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Abstract Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N-formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.5 Å apart unlike canonical FAD-dependent oxidoreductases. One site could accommodate glycine and the other glycinothricin or glycylthricin. Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. The chain length of nucleophilic acceptors vies with bond cleavage sites at either N–O or O–S accounting for N-formimidoylation or N-iminoacetylation. The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species.

Bacteria-derived polycationic homopoly(amino acid)s are reported for the first time to directly penetrate cell membrane and deliver proteins of interest into cells, representing a new type of cell penetrating peptides for intracellular delivery.

Abstract Although the incidence of hepatobiliary enzyme abnormality increased immediately after the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident, longer-term trends remain unclear. The aims of this study were to determine longer-term trends in hepatobiliary enzyme abnormality and to elucidate lifestyle factors associated with such changes among residents of a nuclear-disaster-affected area. This longitudinal survey enrolled 20,395 adults living in the vicinity of Fukushima Daiichi Nuclear Power Plant. Data were obtained from the records of annual health checkups of adults aged ≥40 years between 2011 and 2012. Follow-up examinations were conducted from June 2013 to March 2014. Associations were assessed between changes in hepatobiliary enzyme abnormality immediately and 3–4 years after the disaster and lifestyle factors. The overall prevalence of hepatobiliary enzyme abnormality significantly decreased over the study period, from 29.9% to 27.1%. Multivariate logistic regression analysis revealed significant associations between improved hepatobiliary enzyme abnormality and improvements in daily physical activity and frequency of breakfast consumption. The results suggest that improvements in daily physical activity and frequency of breakfast consumption significantly reduced the incidence of hepatobiliary enzyme abnormality 3–4 years after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident.