Jia Song,Jinyu Qiao,Mingxue Chen,Jiahui Li,Jixia Wang,Dayong Yu,Huachuan Zheng,Liying Shi
Chaetoglobosin A (ChA) is an antitumor compound produced by Chaetomium globosum . However, the mechanism of its antitumor effect has been rarely reported. In this study, we evaluated the anti-proliferative effect of ChA on T-24 human bladder cancer cells and explored its mechanism of action. ChA was found to have a good inhibitory effect on T-24 cells by MTT assay with an IC50 value of 48.14 ± 10.25 μΜ. Moreover, it was found to have a migration inhibitory ability and a sustained proliferation inhibitory effect on tumor cells by cell aggregation assay and cell migration assay. The cells morphological changes were determined by Hoechst33342 assay. While Annexin V-FITC/PI double-staining assay also demonstrated that the number of apoptotic cells increased with the increase of drug concentration. Flow cytometry results showed that ChA treatment increased reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP) in T-24 cells and inhibited cell mitosis, resulting in an increase in the number of sub-G1 phase cells. Further western blot experiments demonstrated that MAPK and PI3K-AKT-mTOR pathways were activated after drug treatment in addition to endogenous and exogenous apoptotic pathways. The addition of the ROS inhibitor N-acetylcysteine (NAC) upregulated the expression level of Bcl-2 protein, decreased p38 phosphorylation, increased ERK phosphorylation and restored the levels of PI3K and p-mTOR after ChA treatment. These suggest that ChA induces apoptosis by regulating oxidative stress, MAPK, and PI3K-AKT-mTOR signaling pathways in T-24 cells.
Straw, an abundant lignocellulosic biomass, is a promising renewable feedstock for sustainable production of high-value antibiotics and polysaccharides. In this study, three differentially expressed genes, Cgedg , Cgxyl , and Cglac , were identified through transcriptomic sequencing and bioinformatic analysis, and overexpressed under the constitutive promoter oliC in Chaetomium globosum W7 to generate engineered strains for chaetoglobosin A (cheA) biosynthesis. Notably, the overexpression mutants cxlac10 and cxlac16 demonstrated superior degradation of cornstalk, achieving total removal rates of 39.23 % and 43.47 % after 9 days of incubation, respectively, significantly surpassing the performance of the wild-type strain. Furthermore, the activities of lignocellulose-degrading enzymes, including filter paper hydrolyzing cellulase, carboxymethyl cellulase, xylanase, and laccase, were notably enhanced in these strains. Scanning electron microscopy and Fourier transform-infrared spectroscopy revealed that these overexpression strains could effectively disrupt the recalcitrant lignocellulosic structure. Both cxlac10 and cxlac16 exhibited increased mycelial biomass and significantly enhanced cheA production, when compared with the wild-type strain, with cheA yields increasing from 42.59 mg/L to 209.70 and 217.76 mg/L, respectively. This study offers valuable insights and effective strategies for the bioconversion of lignocellulosic resources into bioactive polyketide alkaloids.
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