Tiancimycins (TNMs) are a group of 10-membered anthraquinone-fused enediynes, newly discovered from Streptomyces sp. CB03234. Among them, TNM-A and TNM-D have exhibited excellent antitumor performances and could be exploited as very promising warheads for the development of anticancer antibody-drug conjugates (ADCs).However, their low titers, especially TNM-D, have severely limited following progress.Therefore, the streptomycin-induced ribosome engineering was adopted in this work for strain improvement of CB03234, and a TNMs high producer S. sp. CB03234-S with the K43N mutation at 30S ribosomal protein S12 was successfully screened out. Subsequent media optimization revealed the essential effects of iodide and copper ion on the production of TNMs, while the substitution of nitrogen source could evidently promote the accumulation of TNM-D, and the ratio of produced TNM-A and TNM-D was responsive to the change of carbon and nitrogen ratio in the medium. Further amelioration of the pH control in scaled up 25 L fermentation increased the average titers of TNM-A and TNM-D up to 13.7 ± 0.3 and 19.2 ± 0.4 mg/L, respectively. The achieved over 45-fold titer improvement of TNM-A, and 109-fold total titer improvement of TNM-A and TNM-D enabled the efficient purification of over 200 mg of each target molecule from 25 L fermentation. Our efforts have demonstrated a practical strategy for titer improvement of anthraquinone-fused enediynes and set up a solid base for the pilot scale production and preclinical studies of TNMs to expedite the future development of anticancer ADC drugs.
An efficient method has been described to synthesize 1,3-dienes by cleaving the CC bond of enaminones with cyclopropenes under very mild reaction conditions, including low rhodium catalyst-loading, ambient temperature, and a neutral solvent system.
A series of BiOF/BiOCl x Br 1−x composites with different BiOF contents have been synthesized by means of ultrasonicassisted alcoholysis for the first time. The as-prepared samples were characterized by such methods as XRD, SEM, TEM, EDS, Mapping, BET, UV-Vis, XPS and PL spectra. The photocatalytic activity of samples under visible-light irradiation was evaluated by the degradation of Rhodamine. The results revealed that BiOF/BiOCl 0.75 Br 0.25 composite exhibited much higher photocatalytic activity than pure BiOF and BiOCl 0.75 Br 0.25 . And the 30%BiOF/BiOCl 0.75 Br 0.25 composite displayed the highest photocatalytic performance, reaching up 97% after irradiating with visible light for 45 min. The improvement of photocatalytic activity could be ascribed to the increased visible light absorption, its larger specific surface area and the enhanced electron-hole pairs effective separation. Moreover, the•O 2 − and h + were considered as the main active species during photocatalytic process. At last, the possible mechanism of the photocatalytic property was proposed in this paper.
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