A selective antibiotic for Lyme disease.

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining its selectivity. Hygromycin A cleared the B. burgdorferi infection in mice, including animals that ingested the compound in a bait, and was less disruptive to the fecal microbiome than clinically relevant antibiotics. This selective antibiotic holds the promise of providing a better therapeutic for Lyme disease and eradicating it in the environment.

Production of Bioactive 3'-Hydroxystilbene Compounds Using the Flavin-Dependent Monooxygenase Sam5.

The flavin-dependent monooxygenase Sam5 was previously reported to be a bifunctional hydroxylase with a coumarte 3-hydroxylase and a resveratrol 3'-hydroxylase activity. In this article, we showed the Sam5 enzyme has 3'-hydroxylation activities for methylated resveratrol (pinostilbene and pterostilbene), hydroxylated resveratrol (oxyresveratrol) and glycosylated resveratrol (piceid) as substrates. However, the use of piceid, a glycone type stilbene, as a substrate for bioconversion experiments with the Sam5 enzyme expressed in, Escherichia coli does not convert to the hydroxylated compound astringin, but it has converted in vitro enzyme reactions. Finally, we report a novel catalytic activity of Sam5 monooxygenase for the synthesis of piceatannol derivatives, 3'-hydroxylated stilbene compounds. Development of this bioproduction method for the hydroxylation of stilbenes is challenging because of the difficulty in expressing P450-type hydroxylase in E. coli and regionspecific chemical synthesis.

Characterization of the antioxidant fraction of Trapa japonica pericarp and its hepatic protective effects in vitro and in vivo.

The ethanolic extract of Trapa japonica pericarp (TJP) and its various fractions were evaluated for their antioxidant potential. The ethyl acetate fraction (EF) from TJP exhibited significant antioxidant and protective effects against tert-butylhydroperoxide (t-BHP)-induced oxidative damage in vitro and in vivo. In vitro experimental results showed that the EF suppressed t-BHP-induced damage in Chang cells by inhibiting reactive oxygen species generation and regulating the mitochondrial membrane potential. Furthermore, western blot analysis showed that the EF effectively inhibited t-BHP-induced apoptosis by suppressing caspase-3, caspase-7, caspase-8, and caspase-9. In the in vivo study, the EF significantly prevented serum increases in glutamate oxaloacetate transaminase and glutamate pyruvate transaminase and hepatic malondialdehyde levels caused by t-BHP. Furthermore, the EF markedly increased hepatic superoxide dismutase, catalase, and glutathione levels. Histopathological examinations further confirmed that the EF could protect the liver from t-BHP-induced oxidative injury. These findings indicate that the EF could be developed as a therapy or to prevent hepatic injury.

Structures and biological activities of azaphilones produced by Penicillium sp. KCB11A109 from a ginseng field.

Twelve metabolites, including five highly oxygenated azaphilones, geumsanols A-E, along with seven known analogues were isolated from Penicillium sp. KCB11A109, a fungus derived from a ginseng field. Their structures were assigned by spectroscopic means (NMR and MS), and stereochemistries were determined by extensive spectroscopic analyses ((1)H-(1)H coupling constants, NOESY, and HETLOC) and chemical derivatizations (modified Mosher's method and acetonide formation). The isolates were evaluated for their anticancer, antimicrobial, antimalarial activities, and phenotypic effects in zebrafish development. Of these compounds possessing no pyranoquinone core, only geumsanol E exhibited cytotoxic activities and toxic effects on zebrafish embryos, suggesting that a double bond at C-11 and C-12 is important for biological activity.