon, sulfur and/or energy. At the project's outset the mechanism Hyphomicrobium species use to degrade MSCs was thought largely understood, following the characterisation of a DMS oxidising DmoABtype DMS monooxygenase from Hyphomicrobium sulfonivorans S1 and a MT oxidising MtoX-type MT oxidase from Hyphomicrobium sp. VS, leading to the suggestion that Hyphomicrobium species first reduce DMSO2 and DMSO to DMS, then oxidise that DMS to hydrogen sulfide and formaldehyde via a MT intermediate. However, this study now indicates that Hyphomicrobium species actually contain two distinct pathways of methylotrophic MSC metabolism. The first is a putative DMSO2 oxidation pathway - proposed to contain the DmoAB and an SfnFG-type DMSO2 monooxygenase - that generates formaldehyde and sulfite via the intermediate MSA leading to sulfite adenylylation for sulfur excretion. The second is a putative DMS oxidation pathway - proposed to contain MtoX and an as yet-unidentified DMS oxidising enzyme - that generates and formaldehyde and hydrogen sulfite via a MT intermediate leading to thiosulfate oxidation via the SOX system. Furthermore, this study identifies an additional non-methyltrophic DMSO2 oxidation pathway in H. sulfonivorans that is specifically induced in response to sulfur starvation and capable of utilising DMSO2, DMSO, DMS and MSA as a sole sulfur source, even in the absence of a functional DmoAB-type DMS monooxygenase.
Supervisor: Not available Sponsor: Natural Environment Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry ; QR Microbiology