Identification and Characterization of Two Aryl Sulfotransferases from Deep-Sea Marine Fungi and Their Implications in the Sulfation of Secondary Metabolites DOI Creative Commons

Nicolas Graziano,

Beatriz Arce-López, Tristan Barbeyron

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(12), P. 572 - 572

Published: Dec. 20, 2024

Sulfation plays a critical role in the biosynthesis of small molecules, regulatory mechanisms such as hormone signaling, and detoxification processes (phase II enzymes). The sulfation reaction is catalyzed by broad family enzymes known sulfotransferases (SULTs), which have been extensively studied animals due to their medical importance, but also plant key processes. Despite identification some sulfated metabolites fungi, underlying fungal remain largely unknown. To address this knowledge gap, we conducted comprehensive search available genomes, resulting 174 putative SULT genes Ascomycota phylum. Phylogenetic analysis structural modeling revealed that these SULTs belong aryl sulfotransferase family, they are divided into two potential distinct clusters PAPS-dependent within kingdom. from marine fungi isolated deep-sea hydrothermal vents, Hortaea werneckii UBOCC-A-208029 (HwSULT) Aspergillus sydowii UBOCC-A-108050 (AsSULT), were selected representatives each cluster. Recombinant proteins expressed Escherichia coli biochemically characterized. HwSULT demonstrated high versatile activity, while AsSULT appeared more substrate-specific. Here, was used sulfate mycotoxin zearalenone, enhancing its cytotoxicity toward healthy feline intestinal cells.

Language: Английский

Polysaccharide sulfotransferases: the identification of putative sequences and respective functional characterisation DOI Creative Commons
Ravina Mistry, Dominic P. Byrne, David Starns

et al.

Essays in Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: May 7, 2024

Abstract The vast structural diversity of sulfated polysaccharides demands an equally diverse array enzymes known as polysaccharide sulfotransferases (PSTs). PSTs are present across all kingdoms life, including algae, fungi and archaea, their sulfation pathways relatively unexplored. Sulfated possess anti-inflammatory, anticoagulant anti-cancer properties have great therapeutic potential. Current identification using Pfam has been predominantly focused on the glycosaminoglycan (GAG) because pivotal roles in cell communication, extracellular matrix formation coagulation. As a result, our knowledge non-GAG structure function remains limited. major sulfotransferase families, Sulfotransfer_1 Sulfotransfer_2, display broad homology should enable capture wide assortment but limited PST sequence annotation. In addition, annotation is further restricted by paucity biochemical analyses PSTs. There now high-throughput robust assays for such colorimetric PAPS (3′-phosphoadenosine 5′-phosphosulfate) coupled assays, Europium-based fluorescent probes ratiometric PAP (3′-phosphoadenosine-5′-phosphate) detection, NMR methods activity product analysis. These techniques provide real-time direct measurements to enhance functional subsequent analysis tree life improve putative characterisation function. Improved sequences will utility biomedical biotechnological sectors.

Language: Английский

Citations

6
A Bacterial Sulfotransferase Catalyzes an Unusual Di‐Sulfation in Natural Products Biosynthesis DOI Creative Commons
Conor Pulliam, Lukuan Hou, Dan Xue

et al.

ChemBioChem, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Sulfation is a widely used strategy in nature to modify the solubility, polarity, and biological activities of molecules. The enzymes catalyzing sulfation, sulfotransferases (STs), are typically highly specific single sulfation site molecule. Herein, identification characterization sulfated adipostatins reported reveals novel sulfotransferase, AdpST, which responsible for di-sulfation at two sites adipostatins. initial bioinformatic analysis search adipostatin analogs from Streptomyces davaonensis DSM101723 identifies adpST 3'-phosphoadenosine-5'-phosphosulfate (PAPS) biosynthetic cassette, co-clustered with adipostatin-encoding type III polyketide synthase. Mono- di-sulfated discovered extracts S. DSM101723, whereas bacterial natural products has not been reported. Using series vivo vitro experiments, it confirmed that AdpST solely both mono- adipostatins, catalytic activity identified PAPS-dependent STs date. It further demonstrated dedicated PAPS cassette improves capacity. Lastly, determined shares similarity small group uncharacterized STs, suggesting presence additional unique nature, phylogenetically distant many characterized STs.

Language: Английский

Citations

0
Genome-wide identification and transcriptome-based expression profiling of Sulfotransferase superfamily genes in Mus musculus DOI Creative Commons
Junaid Habib Khan,

Samra Farooq,

S Shafqat

et al.

