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Insights into Heterocycle Biosynthesis in the Cytotoxic Polyketide Alkaloid Janustatin A from a Plant-Associated Bacterium.
Biochemistry
January 2025
Institute of Microbiology, Eidgenössische Technische Hochschule (ETH) Zurich, Vladimir-Prelog-Weg 4, 8093 Zurich, Switzerland.
Janustatin A is a potently cytotoxic polyketide alkaloid produced at trace amounts by the marine bacterial plant symbiont . Its biosynthetic terminus features an unusual pyridine-containing bicyclic system of unclear origin, in which polyketide and amino acid extension units appear reversed compared to the order of enzymatic modules in the polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) assembly line. To elucidate unknown steps in heterocycle formation, we first established robust genome engineering tools in .
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Región Metropolitana, Chile.
Background: The human brain integrity relies on the synergistic interplay between neural activity and supporting vascular and metabolic processes throughout life. This relationship, ruled by allostatic mechanisms, regulates brain architecture and activity. White matter hyperintensities (WMH) serve as indicators of the vascular impact on brain structure.
View Article and Find Full Text PDFBackground: Metabolic syndrome (MetS) has been previously associated with an increased risk of developing dementia. Exploring links between MetS, neuroimaging and cognitive function measures can offer insights into whether MetS adversely affects brain health prior to dementia onset. We sought to examine the association of MetS with brain structure and cognition.
View Article and Find Full Text PDFDeveloping Topics.
Alzheimers Dement
December 2024
University of California, San Francisco, San Francisco, CA, USA.
Background: An optimized 6 amino acid peptide (NLSYYT; herein YΦ) derived from the C-terminus of h19S proteasome activator Rpt5 has been shown to activate the 20S proteasome and promote tau degradation. Further analysis of this peptide has identified the highly conserved leucine in position 5 (P5) as a key part of the 20S activation mechanism to drive degradation of tau monomers in the absence of proteasome activator complexes.
Method: Recombinant peptides were used to identify key amino acids required for binding and activating the h20S proteasome.
Alzheimer's Imaging Consortium.
Alzheimers Dement
December 2024
Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibáñez, Santiago, Región Metropolitana, Chile.
Background: The human brain integrity relies on the synergistic interplay between neural activity and supporting vascular and metabolic processes throughout life. This relationship, ruled by allostatic mechanisms, regulates brain architecture and activity. White matter hyperintensities (WMH) serve as indicators of the vascular impact on brain structure.
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