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Laboratory evolution of with a natural vitamin B analog reveals roles for cobamide uptake and adenosylation in methionine synthase-dependent growth.
J Bacteriol
January 2025
Department of Plant & Microbial Biology, University of California Berkeley, Berkeley, California, USA.
Bacteria encounter chemically similar nutrients in their environment, which impact their growth in distinct ways. Among such nutrients are cobamides, the structurally diverse family of cofactors related to vitamin B (cobalamin), which function as cofactors for diverse metabolic processes. Given that different environments contain varying abundances of different cobamides, bacteria are likely to encounter cobamides that enable them to grow robustly and also those that do not function efficiently for their metabolism.
View Article and Find Full Text PDFEfficient Spermidine Production Using a Multi-Enzyme Cascade System Utilizing Methionine Adenosyltransferase from Lactobacillus fermentum with Reduced Product Inhibition and Acidic pH Preference.
J Biotechnol
January 2025
The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Avenue, Wuxi, Jiangsu 214122, China; School of Health Sciences, Fuyao University of Science & Technology, Fuzhou, Fujian Province, China. Electronic address:
Methionine adenosyltransferases (MATs; EC 2.5.1.
View Article and Find Full Text PDFBacterial indole-3-propionic acid inhibits macrophage IL-1β production through targeting methionine metabolism.
Sci China Life Sci
January 2025
State Key Laboratory of Livestock and Poultry Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
The gut microbiota plays key roles in host health by shaping the host immune responses through their metabolites, like indole derivatives from tryptophan. However, the direct role of these indole derivatives in macrophage fate decision and the underlying mechanism remains unknown. Here, we found that bacterial indole-3-propionic acid (IPA) downregulates interleukin-1beta (IL-1β) production in M1 macrophages through inhibition of nuclear factor-kappa B (NF-κB) signaling.
View Article and Find Full Text PDFHomozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.
View Article and Find Full Text PDFDiscovery of 2(1)-Quinoxalinone Derivatives as Potent and Selective MAT2A Inhibitors for the Treatment of MTAP-Deficient Cancers.
J Med Chem
January 2025
Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China.
Article Synopsis
- MAT2A is a promising target for cancer treatment, especially in tumors with MTAP gene deletion, but there are challenges in ensuring the selectivity of MAT2A inhibitors for these specific cancers.
- Recent research led to the identification of new MAT2A inhibitors with a unique 2(1)-quinoxalinone structure that effectively inhibit MAT2A and selectively target MTAP-deficient cancer cells.
- One of the novel compounds demonstrated strong pharmacokinetic properties and showed enhanced anticancer effects in models with MTAP-deficient tumors, highlighting potential advancements in drug development for these cancer types.
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