The cyclic depsipeptides ohmyungsamycin (OMS) A (1) and B (2), isolated from the marine-derived Streptomyces sp. SNJ042, contain two non-proteinogenic amino acid residues, β-hydroxy-l-phenylalanine (β-hydroxy-l-Phe) and 4-methoxy-l-tryptophan (4-methoxy-l-Trp). Draft genome sequencing of Streptomyces sp. SNJ042 revealed the OMS biosynthetic gene cluster consisting of a nonribosomal peptide synthetase (NRPS) gene and three genes for amino acid modification. By gene inactivation and analysis of the accumulated products, we found that OhmL, encoding a P450 gene, is an l-Phe β-hydroxylase. Furthermore, OhmK, encoding a Trp 2,3-dioxygenase homolog, and OhmJ, encoding an O-methyltransferase, are suggested to be involved in hydroxylation and O-methylation reactions, respectively, in the biosynthesis of 4-methoxy-l-Trp. In addition, the antiproliferative and antituberculosis activities of the OMS derivatives dehydroxy-OMS A (4) and demethoxy-OMS A (6) obtained from the mutant strains were evaluated in vitro. Interestingly, dehydroxy-OMS A (4) displayed significantly improved antituberculosis activity and decreased cytotoxicity compared to wild-type OMS A.

Ler, a homolog of H-NS in enteropathogenic Escherichia coli (EPEC), plays a critical role in the expression of virulence genes encoded by the pathogenic island, locus of enterocyte effacement (LEE). Although Ler acts as an antisilencer of multiple LEE operons by alleviating H-NS-mediated silencing, it represses its own expression from two LEE1 P1 promoters, P1A and P1B, that are separated by 10 bp. Various in vitro biochemical methods were used in this study to elucidate the mechanism underlying transcription repression by Ler. Ler acts through two AATT motifs, centered at position −111.5 on the coding strand and at +65.5 on the noncoding strand, by simultaneously repressing P1A and P1B through DNA-looping. DNA-looping was visualized using atomic force microscopy. It is intriguing that an antisilencing protein represses transcription, not by steric exclusion of RNA polymerase, but by DNA-looping. We propose that the DNAlooping prevents further processing of open promoter complex (RP O ) at these promoters during transcription initiation.DNA-bending | first phosphodiester bond formation | road block transcript

A new bicyclic macrolide, hamuramicin C (1), was isolated from Streptomyces sp. MBP16, a gut bacterial strain of the wasp Vespa crabro f lavofasciata. Its 22-membered macrocyclic lactone structure was determined by NMR and mass spectrometry. The relative configurations of hamuramicin C (1) were assigned by J-based configuration analysis utilizing 1 H rotating frame Overhauser effect spectroscopy and heteronuclear long-range coupling NMR spectroscopy. Genomic and bioinformatic analyses of the bacterial strain enabled identification of the type-I polyketide synthase pathway, which employs a trans-acyltransferase system. The absolute configurations of 1 were proposed based on the analysis of the sequences of ketoreductases in the modular gene cluster. Moreover, hamuramicin C (1) demonstrated significant inhibitory activity against diverse human cancer cell lines (HCT116, A549, SNU-638, SK-HEP-1, and MDA-MB-231).

Aucklandia lappa Decne., known as “Mok-hyang” in Korea, has been used for the alleviation of abdominal pain, vomiting, diarrhea, and stress gastric ulcers in traditional oriental medicine. We investigated the anti-inflammatory and antioxidative effects of the ethanol extract of Aucklandia lappa Decne. (ALDE) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. ALDE significantly inhibited the LPS-induced nitric oxide (NO) production and reduced inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. The production of other proinflammatory mediators, including COX-2, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, was reduced by ALDE in LPS-stimulated RAW 264.7 cells. The mechanism underlying the anti-inflammatory effects of ALDE was elucidated to be the suppression of LPS-induced nuclear translocation of p65, followed by the degradation of IκB and the inhibition of the phosphorylation of mitogen-activated protein kinases (MAPK). In addition, ALDE showed enhanced radical scavenging activity. The antioxidant effect of ALDE was caused by the enhanced expression of heme oxygenase (HO-1) via stabilization of the expression of the nuclear transcription factor E2-related factor 2 (Nrf2) pathway. Collectively, these results indicated that ALDE not only exerts anti-inflammatory effects via the suppression of the NF-κB and MAPK pathways but also has an antioxidative effect through the activation of the Nrf2/HO-1 pathway.

Spinal cord injuries (SCI) are well thought to be a crucial issue that roots various side effects for a patient during their entire lifetime. Although therapeutical methods to resolve the SCI are limited, stem cell therapy is determined to be a resolving factor since it possesses the ability to induce the neurogenic differentiation and the paracrine effect. However, stem cells are difficult to inject directly into the lesion, so they must be carefully guided through the spinal canal. Therefore, superparamagnetic iron oxide nanoparticles (SPIONs) are introduced as an instigator that makes the cells respond to the applied magnetic field. This study intends to report the synthesis strategy to develop SPIONs that could be used to treat the injury site by an applied magnetic field. SPION-internalized D1 Mesenchymal stem cells (MSCs) are observed consistently using a confocal fluorescence microscope to analyze the toxicity, maintenance, and monitoring points of intracellular SPIONs. The prepared SPIONs are much anticipated to increase the migration efficiency using magnetism, which was not cytotoxic. Hence, the prepared SPIONs can adeptly target the damaged neural tissue to promote tissue regeneration and treat nervous system disorders. This primary study stands as a focal point to solve SCI by stem cell migration effectively.