ORCID Profile
0000-0003-3960-2212
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Publisher: American Chemical Society (ACS)
Date: 26-08-2019
DOI: 10.26434/CHEMRXIV.9725120.V1
Abstract: 2,3-Dihydroxypropanesulfonate (DHPS) is a major sulfur species in the biosphere. One important route for the production of DHPS includes sulfoglycolytic catabolism of sulfoquinovose (SQ) through the Embden-Meyerhof-Parnas (sulfo-EMP) pathway. SQ is a sulfonated carbohydrate present in plant and cyanobacterial sulfolipids (sulfoquinovosyl diacylglyceride and its metabolites) and is biosynthesised globally at a rate of around 10 billion tonnes per annum. The final step in the bacterial sulfo-EMP pathway involves reduction of sulfolactaldehyde (SLA) to DHPS, catalysed by an NADH-dependent SLA reductase. On the basis of conserved sequence motifs, we assign SLA reductase to the β-hydroxyacid dehydrogenase (β-HAD) family, making it the first ex le of a β-HAD enzyme that acts on a sulfonic acid, rather than a carboxylic acid substrate. We report crystal structures of the SLA reductase YihU from E. coli K-12 in its apo and cofactor-bound states, as well as the ternary complex YihU•NADH•DHPS with the cofactor and product bound in the active site. Conformational flexibility observed in these structures, combined with kinetic studies, confirm a sequential mechanism and provide evidence for dynamic domain movements that occur during catalysis. The ternary complex structure reveals a conserved sulfonate pocket in SLA reductase that recognises the sulfonate oxygens through hydrogen bonding to Asn174, Ser178, and the backbone amide of Arg123, along with an ordered water molecule. This triad of residues distinguishes these enzymes from classical β-HADs that act on carboxylate substrates. A comparison of YihU crystal structures with close structural homologues within the β-HAD family highlights key differences in the overall domain organization and identifies a unique peptide sequence that is predictive of SLA reductase activity.
Publisher: Proceedings of the National Academy of Sciences
Date: 24-01-2022
Abstract: Sulfoquinovose, a sulfosugar derivative of glucose, is produced by most photosynthetic organisms and contains up to half of all sulfur in the biosphere. Several pathways for its breakdown are known, though they provide access to only half of the carbon in sulfoquinovose and none of its sulfur. Here, we describe a fundamentally different pathway within the plant pathogen Agrobacterium tumefaciens that features oxidative desulfurization of sulfoquinovose to access all carbon and sulfur within the molecule. Biochemical and structural analyses of the pathway’s key proteins provided insights how the sulfosugar is recognized and degraded. Genes encoding this sulfoquinovose monooxygenase pathway are present in many plant pathogens and symbionts, alluding to a possible role for sulfoquinovose in plant host–bacteria interactions.
Publisher: American Chemical Society (ACS)
Date: 22-10-2019
DOI: 10.26434/CHEMRXIV.9725120.V2
Abstract: 2,3-Dihydroxypropanesulfonate (DHPS) is a major sulfur species in the biosphere. One important route for the production of DHPS includes sulfoglycolytic catabolism of sulfoquinovose (SQ) through the Embden-Meyerhof-Parnas (sulfo-EMP) pathway. SQ is a sulfonated carbohydrate present in plant and cyanobacterial sulfolipids (sulfoquinovosyl diacylglyceride and its metabolites) and is biosynthesised globally at a rate of around 10 billion tonnes per annum. The final step in the bacterial sulfo-EMP pathway involves reduction of sulfolactaldehyde (SLA) to DHPS, catalysed by an NADH-dependent SLA reductase. On the basis of conserved sequence motifs, we assign SLA reductase to the β-hydroxyacid dehydrogenase (β-HAD) family, making it the first ex le of a β-HAD enzyme that acts on a sulfonic acid, rather than a carboxylic acid substrate. We report crystal structures of the SLA reductase YihU from E. coli K-12 in its apo and cofactor-bound states, as well as the ternary complex YihU•NADH•DHPS with the cofactor and product bound in the active site. Conformational flexibility observed in these structures, combined with kinetic studies, confirm a sequential mechanism and provide evidence for dynamic domain movements that occur during catalysis. The ternary complex structure reveals a conserved sulfonate pocket in SLA reductase that recognises the sulfonate oxygens through hydrogen bonding to Asn174, Ser178, and the backbone amide of Arg123, along with an ordered water molecule. This triad of residues distinguishes these enzymes from classical β-HADs that act on carboxylate substrates. A comparison of YihU crystal structures with close structural homologues within the β-HAD family highlights key differences in the overall domain organization and identifies a unique peptide sequence that is predictive of SLA reductase activity.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3SC01594G
Publisher: Cold Spring Harbor Laboratory
Date: 14-03-2023
DOI: 10.1101/2023.03.13.532361
