An NADPH-Dependent Ketoreductase Catalyses the Tetracyclic to Pentacyclic Skeletal Rearrangement in Chartreusin Biosynthesis.

Redox tailoring enzymes play key roles in generating structural complexity and diversity in type II polyketides. In chartreusin biosynthesis, the early 13 C-labeling experiments and bioinformatic analysis suggest the unusual aglycone is originated from a tetracyclic anthracyclic polyketide. Here, we demonstrated that the carbon skeleton rearrangement from a linear anthracyclic polyketide to an angular pentacyclic biosynthetic intermediate requires two redox enzymes. The flavin-dependent monooxygenase ChaZ catalyses a Baeyer-Villiger oxidation on resomycin C to form a seven-membered lactone. Subsequently, a ketoreductase ChaE rearranges the carbon skeleton and affords the α-pyrone containing pentacyclic intermediate in an NADPH-dependent manner via tandem reactions including the reduction of the lactone carbonyl group, Aldol-type reaction, followed by a spontaneous γ-lactone ring formation, oxidation and aromatization. Our work reveals an unprecedented function of a ketoreductase that contributes to generate structural complexity of aromatic polyketide.

Hyoid-complex elevation and stimulation technique restores swallowing function in patients with lateral medullary syndrome: Two case reports.

BACKGROUND: A swallowing disorder may occur following a brainstem stroke, especially one that occurs in the swallowing centers. Lateral medullary syndrome (referred to as LMS), a rare condition in which a vascular event occurs in the territory of the posterior inferior cerebellar artery or the vertebral artery, has been reported to lead to more severe and longer lasting dysphagia. CASE SUMMARY: We report two patients with dysphagia due to LMS and propose a novel technique named hyoid-complex elevation and stimulation technique (known as HEST). The two patients had no other functional incapacity back into life, but nasogastric feeding was the only possible way for nutrition because of severe aspirations. Swallowing function was evaluated by functional oral intake scale, modified water swallow test, surface electromyographic signal associated with video fluorography swallowing study to assess the situation of aspiration, pharyngeal residue, pharyngeal peristalsis, upper esophageal opening and the ability of deglutition. Both patients were treated with the HEST method for dysphagia and recovered quickly. CONCLUSION: HEST is effective for shortening the in-hospital time and improving the quality of life for patients with dysphagia who suffer from LMS and likely other strokes.