Discovery of undescribed anthracycline-derived polyketides with cytotoxicity from endophytic Streptomyces chartreusis M7.

Endophytic actinomycetes exhibit considerable potential for the production of biologically active metabolites due to their coevolution with plant hosts. In this study, an endophytic Streptomyces chartreusis M7 was isolated from Houttuynia cordata Thunb. Bioactivity-guided investigation of the metabolites produced by this strain led to the identification of thirteen anthracycline-derived polyketides, including five unreported anthraquinones designated streptoquinones A-E (1-5) and two undescribed angular polyketides named chartins A and B (6-7) along with six knowns.

Longitudinal course of hyperintensity on diffusion weighted imaging in adult-onset neuronal intranuclear inclusion disease patients.

Background: High signals on diffusion weighted imaging along the corticomedullary junction (CMJ) have demonstrated excellent diagnostic values for adult-onset neuronal intranuclear inclusion disease (NIID). However, the longitudinal course of diffusion weighted imaging high intensities in adult-onset NIID patients has rarely been investigated.

Methods: We described four NIID cases that had been discovered using skin biopsy and gene testing, after diffusion weighted imaging exhibiting the distinctive corticomedullary junction high signals.

Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation.

Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments.

Alteration of the Catalytic Reaction Trajectory of a Vicinal Oxygen Chelate Enzyme by Directed Evolution.

The vicinal oxygen chelate (VOC) metalloenzyme superfamily catalyzes a highly diverse set of reactions with the mechanism characterized by the bidentate coordination of vicinal oxygen atoms to metal ion centers, but there remains a lack of a platform to steer the reaction trajectories, especially for o-quinone metabolizing pathways. Herein, we present the directed-evolution-enabled bifunctional turnover of ChaP, which is a homotetramer and represents an unprecedented VOC enzyme class. Unlike the ChaP catalysis of extradiol-like o-quinone cleavage and concomitant α-keto acid decarboxylation, a group of ChaP variants (CVs) catalyze intradiol-like o-quinone deconstruction and CO liberation from the resulting o-hydroxybenzoic acid scaffolds with high regioselectivity.

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 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.

Molecular Basis for the Final Oxidative Rearrangement Steps in Chartreusin Biosynthesis.

Oxidative rearrangements play key roles in introducing structural complexity and biological activities of natural products biosynthesized by type II polyketide synthases (PKSs). Chartreusin (1) is a potent antitumor polyketide that contains a unique rearranged pentacyclic aromatic bilactone aglycone derived from a type II PKS. Herein, we report an unprecedented dioxygenase, ChaP, that catalyzes the final α-pyrone ring formation in 1 biosynthesis using flavin-activated oxygen as an oxidant.

Strepchazolins A and B: Two New Alkaloids from a Marine Streptomyces chartreusis NA02069.

Two new alkaloids, strepchazolins A () and B (), together with a previously reported compound, streptazolin (), were isolated from a marine actinomycete, NA02069, collected in the Coast of Hainan Island, China. The structures of new compounds were determined by extensive NMR, mass spectroscopic and X-ray crystallographic analysis, as well as modified Mosher's method. Compound showed weak anti- activity with the MIC value of 64.