ABSTRACT
ATEG_08451 in Aspergillus terreus, here named atrochrysone carboxylic acid synthase (ACAS), is a nonreducing, iterative type I polyketide synthase that contains no thioesterase domain. In vitro, reactions of ACAS with malonyl-CoA yielded a polyketide intermediate, probably attached to its acyl carrier protein (ACP). The addition of ATEG_08450, here named atrochrysone carboxyl ACP thioesterase (ACTE), to the reaction resulted in the release of products derived from atrochrysone carboxylic acid, such as atrochrysone and endocrocin. ACTE, belonging to the beta-lactamase superfamily, thus appears to be a novel type of thioesterase responsible for product release in polyketide biosynthesis. These findings show that ACAS synthesizes the scaffold of atrochrysone carboxylic acid from malonyl-CoA, and that ACTE hydrolyzes the thioester bond between the ACP of ACAS and the intermediate to release atrochrysone carboxylic acid as the reaction product.
Subject(s)
Anthracenes/metabolism , Polyketide Synthases/metabolism , Thiolester Hydrolases/metabolism , Acyl Carrier Protein/metabolism , Anthracenes/chemistry , Anthraquinones/metabolism , Aspergillus/enzymology , Catalysis , Malonyl Coenzyme A/metabolism , Protein Structure, Tertiary , beta-Lactamases/metabolismABSTRACT
Since glycosidase and glycosyltransferase inhibitors, composed of carba-sugars, have recently attracted much attention, it is desirable to develop effective preparative routes for provision of new carba-sugar derivatives of potential biological interest. 1,2:3,6-Dianhydro-5a-carba-alpha-glucopyranose was here chosen for study of synthetic utility, and demonstrated to be a promising intermediate for supplying several carba-beta-glycosylamines and N-linked dicarba-oligosaccharides. An N-linked 5a,5a'-dicarbalactose derivative obtained here was found to be a strong alpha-galactosidase inhibitor (IC50 1.2 microM, green coffee beans).
Subject(s)
Alkanes/chemistry , Amino Sugars/chemical synthesis , Disaccharides/chemical synthesis , Galactose/chemical synthesis , Glycoside Hydrolases/antagonists & inhibitors , Heterocyclic Compounds, 3-Ring/chemistry , Amino Sugars/chemistry , Disaccharides/chemistry , Galactose/chemistry , Glycoside Hydrolases/chemistryABSTRACT
In addition to (+)-, (-)- and (+/-)-heliannuol E, growth-inhibitory activities of five synthetic chromans and four tetrahydrobenzo[b]oxepins were examined against oat and cress. All heliannuol E isomers exhibited similar biological activities against cress, whereas when tested against oat roots, the unnatural optical isomer (+) showed no inhibitory activity. Four brominated chromans and two tetrahydrobenzo[b]oxepin derivatives also showed apparent inhibition against both cress and oat.
Subject(s)
Avena/growth & development , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Flowers/chemistry , Helianthus/chemistry , Lepidium sativum/growth & development , Plant Growth Regulators/pharmacology , Plant Roots/growth & development , Sesquiterpenes/pharmacology , Avena/drug effects , Bridged Bicyclo Compounds, Heterocyclic/isolation & purification , Cotyledon/drug effects , Cotyledon/growth & development , Hypocotyl/drug effects , Hypocotyl/growth & development , Lepidium sativum/drug effects , Molecular Conformation , Molecular Structure , Plant Growth Regulators/isolation & purification , Plant Roots/drug effects , Sesquiterpenes/isolation & purificationABSTRACT
Convenient synthesis and chemical modification of the potent alpha-L-fucosidase inhibitor, 5a-carba-alpha-DL-fucopyranosylamine (1), are described. Among seven N-substituted and three cyclic isourea derivatives newly prepared, the N-octyl derivative was found to be the strongest inhibitor of alpha-L-fucosidase (bovine kidney) more potent (K(i)=0.016 microM) than deoxyfuconojirimycin (K(i)=0.031 microM) with p-nitrophenyl-alpha-L-fucopyranoside as the substrate.
