Polymerization of nucleic acids in biology utilizes 5'-nucleoside triphosphates (NTPs) as substrates. The prebiotic availability of NTPs has been unresolved and other derivatives of nucleoside-monophosphates (NMPs) have been studied. However, this latter approach necessitates a change in chemistries when transitioning to biology. Herein we show that diamidophosphate (DAP), in a one-pot amidophosphorylation-hydrolysis setting converts NMPs into the corresponding NTPs via 5'-nucleoside amidophosphates (NaPs). The resulting crude mixture of NTPs are accepted by proteinaceous- and ribozyme-polymerases as substrates for nucleic acid polymerization. This phosphorylation also operates at the level of oligonucleotides enabling ribozyme-mediated ligation. This one-pot protocol for simultaneous generation of NaPs and NTPs suggests that the transition from prebiotic-phosphorylation and oligomerization to an enzymatic processive-polymerization can be more continuous than previously anticipated.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1002/anie.202113625 | DOI Listing |
J Bacteriol
December 2024
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.
MutT proteins are Nudix hydrolases characterized by the presence of a Nudix box, GX5EX7REUXEEXGU, where U is a bulky hydrophobic residue and X is any residue. Major MutT proteins hydrolyze 8-oxo-(d)GTP (8-oxo-GTP or 8-oxo-dGTP) to the corresponding 8-oxo-(d)GMP, preventing their incorporation into nucleic acids. Mycobacterial MutT1 comprises an N-terminal domain (NTD) harboring the Nudix box motif, and a C-terminal domain (CTD) harboring the RHG histidine phosphatase motif.
View Article and Find Full Text PDFACS Synth Biol
December 2024
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Cell-free transcription-translation (TX-TL) systems have been used for diverse applications, but their performance and scope are limited by variability and poor predictability. To understand the drivers of this variability, we explored the effects of metabolic perturbations to an () Rosetta2 TX-TL system. We targeted three classes of molecules: energy molecules, in the form of nucleotide triphosphates (NTPs); central carbon "fuel" molecules, which regenerate NTPs; and magnesium ions (Mg).
View Article and Find Full Text PDFBiotechnol J
November 2024
Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, UK.
Following the recent COVID-19 pandemic, mRNA manufacturing processes are being actively developed and optimized to produce the next generation of mRNA vaccines and therapeutics. Herein, the performance of the tangential flow filtration (TFF) was evaluated for high-recovery, and high-purity separation of mRNA from unreacted nucleoside triphosphates (NTPs) from the in vitro transcription (IVT) reaction mixture. For the first time, the fouling model was successfully validated with TFF experimental data to describe the adsorption of mRNA on filtration membrane.
View Article and Find Full Text PDFFront Plant Sci
October 2024
Center for Biological Science and Technology, Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, Advanced Institute of Natural Sciences, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, China.
The addition of non-templated nucleotides at the 3' terminus of RNA is a pervasive and evolutionarily conserved posttranscriptional modification in eukaryotes. Apart from canonical poly(A) polymerases (PAPs), which are responsible for catalyzing polyadenylation of messenger RNAs in the nucleus, a distinct group of non-canonical PAPs (ncPAPs), also known as nucleotidyl transferase proteins (NTPs), mediate the addition of uridine and adenosine or of more intricate combinations of nucleotides. Among these, HEN1 SUPPRESSOR 1 (HESO1) and UTP: RNA URIDYLYLTRANSFERASE (URT1) are the two most extensively studied NTPs responsible for the addition of uridine to the 3' ends of RNAs (RNA uridylation).
View Article and Find Full Text PDFChemistry
October 2024
Department of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 6, 44227, Dortmund, Germany.
Organic chromophores have been successfully implemented into supramolecular systems to bestow them with distinct photophysical properties for various applications, ranging from solar energy conversion, photochemical reactions or as receptors for guest molecules with optical readout. We had previously introduced first members of the large family of coal-tar dyes (methylene blue, crystal violet and rhodamine) as integral components of coordination cages. Here, we add two new chromophores, malachite green (MGP) and a purple phenazinium dye (PHP), serving as backbones of bis-monodentate banana-shaped ligands with pyridine donors.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!