Published: April 1, 2025

Language: Английский

Citations

0
A new type of sulfation reaction: C-sulfonation for α,β-unsaturated carbonyl groups by a novel sulfotransferase SULT7A1 DOI Creative Commons
Katsuhisa Kurogi, Yoichi Sakakibara, Takuyu Hashiguchi

et al.

PNAS Nexus, Journal Year: 2024, Volume and Issue: 3(3)

Published: Feb. 29, 2024

Abstract Cytosolic sulfotransferases (SULTs) are cytosolic enzymes that catalyze the transfer of sulfonate group to key endogenous compounds, altering physiological functions their substrates. SULT O-sulfonation hydroxy groups or N-sulfonation amino substrate compounds. In this study, we report discovery C-sulfonation α,β-unsaturated carbonyl mediated by a new enzyme, SULT7A1, and human SULT1C4. Enzymatic assays revealed SULT7A1 is capable transferring from 3′-phosphoadenosine 5′-phosphosulfate α-carbon carbonyl-containing including cyclopentenone prostaglandins as representative Structural analyses suggest reaction catalyzed novel mechanism His Cys residues in active site. Ligand-activity demonstrated sulfonated 15-deoxy prostaglandin J2 exhibits antagonist activity against receptor EP2 prostacyclin IP. Modification via prostaglandin-sulfonating may regulate function gut. Discovery will broaden spectrum potential substrates SULTs.

Language: Английский

Citations

3
Functional divergence of conserved developmental plasticity genes between two distantly related nematodes DOI Creative Commons
Sara Wighard, Hanh Witte, Ralf J. Sommer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Abstract Genes diverge in form and function multiple ways over time; they can be conserved, acquire new roles, or eventually lost. However, the way genes at functional level is little understood, particularly plastic systems. We investigated this process using two distantly related nematode species, Allodiplogaster sudhausi Pristionchus pacificus . Both these nematodes display environmentally-influenced developmental plasticity of mouth-form feeding structures. This phenotype manipulated by growth on particular diets, making them ideal traits to investigate divergence between organisms. Using CRISPR-engineered mutations A. genes, we demonstrate examples various ancestral regulate how roles progressively diverge. examined four revealing distinct differences their conservation regulating mouth both species. Specifically, certain retain same characteristics, while others have acquired a function. Additionally, functions as switch which completely prevent phenotype, other quantitative effects, with knockouts displaying intermediate phenotypes. Remarkably, despite evolutionary distance, all were involved regulation. Finally, gene knock-out mutants engineered, key sulfatase-encoding acting downstream others, suggesting play major role plasticity. Together, study represents first mutant-based analysis evolution highly diverged offering insights into genetic mechanisms underlying phenotypic evolution. Article Summary While well-studied sequence level, resulting consequences are less known, Here, set found that studied control species; however, strong gene-specific effects even novel functions. Thus, there spectrum from full conservation, partial gain function; sulfation showing strongest during

Language: Английский

Citations

0
Identification and Characterization of Two Aryl Sulfotransferases from Deep-Sea Marine Fungi and Their Implications in the Sulfation of Secondary Metabolites DOI Creative Commons

Nicolas Graziano,

Beatriz Arce-López, Tristan Barbeyron

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(12), P. 572 - 572

Published: Dec. 20, 2024

Sulfation plays a critical role in the biosynthesis of small molecules, regulatory mechanisms such as hormone signaling, and detoxification processes (phase II enzymes). The sulfation reaction is catalyzed by broad family enzymes known sulfotransferases (SULTs), which have been extensively studied animals due to their medical importance, but also plant key processes. Despite identification some sulfated metabolites fungi, underlying fungal remain largely unknown. To address this knowledge gap, we conducted comprehensive search available genomes, resulting 174 putative SULT genes Ascomycota phylum. Phylogenetic analysis structural modeling revealed that these SULTs belong aryl sulfotransferase family, they are divided into two potential distinct clusters PAPS-dependent within kingdom. from marine fungi isolated deep-sea hydrothermal vents, Hortaea werneckii UBOCC-A-208029 (HwSULT) Aspergillus sydowii UBOCC-A-108050 (AsSULT), were selected representatives each cluster. Recombinant proteins expressed Escherichia coli biochemically characterized. HwSULT demonstrated high versatile activity, while AsSULT appeared more substrate-specific. Here, was used sulfate mycotoxin zearalenone, enhancing its cytotoxicity toward healthy feline intestinal cells.

Language: Английский

Citations

0