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on engineered biosynthesis of new polyene macrolides
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Polyene macrolide biosynthesis in streptomycetes and ..
NMR chemical shift tables and NMR spectra for compounds 1–5, list of genes for biosynthetic gene cluster, alignment of KR sequences for cluster, Cartesian coordinates for molecular modeling, graphical representations of minimum energy conformers for calculated lobosamide C stereoisomers ()
Effects of mepartricin, a polyene macrolide antibiotic, …
Strain JAU4234, identified as Streptomyces padanus, was isolated from soil collected in Jiangxi Province, China. It produced actinomycin X2, fungichromin, and a new polyene macrolide compound with antifungal activity, antifungalmycin 702. Antifungalmycin 702 had good general antifungal activity and may have potential future agricultural and/or clinical applications.
on engineered biosynthesis of new polyene ..
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Improved Antifungal Polyene Macrolides via Engineering …
Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A–C from a marine actinobacterium, sp., representing three new members of a small but growing family of bacterially produced polyene macrolactams. The lobosamides display growth inhibitory activity against the protozoan parasite (lobosamide A IC50 = 0.8 μM), the causative agent of human African trypanosomiasis (HAT). The biosynthetic gene cluster of the lobosamides was sequenced and suggests a conserved cluster organization among the 26-membered macrolactams. While determination of the relative and absolute configurations of many members of this family is lacking, the absolute configurations of the lobosamides were deduced using a combination of chemical modification, detailed spectroscopic analysis, and bioinformatics. We implemented a “molecules-to-genes-to-molecules” approach to determine the prevalence of similar clusters in other bacteria, which led to the discovery of two additional macrolactams, mirilactams A and B from . These additional analogs have allowed us to identify specific structure–activity relationships that contribute to the antitrypanosomal activity of this class. This approach illustrates the power of combining chemical analysis and genomics in the discovery and characterization of natural products as new lead compounds for neglected disease targets.