更新于：2024-11-01

MetDC

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 MetDC 相关的药物

SYNB-1353

靶点

MetDC x MetP

作用机制

MetDC刺激剂 [+3]

在研机构

Synlogic, Inc.

原研机构

Synlogic, Inc.

在研适应症

同型半胱氨酸尿症

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 MetDC 相关的临床试验

NCT05462132 / Completed临床1期

A Phase 1, Dose-escalation, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB1353 in Healthy Volunteers

This is a Phase 1, double-blind (Sponsor-open), placebo-controlled, randomized, dose-escalation, inpatient study using a multiple-ascending dose (MAD) design to assess the safety, tolerability, and PD of SYNB1353 in HVs.

开始日期2022-07-07

申办/合作机构

Synlogic, Inc.

100 项与 MetDC 相关的临床结果

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100 项与 MetDC 相关的转化医学

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0 项与 MetDC 相关的专利（医药）

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458

项与 MetDC 相关的文献（医药）

2024-12-01·International Journal of Biological Macromolecules

Discovery and characterization of temperature adaptation modules by mining L-glutamate decarboxylase derived from psychrophilic microorganisms

Article

作者: Wang, Qiong ; Song, Chenshuo ; Qiao, Jun ; Luo, Jie ; Cheng, Zhongyi ; Liu, Zhongmei ; Zhou, Zhemin ; Han, Laichuang

Directed alterations of the enzyme's temperature adaptations, such as thermostability and optimal catalytic temperature (T_opt), are usually the way to go in order to meet the applications, however they are limited by the understanding between protein structure and function. Glutamate decarboxylase (GADs) is a common enzyme in the food industry. In this study, we identified and characterized three novel L-glutamate decarboxylases from psychrophilic microorganisms. Interestingly, the two enzymes (Gad Psy.Y/Gad Psy.F) showed significant differences in temperature adaptation. Through multiple sequence alignment and structural analysis, two potential regions that may affect the T_opt and thermostability of the GAD, termed temperature adaptation modules (TAMs), were targeted. To validate the role of TAMs, we constructed mutants with bi-directional transplants of TAMs, which ultimately significantly altered the temperature adaptation of Gad Psy.Y and Gad Psy.F. Molecular dynamics simulations analysis demonstrated that the introduction and disruption of salt bridges in the mutant TAMs are crucial for this alteration. These findings deepen the understanding of the mechanisms of protein temperature adaptation and provide implications for protein engineering, while also offering advantageous enzymes to support the biosynthesis of GABA.

2024-12-01·Bioresource Technology

Highly efficient bio-production of putrescine from L-arginine with arginase and L-ornithine decarboxylase in engineered Escherichia coli

Article

作者: Du, Min ; Zhang, Alei ; Chen, Kequan ; Wang, Jing ; He, Junchen ; Wang, Xin

To achieve industrial-scale putrescine production, a high efficient bio-synthesis of putrescine involving arginase (ARG, EC 3.5.3.1) and L-ornithine decarboxylase was evaluated here. Among the four arginases tested, ARG_BT from Bos Taurus showed the highest activity (1966 U/mg). Compared to the L-arginine decarboxylase (ADC) pathway, the strain expressing ARG_BT and L-ornithine decarboxylase (SpeC) produced 28.7 g/L putrescine, a 38.6 % increase. Two pyridoxal phosphate (PLP) salvage pathways were evaluated, and the strain BL-P_Tac-PdxK co-expressed pyridoxal kinase (PdxK) performed better. D-Glucose was used as the co-substrate to improve the putrescine titer further. Under optimal conditions, 43.6 g/L putrescine was produced from 87.1 g/L L-arginine, and 76 g/L putrescine was synthesized on a 0.5 L scale. Using L-arginine fermentation broth (60 g/L) as the substrate, a titer of 30 g/L putrescine was achieved. This efficient biotransformation process presented here enables feasible industrial-scale putrescine production.

2024-11-01·Journal of Bioscience and Bioengineering

Structural and functional analysis of l-methionine oxidase identified through sequence data mining

Article

作者: Araseki, Hayato ; Kawamura, Yui ; Nakano, Shogo ; Chisuga, Taichi ; Sugiura, Sayaka

l-Amino acid oxidase (LAAO), an FAD-dependent enzyme, catalyzes the oxidation of l-amino acids (l-AAs) to their corresponding imino acids. While LAAOs, which can oxidize charged or aromatic l-AAs specifically, have been extensively characterized across various species, LAAOs that have high specificity toward alkyl-chain l-AAs, such as l-Met, are hardly characterized for now. In this study, we screened a highly specific l-Met oxidizing LAAOs from Burkholderiales bacterium (BbMetOx) and Undibacterium sp. KW1 (UndMetOx) using sequence similarity network (SSN) analysis. These enzymes displayed an order of magnitude higher specific activity towards l-Met compared to other l-AAs. Enzyme activity assays showed that these LAAOs operate optimally at moderate condition because the optimal pH and T_m values were pH 7.0 and 58-60°C. We determined the crystal structures of wild-type BbMetOx (BbMetOx(WT)) and an inactivated mutant, BbMetOx (K304A), at 2.7 Å and 2.2 Å resolution, respectively. The overall structure of BbMetOx is closely similar to other known LAAOs of which structures were determined. Comparative analysis of the BbMetOx structures revealed significant conformational changes in the catalytic domain, particularly a movement of approximately 8 Å in the C_α atom of residue Y180. Further analysis highlighted four residues, i.e., Y180, M182, F300, and M302, as critical for l-Met recognition, with alanine substitution at these positions resulting in loss of activity. This study not only underscores the utility of SSN for discovering novel LAAOs but also advances our understanding of substrate specificity in this enzyme family.