Abstract: Sulfolactate (SL) is a short-chain organosulfonate that is an important reservoir of sulfur in the biosphere. SL is produced by oxidation of sulfolactaldehyde (SLA), which in turn derives from sulfoglycolysis of the sulfosugar sulfoquinovose, or through oxidation of 2,3-dihydroxypropanesulfonate. Oxidation of SLA is catalyzed by SLA dehydrogenases belonging to the aldehyde dehydrogenase superfamily. We report that SLA dehydrogenase Rl GabD from the sulfoglycolytic bacterium Rhizobium leguminsarum SRDI565 can use both NAD + and NADP + as cofactor to oxidize SLA, and indicatively operates through a rapid equilibrium ordered mechanism. We report the cryo-EM structure of Rl GabD bound to NADH, revealing a tetrameric quaternary structure and supporting proposal of organosulfonate binding residues in the active site, and a catalytic mechanism. Sequence based homology searches identified SLA dehydrogenase homologs in a range of putative sulfoglycolytic gene clusters in bacteria predominantly from the phyla Actinobacteria, Firmicutes, and Proteobacteria. This work provides a structural and biochemical view of SLA dehydrogenases to complement our knowledge of SLA reductases, and provide detailed insights into a critical step in the organosulfur cycle. Sulfolactate is an important species in the biogeochemical sulfur cycle. Herein we report the 3D cryo-EM structure and kinetics of its biosynthetic enzyme, sulfolactaldehyde dehydrogenase.
Publisher: American Chemical Society (ACS)
Date: 23-02-2021
Publisher: American Chemical Society (ACS)
Date: 22-10-2019
DOI: 10.26434/CHEMRXIV.9725120
Abstract: 2,3-Dihydroxypropanesulfonate (DHPS) is a major sulfur species in the biosphere. One important route for the production of DHPS includes sulfoglycolytic catabolism of sulfoquinovose (SQ) through the Embden-Meyerhof-Parnas (sulfo-EMP) pathway. SQ is a sulfonated carbohydrate present in plant and cyanobacterial sulfolipids (sulfoquinovosyl diacylglyceride and its metabolites) and is biosynthesised globally at a rate of around 10 billion tonnes per annum. The final step in the bacterial sulfo-EMP pathway involves reduction of sulfolactaldehyde (SLA) to DHPS, catalysed by an NADH-dependent SLA reductase. On the basis of conserved sequence motifs, we assign SLA reductase to the β-hydroxyacid dehydrogenase (β-HAD) family, making it the first ex le of a β-HAD enzyme that acts on a sulfonic acid, rather than a carboxylic acid substrate. We report crystal structures of the SLA reductase YihU from E. coli K-12 in its apo and cofactor-bound states, as well as the ternary complex YihU•NADH•DHPS with the cofactor and product bound in the active site. Conformational flexibility observed in these structures, combined with kinetic studies, confirm a sequential mechanism and provide evidence for dynamic domain movements that occur during catalysis. The ternary complex structure reveals a conserved sulfonate pocket in SLA reductase that recognises the sulfonate oxygens through hydrogen bonding to Asn174, Ser178, and the backbone amide of Arg123, along with an ordered water molecule. This triad of residues distinguishes these enzymes from classical β-HADs that act on carboxylate substrates. A comparison of YihU crystal structures with close structural homologues within the β-HAD family highlights key differences in the overall domain organization and identifies a unique peptide sequence that is predictive of SLA reductase activity. br
Publisher: Cambridge University Press (CUP)
Date: 09-2021
DOI: 10.33774/CHEMRXIV-2021-08J01-V4
Abstract: Catabolism of sulfoquinovose (SQ, 6-deoxy-6-sulfoglucose), the ubiquitous sulfosugar produced by photosynthetic organisms, is an important component of the biogeochemical carbon and sulfur cycles. Here, we describe a new pathway for SQ degradation that involves oxidative desulfurization to release sulfite and enable utilization of the entire carbon skeleton of the sugar to support the growth of the plant pathogen Agrobacterium tumefaciens. SQ or its glycoside sulfoquinovosyl glycerol (SQGro) are imported into the cell by an ABC transporter system with an associated SQ binding protein. A sulfoquinovosidase hydrolyses the SQ glycoside and the liberated SQ is acted on by a flavin mononucleotide-dependent sulfoquinovose monooxygenase, in concert with an NADH-dependent flavin reductase, to release sulfite and 6-oxo-glucose. An NADPH-dependent oxidoreductase reduces the 6-oxo-glucose to glucose, enabling entry into primary metabolic pathways. Structural and biochemical studies provide detailed insights into the recognition of key metabolites by proteins in this pathway. Bioinformatic analyses reveal that the sulfoquinovose monooxygenase (smo) pathway is distributed across Alpha- and Betaproteobacteria and is especially prevalent within the Rhizobiales order. This strategy for SQ catabolism is distinct from previously described pathways as it enables the complete utilization of all carbons within SQ by a single organism with concomitant production of inorganic sulfite.
