RESUMO
The natural products isatropoloneâ A-C (1-3) were reisolated from Streptomyces Gö66, with 1 and 3 showing potent activity against Leishmania donovani. They contain a rare tropolone ring derived from a typeâ II polyketide biosynthesis pathway. Their biosynthesis was elucidated by labeling experiments, analysis of the biosynthesis gene cluster, its partial heterologous expression, and structural characterization of various intermediates. Owing to their 1,5-diketone moiety, they can react with ammonia, amines, lysine, and lysine-containing peptides and proteins, which results in the formation of a covalent bond and subsequent pyridine ring formation. Their fluorescence properties change upon amine binding, enabling the simple visualization of reacted amines including proteins.
Assuntos
Produtos Biológicos/metabolismo , Vias Biossintéticas , Corantes Fluorescentes/metabolismo , Streptomyces/metabolismo , Tropolona/metabolismo , Aminas/metabolismo , Animais , Antiparasitários/química , Antiparasitários/metabolismo , Antiparasitários/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Família Multigênica , Ratos , Streptomyces/química , Streptomyces/enzimologia , Streptomyces/genética , Tropolona/química , Tropolona/farmacologiaRESUMO
Untwinned single crystals of the actinomycins D and Z3 that diffracted to atomic resolution could be obtained for the first time. Low-temperature data collection and a new ab initio method for solving the structures led to precise crystal structures which showed, for example, that the unit cell of actinomycin D contains three molecules, two of which are present in the form of a hydrogen-bridged dimer related by a pseudo-twofold axis (see picture).