The aminoshikimate pathway of formation of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of ansamycin and other antibiotics is reviewed. In this biosynthesis, genes for kanosamine formation have been recruited from other genomes, to provide a nitrogenous precursor. Kanosamine is then phosphorylated and converted by common cellular enzymes into 1-deoxy-1-imino-erythrose 4-phosphate, the substrate for the formation of aminoDAHP. This is converted via 5-deoxy-5-aminodehydroquinic acid and 5-deoxy-5-aminodehydroshikimic acid into AHBA. Remarkably, the pyridoxal phosphate enzyme AHBA synthase seems to have two catalytic functions: As a homodimer, it catalyzes the last reaction in the pathway, the aromatization of 5-deoxy-5-aminodehydroshikimic acid, and at the beginning of the pathway in a complex with the oxidoreductase RifL it catalyzes the transamination of UDP-3-keto-D-glucose. The AHBA synthase gene also serves as a useful tool in the genetic screening for new ansamycins and other AHBA-derived natural products.
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http://dx.doi.org/10.1038/ja.2010.139 | DOI Listing |
Biomolecules
August 2024
Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain.
Biol Pharm Bull
February 2024
Department of Pharmacology, Showa University Graduate School of Pharmacy.
Non-alcoholic steatohepatitis (NASH), which is on the rise due to the increasing obese population and changing lifestyles, causes fibrosis over time and carries the risk of progression to cirrhosis and hepatocellular carcinoma. However, there are no approved effective treatments for NASH. Recent studies suggest that increased lipid metabolism and reduced nitric oxide content are responsible for NASH; 3-amino-4-hydroxy benzoic acid (AHBA) was identified as an inhibitor for the phosphatase activity of soluble epoxy hydrolase, which in turn inhibits lipid metabolism and endothelial nitric oxide synthase activity.
View Article and Find Full Text PDFMicrob Cell Fact
August 2023
Biological Science Research, Kao Corporation, 1334 Minato, Wakayama, Wakayama, 640-8580, Japan.
Background: Microbial production of aromatic chemicals is an attractive method for obtaining high-performance materials from biomass resources. A non-proteinogenic amino acid, 4-amino-3-hydroxybenzoic acid (4,3-AHBA), is expected to be a precursor of highly functional polybenzoxazole polymers; however, methods for its microbial production have not been reported. In this study, we attempted to produce 4,3-AHBA from glucose by introducing 3-hydroxylation of 4-aminobenzoic acid (4-ABA) into the metabolic pathway of an industrially relevant bacterium, Corynebacterium glutamicum.
View Article and Find Full Text PDFiScience
August 2023
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Soluble epoxide hydrolase is a widely distributed bifunctional enzyme that contains N-terminal phosphatase (N-phos) and C-terminal epoxide hydrolase (C-EH) domains. C-EH hydrolyzes anti-inflammatory epoxy-fatty acids to corresponding diols and contributes to various inflammatory conditions. However, N-phos has been poorly examined.
View Article and Find Full Text PDFEur J Med Chem
December 2022
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China; Tongji University School of Medicine, 1239 Siping Road, Shanghai, China. Electronic address:
Triene-ansamycins such as ansatrienins and cytotrienins are characterized by three conjugated double bond motifs within a 21-membered benzenoid ansamycins. Their structural diversity exists in the different substituents in the C-11 or C-13 side chain or in the 3-amino-5-hydroxy benzoic acid moiety. More complex derivatives have been reported with fused ring systems which may be produced via intramolecular cycloaddition between phenol and triene.
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