Chirality plays a critical role in the biochemistry of life and often only one enantiomeric series is observed (homochirality). Only a few natural products have been obtained as racemates, e.g. the signalling molecule valdiazen produced by Burkholderia cenocepacia H111. In this study, we investigated the ham biosynthetic gene cluster and discovered that both the enantiomerically pure (R)-fragin and the racemic valdiazen result from the same pathway. This stereodivergence is based on the unusual heterocyclic intermediate dihydrosydnone N-oxide, as evident from gene knockout, stable isotope feeding experiments, and mass spectrometry experiments. Both non-enzymatic racemisation via keto-enol tautomerisation and enzyme-mediated dynamic kinetic resolution were found to be crucial to this stereodivergent pathway. This novel mechanism underpins the production of configurationally and biologically distinct metabolites from a single gene cluster. Our findings highlight the intricate design of an intertwined biosynthetic pathway and provide a deeper understanding of microbial secondary metabolism related to microbial communication.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659414 | PMC |
Plant Cell Rep
December 2024
Institute of Nanfan & Seed Industry, Guangdong Academy of Sciences, Guangzhou, 510000, Guangdong, China.
A total of 24 genes of vacuolar H-translocating pyrophosphatases H-PPases (VPP) genes were identified in Saccharum spontaneum AP85-441 and the ScVPP1-overexpressed Arabidopsis plants conferred salt tolerance. The vital role of vacuolar H-translocating pyrophosphatases H-PPases (VPP) genes involved in plants in response to abiotic stresses. However, the understanding of VPP functions in sugarcane remained unclear.
View Article and Find Full Text PDFCefiderocol (FDC), a siderophore-cephalosporin conjugate, is the newest option for treating infection with carbapenem-resistant gram-negative bacteria. We identified a novel mechanism contributing to decreased FDC susceptibility in Klebsiella pneumoniae clinical isolates. The mechanism involves 2 coresident plasmids: pKpQIL, carrying variants of bla carbapenemase gene, and pKPN, carrying the ferric citrate transport (FEC) system.
View Article and Find Full Text PDFEvolution
December 2024
School of Biological Sciences, Institute of Ecology and Evolution, Edinburgh, UK.
Most studies investigating the genomic nature of species differences anticipate monophyletic species with genome-wide differentiation. However, this may not be the case at the earliest stages of speciation where reproductive isolation is weak and homogenising gene flow blurs species boundaries. We investigate genomic differences between species in a postglacial radiation of eyebrights (Euphrasia), a taxonomically complex plant group with variation in ploidy and mating system.
View Article and Find Full Text PDFHematology
December 2025
Department of Hematology, Shaoxing Shangyu people's Hospital, Shaoxing, People's Republic of China.
Objective: Liquid-liquid phase separation (LLPS) may affect the therapeutic sensitivity of multiple myeloma (MM). This study aimed to identify LLPS-related genes with MM prognostic values and to confirm their effects on tumor progression.
Methods: Based on public transcriptomic data, this study screened LLPS- and immune-related genes for MM-derived plasma cells.
Stat Interface
February 2024
Department of Statistics, Texas A&M University, College Station TX 77843, USA.
The development of modern sequencing technologies provides great opportunities to measure gene expression of multiple tissues from different individuals. The three-way variation across genes, tissues, and individuals makes statistical inference a challenging task. In this paper, we propose a Bayesian multi-way clustering approach to cluster genes, tissues, and individuals simultaneously.
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