Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:1571-72-8 (3,4-AHBA)
 10 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In grixazone biosynthesis by Streptomyces griseus, a key intermediate 3-amino-4-hydroxybenzoic acid (3,4-AHBA) is converted to another key intermediate 3-amino-4-hydroxybenzaldehyde (3,4-AHBAL). Two genes griC and griD in the grixazone biosynthesis gene cluster were found to be responsible for this conversion, because disruption of each gene resulted in the extracellular accumulation of 3-acetylamino-4-hydroxybenzoic acid, a shunt product from 3,4-AHBA. Significant sequence similarity of GriC to AMP-binding proteins and of GriD to NAD(P)-dependent aldehyde dehydrogenases suggested that GriC and GriD constituted an ATP- and NAD(P)-dependent carboxylic acid reductase (CAR) catalyzing reduction of 3,4-AHBA to produce 3,4-AHBAL through acyl-AMP formation, as is found for the reactions catalyzed by some CARs. griG encoding a benzoate transporter homologue in the grixazone biosynthesis gene cluster was nonessential for grixazone biosynthesis but probably enhanced the membrane permeability for 3,4-AHBA. Simultaneous overexpression of griC, griD, and griG in S. griseus mutant cells deficient in an acetyltransferase responsible for N-acetylation of 3,4-AHBA led to efficient bioconversion of exogenously added 3,4-AHBA to 3,4-AHBAL. This system also turned out to be useful for reduction of some aryl carboxylates to the corresponding aryl aldehydes.
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PMID:GriC and GriD constitute a carboxylic acid reductase involved in grixazone biosynthesis in Streptomyces griseus. 1761 96

Many natural products contain epoxyquinone pharmacophore with unknown biosynthetic mechanisms. Recent genetic analysis of the asukamycin biosynthetic gene cluster proposed enzyme candidates related to epoxyquinone formation for manumycin-type metabolites. Our biochemical studies reveal that 3-amino-4-hydroxyl benzoic acid (3,4-AHBA) precursor is activated and loaded on aryl carrier protein (AsuC12) by ATP-dependent adenylase (AsuA2). AsuE1 and AsuE3, both single-component flavin-dependent monooxygenases, catalyze the exquisite regio- and enantiospecific postpolyketide synthase (PKS) assembly oxygenations. AsuE1 installs a hydroxyl group on the 3,4-AHB ring to form a 4-hydroxyquinone moiety, which is epoxidized by AsuE3 to yield the epoxyquinone functionality. Despite being a single-component monooxygenase, AsuE1 activity is elicited by AsuE2, a pathway-specific flavin reductase. We further demonstrate that the epoxyquinone moiety is critical for anti-MRSA activity by analyzing the bioactivity of various manumycin-type metabolites produced through mutasynthesis.
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PMID:Tandem enzymatic oxygenations in biosynthesis of epoxyquinone pharmacophore of manumycin-type metabolites. 2389 3