Synthesis and biological evaluation of coprinoferrin, an acylated tripeptide hydroxamate siderophore.

Coprinoferrin (CPF), originally isolated from a genetically engineered strain (ΔlaeA) of the mushroom fungus Coprinopsis cinerea, is an acylated tripeptide hydroxamate consisting of tandem aligned N5-hexanoyl-N5-hydroxy-L-ornithine with modifications of N-acetyl and C-carboxamide. These unique chemical properties make CPF an iron(III) binder (siderophore), which helps in iron acquisition from the environment and promotes hyphal growth as well as fruiting body formation in C. cinerea. However, CPF's detailed mode of action remains enigmatic. In this study, we have accomplished the synthesis of CPF from N-Boc-L-glutamic acid 5-benzyl ester. The physicochemical characteristics, spectroscopic features, and biological activity observed in the synthetic CPF closely match those of natural CPF. This alignment provides unequivocal confirmation of the proposed chemical structure, facilitating a deeper understanding of its physiological role in nature, particularly in fruiting body formation.

A proposed antioxidation mechanism of ergothioneine based on the chemically derived oxidation product hercynine and further decomposition products.

Ergothioneine (ERGO), a thiohistidine betaine, exists in various fungi, plants, and animals. Humans take in ERGO from their diet. ERGO is a strong biological antioxidant, but there are only a limited number of reports about its redox mechanism. The purpose of this study was to clarify the oxidation mechanism of ERGO. Reactions of ERGO with chemical oxidants were performed. The oxidation products of ERGO were analyzed by nuclear magnetic resonance and liquid chromatography-mass spectrometry (LC-MS). The major product of oxidation of ERGO by hydrogen peroxide in physiological conditions was identified as hercynine (histidine betaine). One molecule of ERGO was able to reduce 2 molecules of hydrogen peroxide. Hercynine was found to react with the more potent oxidant hypochlorite. One unstable decomposition product was detected by LC-MS. As a result, a mechanism of oxidation of ERGO, and hence its physiological antioxidant activity, was developed.

Postnatal nutrition environment reprograms renal DNA methylation patterns in offspring of maternal protein-restricted stroke-prone spontaneously hypertensive rats.

Maternal malnutrition hampers the offspring health by manipulating the epigenome. Recent studies indicate that the changes in DNA methylation could be reversed by afterbirth nutrition supplementation. In this study, we used DNA methylation arrays to comprehensively investigate the DNA methylation status of the renal promoter regions and the effects of postnatal protein intake on DNA methylation. We fed stroke-prone spontaneously hypertensive (SHRSP) rat dams a normal diet or a low-protein diet during pregnancy, and their 4-week-old male offspring were fed a normal diet or a high-/low-protein diet for 2 weeks. We found that the methylation status of 2,395 differentially methylated DNA regions was reprogrammed, and 34 genes were reset by different levels of postnatal protein intake in the offspring. Among these genes, Adora2b, Trpc5, Ar, Xrcc2, and Atp1b1 are involved in renal disease and blood pressure regulation. Our findings indicate that postnatal nutritional interventions can potentially reprogram epigenetic changes, providing novel therapeutic and preventive epigenetic targets for salt-sensitive hypertension.