Award details

Exploring New Pathways of Sulfoquinovose degradation in the biosphere

Reference	BB/W003805/1
Principal Investigator / Supervisor	Professor Gideon Davies
Co-Investigators / Co-Supervisors	Dr Mahima Sharma
Institution	University of York
Department	Chemistry
Funding type	Research
Value (£)	469,673
Status	Current
Type	Research Grant
Start date	01/05/2022
End date	30/04/2025
Duration	36 months

Abstract

Approximately half of all biologically-available sulfur is estimated to be derived from an unusual plant sulfo-glycolipid, Sulfoquinovose diacylglycerol (SQDG), found within the thylakoid membranes of photosynthetic plants and bacteria. The metabolism and catabolism of the sulfonated carbohydrate Sulfoquinovose (SQ) is therefore crucial to the global carbon cycle, reflected in the 10 billion tonnes produced annually. The last 5-6 years has seen a great interest in how SQ is broken down (initially through Sulfo-Entner-Doudoroff [Sulfo-ED and Sulfo-Embden-Meyerhof-Parnas pathways) -with key questions around what pathways exist, using which chemistries and in what organisms and biological milieu are they found. Building on a substantial body of preliminary data, this grant will probe different SQ utilisation pathways. Work funded by the grant will analyse, at biochemical and structural levels, the key components of four SQ utilisation and breakdown pathways: Sulfo-ED, two pathways involving unusual and distinct aldolase steps, and an, as yet undescribed oxidative pathway Sulfo-Ox. Following the establishment of robust kinetic assays, the key mechanistic steps and crucial sulfonate head group recognition will be probed at the 3-D structural level. Analysis of sulfonate recognition motifs will enable further bioinformatics analysis of pathways in new organisms. Augmenting the pathway discovery, application of a newly discovered activity-based probe (in biotin and fluorescent versions) will allow us to study the SQ conditional expression of dissecting pathways, as well as discover new enzymes and novel pathways from environmental isolates. Overall the goal is to put sulfur acquisition from SQ on the same footing as the well characterised metabolism of the amino acids cysteine and methionine.

Summary

We all need sulfur. Sulfur is an important macronutrient for all living organisms. It is all around us, we consume about 0.2g a day, but how is it metabolised? How do bacteria convert the billions of tonnes of sulphur found in green leafy plants in the form of sulfur-containing lipids? Sulfoglycolipid study is still in its infancy, with novel pathways reported each year. Given its unusual chemical structure, organisms recruit specific transport and catalytic machinery to utilise this sulfosugar as energy source. This grant will study biodegradation and circulation of a major organosulfur resource within the biogeochemical sulfur cycle - one that reflects 50% of all biological sulfur yet very little is known about. The metabolism of this reservoir of biological sulfur - Sulfoquinovose SQ - is therefore far more complex and diverse than originally envisaged, yet, despite the massive quantity and fundamental importance of SQ, it remains a poorly understood area. We therefore seek to build upon our substantial preliminary data, to dissect these new pathways, produce tools for others to use for pathway discovery, and in doing so enrich our understanding of this fundamental source of biological sulfur. The work has widespread impact, from plant science through microbial ecology, all driven by structural and biochemical understanding of enzyme and protein function.

Committee	Research Committee D (Molecules, cells and industrial biotechnology)
Research Topics	Industrial Biotechnology, Microbiology, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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