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About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug development. So, methyltransferases catalyzing the methylation have always attracted great attention. Hangtaimycin (HTM) is a potent hepatoprotective agent. Previous study showed that its biosynthetic gene cluster contained three methyltransferase domains, but their characteristics in HTM biosynthetic pathway has not been revealed. In this study, we clarified multi-methylations in HTM biosynthesis in vivo. It showed that the two S-adenosylmethionine-dependent methyltransferases (SAM-MTs) of HtmA2(-module 6)-MT domain and HtmB2(-module 18)-MT domain are responsible for the installation of methyl group at C-45 and N-12, respectively, whereas the FK506 methyltransferase (FKMT) type O-methyltransferase of HtmB1(-module 16)-MT domain take care of the methylation at O-21 of HTM. We also reported the antibacterial activities of HTM in this study, and found that it showed activities against M. luteus, B. thuringiensis and A. baumannii with MIC of 4 μg/mL, 4 μg/mL, and 64 μg/mL, respectively.

All-dielectric metamaterials have recently received significant attention in the field of nanophotonics, due to their negligible dissipative losses and strong polariton response compared with metallic metamaterials. However, simultaneously achieving an ultra-narrow resonance linewidth and a significant field enhancement in the all-dielectric metamaterials is still a great challenge, limiting their further practical application. In this work, a novel nanostructure composed of silicon ring and nanodimer arrays is theoretically proposed and numerically simulated. Through introducing the coupling between the anapole mode originating from the ring arrays and the gap mode deriving from the nanodimer arrays, the as-designed dielectric metamaterial manifests dual-band high-quality resonance characteristics with strong electric field enhancement reaching up to 300 times, an ultra-narrow linewidth as narrow as 0.35 nm, and a large Q-factor of 4223.43 synchronously. Benefiting from the exceptional optical spectral characteristics, the proposed dielectric nanodimer-ring metamaterial can work as a high-available refractive index sensor, whose sensitivity can reach 307.69 nm RIU−1 with its figure of merit attaining 879.11 RIU−1, efficiently distinguishing an index change of less than 0.01. This research opens up a promising path for achieving extremely narrow spectral linewidth and significant enhancement of the electric field, exhibiting immense possibilities in applications such as biochemical sensing, nonlinear optics, and surface enhanced spectroscopy.

An improved synthesis for tryptophan-dehydrobutyrine diketopiperazine (TDD), a co-metabolite of the hybrid polyketide/non-ribosomal peptide hangtaimycin, starting from ʟ-tryptophan is presented. Comparison to TDD isolated from the hangtaimycin producer Streptomyces spectabilis confirmed its S configuration. The X-ray structure of the racemate shows an interesting dimerisation through hydrogen bridges. The results from bioactivity testings of hangtaimycin, TDD and the hangtaimycin degradation product HTM222 are given.

Streptovaricin C is an antibiotic containing a methylenedioxy bridge (MDB) moiety essential for its activity. Here, the authors show that a P450 monooxygenase StvP2 catalyses MDB formation, report its crystal structure in complex with the substrate, and elucidate mechanistic details of MDB formation.

Abstract Background Cancer stem cells (CSCs) are highly proliferative and tumorigenic, which contributes to chemotherapy resistance and tumor occurrence. CSCs specific therapy may achieve excellent therapeutic effects, especially to the drug-resistant tumors. Results In this study, we developed a kind of targeting nanoparticle system based on cationic albumin functionalized with hyaluronic acid (HA) to target the CD44 overexpressed CSCs. All-trans-retinoic acid (ATRA) was encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (EE%) of 93% and loading content of 8.37%. TEM analysis showed the nanoparticles were spherical, uniform-sized and surrounded by a coating layer consists of HA. Four weeks of continuously measurements of size, PDI and EE% revealed the high stability of nanoparticles. Thanks to HA conjugation on the surface, the resultant nanoparticles (HA-eNPs) demonstrated high affinity and specific binding to CD44-enriched B16F10 cells. In vivo imaging revealed that HA-eNPs can targeted accumulate in tumor-bearing lung of mouse. The cytotoxicity tests illustrated that ATRA-laden HA-eNPs possessed better killing ability to B16F10 cells than free drug or normal nanoparticles in the same dose, indicating its good targeting property. Moreover, HA-eNPs/ATRA treatment decreased side population of B16F10 cells significantly in vitro. Finally, tumor growth was significantly inhibited by HA-eNPs/ATRA in lung metastasis tumor mice. Conclusions These results demonstrate that the HA functionalized albumin nanoparticles is an efficient system for targeted delivery of antitumor drugs to eliminate the CSCs.

Cancer stem cells with stem-cell properties are regarded as tumor initiating cells. Sharing stem-cell properties, circulating tumor cells (CTCs) are responsible for the development of metastasis, which significant affects CTC analysis in clinical practice. Due to their extremely low occurrence in blood, however, it is challenging to enumerate and analyze CTCs. Nanotechnology is able to address the problems of insufficient capture efficiency and low purity of CTCs owing to the unique structural and functional properties of nanomaterials, showing strong promise for CTC isolation and detection. In this review, we discuss the role of stem-like CTCs in metastases, provide insight into recent progress in CTC isolation and detection approaches using various nanoplatforms, and highlight the role of nanotechnology in the advancement of CTC research. [ABSTRACT FROM AUTHOR]

A new butoxy substituted indolediketopiperazine (1), together with five known indolediketopiperazines (2-6), which are derivatives of brevianamides, were isolated from the marine derived fungus Aspergillus sp. 66may. Careful analysis and comparison of the HRESIMS, as well as 1D and 2D NMR datasets, identified the structures of the isolated compounds. The subsequent antibacterial and anti-inflammatory activities showed that compound 4 possessed antimicrobial bioactivities against Bacillus subtilis ATCC 39620 with minimum inhibitory concentration (MIC) value of 64 µg/mL. Compounds 1, 2, 4 exhibited potential inhibitory activities against NO production with IC50 value of 28.2, 21.3, 23.6 µM, respectively. It seems that butoxy substitution at C-9 in brevianamides have little effects on their antimicrobial and anti-inflammatory bioactivities. [ABSTRACT FROM AUTHOR]