Last update 01 Nov 2024

oxlT

Last update 01 Nov 2024

Basic Info

Synonyms-

Introduction

Anion transporter that carries out the exchange of divalent oxalate with monovalent formate, the product of oxalate decarboxylation, at the plasma membrane, and in doing so catalyzes the vectorial portion of a proton-motive metabolic cycle that drives ATP synthesis.

Drugs associated with oxlT

SYNB-8802

Target

frc x oxdC x oxlT x scaaE3

Mechanism

frc stimulants [+5]

Active Org.

Synlogic, Inc.

Originator Org.

Synlogic, Inc.

Active Indication

Hyperoxaluria [+1]

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with oxlT

NCT05377112 / CompletedEarly Phase 1

A Double-Blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB8802v1 in Subjects With History of Gastric Bypass Surgery or Short-bowel Syndrome

Study SYNB8802-CP-002 is designed to assess safety, tolerability, and oxalate lowering, in subjects with a history of gastric bypass surgery or short-bowel syndrome. In addition, this study will explore other PD effects relative to baseline as well as predictors of efficacy and tolerability.

Start Date29 Mar 2022

Sponsor / Collaborator

Synlogic, Inc.

NCT04629170 / CompletedPhase 1

A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB8802 in Healthy Volunteers and in Patients With Enteric Hyperoxaluria

This Phase 1a/b, first-in-human, multiple dose-escalation, randomized, double-blinded, placebo-controlled study is evaluating SYNB8802 in healthy volunteers (HV) and subjects diagnosed with enteric hyperoxaluria (EH). Eligible subjects receive investigational product (IP) and undergo safety monitoring, evaluations, and subsequent follow-up after IP administration.
In Part 2, all evaluations and assessments throughout this study may be conducted either at the clinical site or by a home healthcare professional at an alternative location (e.g., EH patient's home, hotel).

Start Date04 Nov 2020

Sponsor / Collaborator

Synlogic, Inc.

100 Clinical Results associated with oxlT

100 Translational Medicine associated with oxlT

0 Patents (Medical) associated with oxlT

Literatures (Medical) associated with oxlT

01 Aug 2024·Current Microbiology

Core Transcriptome of Hydrogen Producing Marine Vibrios Reveals Contribution of Glycolysis in Their Efficient Hydrogen Production

Article

Author: Sawabe, Tomoo ; Sato, Yoshihiro ; Mino, Sayaka ; Thompson, Fabiano

Pyruvate (Pyr) is the end product of the glycolysis pathway. Pyr is also renewable and is further metabolized to produce formate, which is the precursor of H₂, via pyruvate formate lyase (PFL) under anaerobic conditions. The formate is excluded and re-imported via the formate channel and is then converted to H₂ via the formate hydrogenlyase (FHL) complex. In H₂ producing marine vibrios, such as Vibrio tritonius and Vibrio porteresiae in the Porteresiae clade of the family Vibrionaceae, apparent but inefficient H₂ production from Pyr has been observed. To elucidate the molecular mechanism of why this inefficient H₂ production is observed in Pry-metabolized marine vibrio cells and how glycolysis affects those H₂ productions of marine vibrios, the "Core Transcriptome" approach to find common gene expressions of those two major H₂ producing Vibrio species in Pyr metabolism was first applied. In the Pyr-metabolized vibrio cells, genes for the "Phosphoenolpyruvate (PEP)-Pyruvate-Oxalate (PPO)" node, due to energy saving, and PhoB-, RhaR-, and DeoR-regulons were regulated. Interestingly, a gene responsible for oxalate/formate family antiporter was up-regulated in Pyr-metabolized cells compared to those of Glc-metabolized cells, which provides new insights into the uses of alternative formate exclusion mechanics due to energy deficiencies in Pyr-metabolized marine vibrios cells. We further discuss the contribution of the Embden-Meyerhof-Parnas (EMP) pathway to efficient H₂ production in marine vibrios.

25 Jan 2024·The Journal of Physical Chemistry Letters

Accelerated Molecular Dynamics and AlphaFold Uncover a Missing Conformational State of Transporter Protein OxlT

Article

Author: Jaunet-Lahary, Titouan ; Okazaki, Kei-Ichi ; Yamashita, Atsuko ; Ohnuki, Jun

Transporter proteins change their conformations to carry their substrate across the cell membrane. The conformational dynamics is vital to understanding the transport function. We have studied the oxalate transporter (OxlT), an oxalate:formate antiporter from Oxalobacter formigenes, significant in avoiding kidney stone formation. The atomic structure of OxlT has been recently solved in the outward-open and occluded states. However, the inward-open conformation is still missing, hindering a complete understanding of the transporter. Here, we performed a Gaussian accelerated molecular dynamics simulation to sample the extensive conformational space of OxlT and successfully predicted the inward-open conformation where cytoplasmic substrate formate binding was preferred over oxalate binding. We also identified critical interactions for the inward-open conformation. The results were complemented by an AlphaFold2 structure prediction. Although AlphaFold2 solely predicted OxlT in the outward-open conformation, mutation of the identified critical residues made it partly predict the inward-open conformation, identifying possible state-shifting mutations.

01 Jan 2023·Frontiers in microbiology

Expanding the taxonomic and environmental extent of an underexplored carbon metabolism-oxalotrophy.

Article

Author: Sonke, Alexander ; Trembath-Reichert, Elizabeth

Oxalate serves various functions in the biological processes of plants, fungi, bacteria, and animals. It occurs naturally in the minerals weddellite and whewellite (calcium oxalates) or as oxalic acid. The environmental accumulation of oxalate is disproportionately low compared to the prevalence of highly productive oxalogens, namely plants. It is hypothesized that oxalotrophic microbes limit oxalate accumulation by degrading oxalate minerals to carbonates via an under-explored biogeochemical cycle known as the oxalate-carbonate pathway (OCP). Neither the diversity nor the ecology of oxalotrophic bacteria is fully understood. This research investigated the phylogenetic relationships of the bacterial genes oxc, frc, oxdC, and oxlT, which encode key enzymes for oxalotrophy, using bioinformatic approaches and publicly available omics datasets. Phylogenetic trees of oxc and oxdC genes demonstrated grouping by both source environment and taxonomy. All four trees included genes from metagenome-assembled genomes (MAGs) that contained novel lineages and environments for oxalotrophs. In particular, sequences of each gene were recovered from marine environments. These results were supported with marine transcriptome sequences and description of key amino acid residue conservation. Additionally, we investigated the theoretical energy yield from oxalotrophy across marine-relevant pressure and temperature conditions and found similar standard state Gibbs free energy to "low energy" marine sediment metabolisms, such as anaerobic oxidation of methane coupled to sulfate reduction. These findings suggest further need to understand the role of bacterial oxalotrophy in the OCP, particularly in marine environments, and its contribution to global carbon cycling.

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oxlT

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