Molecular basis of sulfosugar selectivity in sulfoglycolysis

DOI: 10.1021/acscentsci.0c01285

Authors: Mahima Sharma (University of York) , Palika Abayakoon (Bio21 Molecular Science and Biotechnology Institute; University of Melbourne) , Ruwan Epa (Bio21 Molecular Science and Biotechnology Institute; University of Melbourne) , Yi Jin (University of York) , James P. Lingford (he Walter and Eliza Hall Institute of Medical Research; Bio21 Molecular Science and Biotechnology Institute; University of Melbourne) , Tomohiro Shimada (Meiji University) , Masahiro Nakano (Kyoto University) , Janice W.-y. Mui (Bio21 Molecular Science and Biotechnology Institute; University of Melbourne) , Akira Ishihama (Hosei University) , Ethan D. Goddard-borger (The Walter and Eliza Hall Institute of Medical Research; Bio21 Molecular Science and Biotechnology Institute; University of Melbourne) , Gideon J. Davies (University of York) , Spencer J. Williams (Bio21 Molecular Science and Biotechnology Institute; University of Melbourne)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Central Science , VOL 20

State: Published (Approved)
Published: February 2021
Diamond Proposal Number(s): 13587 , 18598 , 24948

Abstract: The sulfosugar sulfoquinovose (SQ) is produced by essentially all photosynthetic organisms on Earth and is metabolized by bacteria through the process of sulfoglycolysis. The sulfoglycolytic Embden–Meyerhof–Parnas pathway metabolizes SQ to produce dihydroxyacetone phosphate and sulfolactaldehyde and is analogous to the classical Embden–Meyerhof–Parnas glycolysis pathway for the metabolism of glucose-6-phosphate, though the former only provides one C3 fragment to central metabolism, with excretion of the other C3 fragment as dihydroxypropanesulfonate. Here, we report a comprehensive structural and biochemical analysis of the three core steps of sulfoglycolysis catalyzed by SQ isomerase, sulfofructose (SF) kinase, and sulfofructose-1-phosphate (SFP) aldolase. Our data show that despite the superficial similarity of this pathway to glycolysis, the sulfoglycolytic enzymes are specific for SQ metabolites and are not catalytically active on related metabolites from glycolytic pathways. This observation is rationalized by three-dimensional structures of each enzyme, which reveal the presence of conserved sulfonate binding pockets. We show that SQ isomerase acts preferentially on the β-anomer of SQ and reversibly produces both SF and sulforhamnose (SR), a previously unknown sugar that acts as a derepressor for the transcriptional repressor CsqR that regulates SQ-utilization. We also demonstrate that SF kinase is a key regulatory enzyme for the pathway that experiences complex modulation by the metabolites SQ, SLA, AMP, ADP, ATP, F6P, FBP, PEP, DHAP, and citrate, and we show that SFP aldolase reversibly synthesizes SFP. This body of work provides fresh insights into the mechanism, specificity, and regulation of sulfoglycolysis and has important implications for understanding how this biochemistry interfaces with central metabolism in prokaryotes to process this major repository of biogeochemical sulfur.

Journal Keywords: Peptides and proteins; Carbohydrates; Genetics; Metabolism; Glycolysis

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

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