Nine new (1−3, 5−8, 11, and 12; named filipins VI−XIV) and three known (4, 9, and 10) filipin-type polyene macrolides were isolated from the deep-sea-derived Streptomyces antibioticus OUCT16-23 using a genome-guided strategy coupled with bioassay. Their structures were elucidated based on the extensive MS and NMR spectroscopic analyses together with ECD calculations. In an antifungal assay, compounds 4, 5, and 7−10 showed different degrees of growth inhibition against Candida albicans with minimum inhibitory concentrations (MICs) of 1.56−12.5 μg/mL, by which the alkyl side-chain substitution affecting the activity was preliminarily studied. A biosynthetic pathway to 1−12 in S. antibioticus OUCT16-23 is also proposed.
Exploration of unstable compounds is a rarely explored area of natural product research. We describe the integration of genomic and metabolomic analyses with bioassay-guided compound mining to effectively explore unstable bacillaenes. New bacillaene structures (2, 4, and 5) were identified from compound mixtures using the DANS-SVI (differential analysis of 2D NMR spectrum−single spectrum with variable intensities) method, which were further verified by the isolation of the pure compounds under strictly controlled conditions. Compound 1 exhibited antibacterial activity against multi-drug-resistant bacterial strains, while glycosylation decreased the activity of the bacillaene scaffold.
During spacecraft missions in some countries all over the world, a number of failures have been observed that were due to the lower reliability of thermal protection of launch vehicles, so the reliability of base heating prediction and thermal protection is very important for successful emissions. The thermal protection of launch vehicles is usually carried out according to the base heating prediction. The base heating environment is a complicated combination of exhaust plume radiation, reversed plume flow convective heating, and engine nozzle radiation. In this paper, the numerical analysis of base heating is performed to improve the precision of the predictive analysis, and then the flow is modeled using a two-dimensional, Reynolds averaged, and compressible Naive-Stokes equations and DSMC for a chemically frozen mixture gas. After that, the radiation is modeled by using RMC. On the basis of this elaborate base heating prediction, the weaknesses of the thermal protection can be found and the elaborate thermal protection can be realized, so the reliability of base heating prediction and thermal protection methodology can be increased.
Aims: Ebosin, a novel exopolysaccharide (EPS) produced by Streptomyces sp. 139 has antagonistic activity for interleukin‐1 receptor (IL‐1R) in vitro and remarkable anti‐rheumatic arthritis activity in vivo. Ebosin biosynthesis gene (ste) cluster has been identified in our laboratory. This paper reports our effort to characterize the function of ste11 gene.
Methods and Results: After the ste11 gene was cloned and expressed in Escherichia coli BL21, the recombinant Ste11 was purified and found capable of catalyzing NAD+ and l‐threonine to NADH and 2‐amino‐3‐ketobutyrate, hence identified as a threonine dehydrogenase (TDH). To investigate its function in the biosynthesis of Ebosin, the ste11 gene was knocked out with a double crossover via homologous recombination. The monosaccharide composition of EPS produced by the mutant strain (EPS‐m) was altered from that of Ebosin. The analysis of IL‐1R antagonist activity for EPSs showed that the bioactivity of EPS‐m was lower than Ebosin.
Conclusions: ste11 gene encoding a TDH may function as a modifier gene of Ebosin during its biosynthesis.
Significance and Impact of the Study: TDH encoded by ste11 is functional in Ebosin biosynthesis. It is the first characterized TDH in Streptomyces.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.