Activation of microglia plays a crucial role in immune and inflammatory processes after ischemic stroke. Microglia is reported with two opposing activated phenotypes, namely, classic phenotype (M1) and the alternative phenotype (M2). Inhibiting M1 while stimulating M2 has been suggested as a potential therapeutic approach in the treatment of stroke. In this study, we indicated that a novel natural anti-oxidant extracted from the Chinese plant Hopea hainanensis, malibatol A (MA), decreased the infarct size and alleviated the brain injury after mice middle cerebral artery occlusion (MCAO). MA inhibited expression inflammatory cytokines in not only MCAO mice but also lipopolysaccharide (LPS)-stimulated microglia. Moreover, treatment of MA decreased M1 markers (CD16, CD32, and CD86) and increased M2 markers (CD206, YM-1) while promoting the activation of nuclear receptor PPARγ. MA has anti-inflammatory effects in MCAO mice in a PPARγ-dependent manner, making it a potential candidate for stroke treatment.

Genome mining targeting unique type II PKS and NRPS led to the identification of a novel class of glycopeptides named kitacinnamycins.

The ever-increasing bacterial genomic repositories reveal a great number of uncharacterized biosynthetic gene clusters, representing a tremendous resource for natural product discovery. Genome mining of the marine Streptomyces sp. NA03103 indicates the presence of an orphan nonribosomal peptide synthetase (NRPS) gene cluster (asm), to which there are no homologous gene clusters in the public genome databases. Heterologous expression of the asm gene cluster in the S. lividans SBT18 strain led to the discovery of two novel cyclopeptides, ashimides A and B (1 and 2), with 2 showing cytotoxic activity. In addition, we use bioinformatic analysis, gene inactivation and stable isotope labelling experiments, as well as in vitro biochemical assays, to present a coherent and novel assembly line for ashimide biosynthesis, featuring an unusual desaturation, halogenation and cyclization cascade catalyzed by a P450 monooxygenase and a FAD-dependent halogenase.