Publisher: American Chemical Society (ACS)
Date: 09-02-2021
DOI: 10.26434/CHEMRXIV.12974237
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 metabolises 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 shows 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 3D 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 transcriptional regulator 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 AMP, ADP, ATP, F6P, FBP, PEP, 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.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1CS00846C
Abstract: A biochemical, structural and mechanistic perspective on the pathways of sulfoglycolysis for catabolism of the sulfosugar sulfoquinovose.
Publisher: American Chemical Society (ACS)
Date: 30-01-2020
Publisher: American Chemical Society (ACS)
Date: 09-02-2021
DOI: 10.26434/CHEMRXIV.12974237.V3
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 metabolises 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 shows 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 3D 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 transcriptional regulator 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 AMP, ADP, ATP, F6P, FBP, PEP, 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.
Publisher: American Chemical Society (ACS)
Date: 23-09-2020
DOI: 10.26434/CHEMRXIV.12974237.V2
Abstract: The sulfosugar sulfoquinovose (SQ) is produced by essentially all photosynthetic organisms on earth and is metabolized bacteria through the process of sulfoglycolysis. The sulfoglycolytic Embden-Meyerhof-Parnas pathway metabolises 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 aldolase. Our data shows 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 3D structures of each of these enzymes, which reveal the presence of conserved sulfonate-binding pockets. We show that SQ isomerase acts preferentially on the b-anomer of SQ and reversibly produces both SF and sulforhamnose (SR), a previously unknown sugar that acts as a transcriptional regulator for the transcriptional repressor CsqR that regulates SQ-utilisation. We also demonstrate that SF kinase is a key regulatory enzyme for the pathway that experiences complex allosteric modulation by the metabolites AMP, ADP, ATP, F6P, FBP, PEP, and citrate. 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.
Publisher: American Society for Microbiology
Date: 20-07-2020
DOI: 10.1128/AEM.00750-20
Abstract: Sulfonate sulfur is a major form of organic sulfur in soils but requires biomineralization before it can be utilized by plants. Very little is known about the biochemical processes used to mobilize sulfonate sulfur. We show that a rhizobial isolate from soil, Rhizobium leguminosarum SRDI565, possesses the ability to degrade the abundant phototroph-derived carbohydrate sulfonate SQ through a sulfoglycolytic Entner-Doudoroff pathway. Proteomics and metabolomics demonstrated the utilization of this pathway during growth on SQ and provided evidence for gluconeogenesis. Unexpectedly, off-cycle sulfoglycolytic species were also detected, pointing to the complexity of metabolic processes within cells under conditions of sulfoglycolysis. Thus, rhizobial metabolism of the abundant sulfosugar SQ may contribute to persistence of the bacteria in the soil and to mobilization of sulfur in the pedosphere.
Publisher: American Chemical Society (ACS)
Date: 21-09-2020
DOI: 10.26434/CHEMRXIV.12974237.V1
Abstract: The sulfosugar sulfoquinovose (SQ) is produced by essentially all photosynthetic organisms on earth and is metabolized bacteria through the process of sulfoglycolysis. The sulfoglycolytic Embden-Meyerhof-Parnas pathway metabolises 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 aldolase. Our data shows 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 3D structures of each of these enzymes, which reveal the presence of conserved sulfonate-binding pockets. We show that SQ isomerase acts preferentially on the b-anomer of SQ and reversibly produces both SF and sulforhamnose (SR), a previously unknown sugar that acts as a transcriptional regulator for the transcriptional repressor CsqR that regulates SQ-utilisation. We also demonstrate that SF kinase is a key regulatory enzyme for the pathway that experiences complex allosteric modulation by the metabolites AMP, ADP, ATP, F6P, FBP, PEP, and citrate. 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.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mahima Sharma.