Genomic and metabolomic profiling reveal Streptomyces rochei S32 contributes to plant growth by nitrogen fixation and production of bioactive substances

Author: Jiao, Mengfan ; Wei, Xiaomin ; Wang, Congcong ; Yu, Xingchi ; Wei, Miao ; Liu, Yutao ; Nie, Xibin

To unfold the full potential of plant growth-promoting rhizobacteria in crop production it is desirable to explore the mechanisms through which they promote growth.We investigated the potential mechanisms of plant growth promotion by Streptomyces rochei S32 in two crops.The effects of S. rochei S32 on plant growth and its antagonistic activity against soil-borne pathogenic fungi were tested.The underlying mol. mechanisms were identified based on whole-genome sequencing and bioinformatics anal.The results of genomic anal. were verified by widely targeted metabolomics and mechanism studies of plant growth promotion.S. rochei S32 significantly improved the growth of wheat and tomato.The shoot length (24.7%) and root length (25.3%) of wheat (400-fold dilution of cell-free fermentation filtrate) were increased, and the root length of tomato (200-fold dilution) was prolonged (40.9%), and the field yield was also increased.S. rochei S32 showed antagonistic activity against multiple pathogenic fungi, especially Macropoma kawatsukai.The bacterial genome contains an 8,041,158-bp chromosome and two plasmids.A total of 7486 annotated genes were classified into 31 Gene Ontol. functional categories.Genomic anal. revealed the potential for the production of indole-3-acetic acid, fungal cell wall hydrolases, antibiotics (e.g., candicidin, streptothricin, borrellin, albaflavenone), and siderophores.Thirty-nine phytohormones and 2205 secondary metabolites were detected, including indole-3-acetic acid, phytosphingosine, acivicin, and corynebactin.Normal bacterial growth occurred on a nitrogen-free medium.S. rochei S32 can promote plant growth directly or indirectly through nitrogen fixation and production of phytohormones, extracellular hydrolases, antibiotics, and siderophores.

26 Jul 2024·Endocrinology

High-throughput Screening for Cushing Disease: Therapeutic Potential of Thiostrepton via Cell Cycle Regulation

Article

Author: Fujita, Haruka ; Kosugi, Daisuke ; Ueda, Yohei ; Sugawa, Taku ; Yamauchi, Ichiro ; Okamoto, Kentaro ; Fujii, Toshihito ; Hakata, Takuro ; Inagaki, Nobuya ; Taura, Daisuke

AbstractCushing disease is a life-threatening disorder caused by autonomous secretion of ACTH from pituitary neuroendocrine tumors (PitNETs). Few drugs are indicated for inoperative Cushing disease, in particular that due to aggressive PitNETs. To explore agents that regulate ACTH-secreting PitNETs, we conducted high-throughput screening (HTS) using AtT-20, a murine pituitary tumor cell line characterized by ACTH secretion. For the HTS, we constructed a live cell–based ACTH reporter assay for high-throughput evaluation of ACTH changes. This assay was based on HEK293T cells overexpressing components of the ACTH receptor and a fluorescent cAMP biosensor, with high-throughput acquisition of fluorescence images. We treated AtT-20 cells with compounds and assessed ACTH concentrations in the conditioned media using the reporter assay. Of 2480 screened bioactive compounds, over 50% inhibition of ACTH secreted from AtT-20 cells was seen with 84 compounds at 10 μM and 20 compounds at 1 μM. Among these hit compounds, we focused on thiostrepton (TS) and determined its antitumor effects in both in vitro and in vivo xenograft models of Cushing disease. Transcriptome and flow cytometry analyses revealed that TS administration induced AtT-20 cell cycle arrest at the G2/M phase, which was mediated by FOXM1-independent mechanisms including downregulation of cyclins. Simultaneous TS administration with a cyclin-dependent kinase 4/6 inhibitor that affected the cell cycle at the G0/1 phase showed cooperative antitumor effects. Thus, TS is a promising therapeutic agent for Cushing disease. Our list of hit compounds and new mechanistic insights into TS effects serve as a valuable foundation for future research.

24 Nov 2022·Journal of Biomolecular Structure and Dynamics

Virtual screening of quinoline derived library for SARS-COV-2 targeting viral entry and replication

Article

Author: Chaudhary, Vishakha ; Anju, Anju ; Mishra, Anil Kumar ; Chaturvedi, Shubhra ; Pant, Pradeep ; Hussain, Firasat

The COVID-19 pandemic infection has claimed many lives and added to the social, economic, and psychological distress. The contagious disease has quickly spread to almost 218 countries and territories following the regional outbreak in China. As the number of infected populations increases exponentially, there is a pressing demand for anti-COVID drugs and vaccines. Virtual screening provides possible leads while extensively cutting down the time and resources required for ab-initio drug design. We report structure-based virtual screening of a hundred plus library of quinoline drugs with established antiviral, antimalarial, antibiotic or kinase inhibitor activity. In this study, targets having a role in viral entry, viral assembly, and viral replication have been selected. The targets include: 1) RBD of receptor-binding domain spike protein S 2) M^pro Chymotrypsin main protease 3) P^pro Papain protease 4) RNA binding domain of Nucleocapsid Protein, and 5) RNA Dependent RNA polymerase from SARS-COV-2. An in-depth analysis of the interactions and G-score compared to the controls like hydroxyquinoline and remdesivir has been presented. The salient results are (1) higher scoring of antivirals as potential drugs (2) potential of afatinib by scoring as better inhibitor, and (3) biological explanation of the potency of afatinib. Further MD simulations and MM-PBSA calculations showed that afatinib works best to interfere with the the activity of RNA dependent RNA polymerase of SARS-COV-2, thereby inhibiting replication process of single stranded RNA virus. Communicated by Ramaswamy H. Sarma.

100 Deals associated with Haloprogin

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KEGG	Wiki	ATC	Drug Bank
D00339	Haloprogin	D01AE11	DB00793

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