The complex environment of fungi requires a delicate balance between the efforts to acquire nutrition, to reproduce, and to fend off competitors. In , an interrelationship between regulation of enzyme gene expression and secondary metabolism was shown. In this study, we investigated the physiological relevance of the unique YPK1-type kinase USK1 of . is located in the vicinity of the SOR cluster and is involved in regulation of several genes from this secondary metabolite cluster as well as dihydrotrichotetronine and other secondary metabolites. Moreover, USK1 is required for biosynthesis of normal levels of secondary metabolites in liquid culture. USK1 positively influences cellulase gene regulation, secreted cellulase activity, and biomass formation upon growth in constant darkness on cellulose. Positive effects of USK1 on transcript abundance of the regulator of secondary metabolism, , and the carbon catabolite repressor gene are in agreement with these functions. In summary, we found that with USK1, comprises a unique kinase that adds an additional layer of regulation to the connection of secondary metabolism and enzyme production in fungi.
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http://dx.doi.org/10.3389/fmicb.2020.00974 | DOI Listing |
Orphanet J Rare Dis
January 2025
Division of Pediatric Epileptology, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University, Heidelberg, Germany.
Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760-1:13,520 live births in Germany. On the molecular level, TSC is caused by heterozygous loss-of-function variants in either of the genes TSC1 or TSC2, encoding the Tuberin-Hamartin complex, which acts as a critical upstream suppressor of the mammalian target of rapamycin (mTOR), a key signaling pathway controlling cellular growth and metabolism. Despite the therapeutic success of mTOR inhibition in treating TSC-associated manifestations, studies with mTOR inhibitors in children with TSC above two years of age have failed to demonstrate beneficial effects on disease-related neuropsychological deficits.
View Article and Find Full Text PDFNat Commun
January 2025
Institute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre Juelich, Juelich, Germany.
Targeting of diseased cells is one of the most urgently needed prerequisites for a next generation of potent pharmaceuticals. Different approaches pursued fail mainly due to a lack of specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting combined with selective expression of effector proteins for therapy, diagnostics or cell steering.
View Article and Find Full Text PDFHomozygous MTAP deletion occurs in ~15% of cancers, making them vulnerable to decreases in the concentration of S-adenosylmethionine (SAM). AG-270/S095033 is an oral, potent, reversible inhibitor of methionine adenosyltransferase 2 A (MAT2A), the enzyme primarily responsible for the synthesis of SAM. We report results from the first-in-human, phase 1 trial of AG-270/S095033 as monotherapy in patients with advanced malignancies (ClinicalTrials.
View Article and Find Full Text PDFBMJ Open
January 2025
National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) Center for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, England, UK
Introduction: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity.
View Article and Find Full Text PDFEnviron Pollut
January 2025
State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Heat stress disturbs cellular homeostasis and alters the fitness of individual organisms. However, it is unclear whether thermal perturbations exacerbate the toxic effects of per- and polyfluorinated alkyl substances (PFASs) on trophic endpoints in freshwater ecosystems. We conducted a mesocosm experiment to investigate the impact of warming and PFASs on the widespread submerged macrophytes (Hydrilla verticillata) at a molecular level.
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