scholarly journals EFFECTS OF 8-AZAGUANINE ON RIBOFLAVIN PRODUCTION AND ON THE NUCLEOTIDE POOLS IN NON-GROWING CELLS OF EREMOTHECIUM ASHBYII

1973 ◽  
Vol 19 (3) ◽  
pp. 215-227 ◽  
Author(s):  
Hisateru MITSUDA ◽  
Kenji NAKAJIMA
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joonas A. Jamsen ◽  
Akira Sassa ◽  
Lalith Perera ◽  
David D. Shock ◽  
William A. Beard ◽  
...  

AbstractReactive oxygen species (ROS) oxidize cellular nucleotide pools and cause double strand breaks (DSBs). Non-homologous end-joining (NHEJ) attaches broken chromosomal ends together in mammalian cells. Ribonucleotide insertion by DNA polymerase (pol) μ prepares breaks for end-joining and this is required for successful NHEJ in vivo. We previously showed that pol μ lacks discrimination against oxidized dGTP (8-oxo-dGTP), that can lead to mutagenesis, cancer, aging and human disease. Here we reveal the structural basis for proficient oxidized ribonucleotide (8-oxo-rGTP) incorporation during DSB repair by pol μ. Time-lapse crystallography snapshots of structural intermediates during nucleotide insertion along with computational simulations reveal substrate, metal and side chain dynamics, that allow oxidized ribonucleotides to escape polymerase discrimination checkpoints. Abundant nucleotide pools, combined with inefficient sanitization and repair, implicate pol μ mediated oxidized ribonucleotide insertion as an emerging source of widespread persistent mutagenesis and genomic instability.


Fermentation ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 11
Author(s):  
Fernando Pérez-García ◽  
Arthur Burgardt ◽  
Dina R. Kallman ◽  
Volker F. Wendisch ◽  
Nadav Bar

Residual streams from lignocellulosic processes contain sugar mixtures of glucose, xylose, and mannose. Here, the industrial workhorse Corynebacterium glutamicum was explored as a research platform for the rational utilization of a multiple sugar substrate. The endogenous manA gene was overexpressed to enhance mannose utilization. The overexpression of the xylA gene from Xanthomonas campestris in combination with the endogenous xylB gene enabled xylose consumption by C. glutamicum. Furthermore, riboflavin production was triggered by overexpressing the sigH gene from C. glutamicum. The resulting strains were studied during batch fermentations in flasks and 2 L lab-scale bioreactors separately using glucose, mannose, xylose, and a mixture of these three sugars as a carbon source. The production of riboflavin and consumption of sugars were improved during fed-batch fermentation thanks to a dynamic inoculation strategy of manA overexpressing strain and xylAB overexpressing strain. The final riboflavin titer, yield, and volumetric productivity from the sugar mixture were 27 mg L−1, 0.52 mg g−1, and 0.25 mg L−1 h−1, respectively. It reached a 56% higher volumetric productivity with 45% less by-product formation compared with an equivalent process inoculated with a single strain overexpressing the genes xylAB and manA combined. The results indicate the advantages of dynamic multi strains processes for the conversion of sugar mixtures.


Oncogenesis ◽  
2017 ◽  
Vol 6 (6) ◽  
pp. e349-e349 ◽  
Author(s):  
A Y Hafez ◽  
J E Messinger ◽  
K McFadden ◽  
G Fenyofalvi ◽  
C N Shepard ◽  
...  

2004 ◽  
Vol 70 (10) ◽  
pp. 5769-5777 ◽  
Author(s):  
Catherine Burgess ◽  
Mary O'Connell-Motherway ◽  
Wilbert Sybesma ◽  
Jeroen Hugenholtz ◽  
Douwe van Sinderen

ABSTRACT This study describes the genetic analysis of the riboflavin (vitamin B2) biosynthetic (rib) operon in the lactic acid bacterium Lactococcus lactis subsp. cremoris strain NZ9000. Functional analysis of the genes of the L. lactis rib operon was performed by using complementation studies, as well as by deletion analysis. In addition, gene-specific genetic engineering was used to examine which genes of the rib operon need to be overexpressed in order to effect riboflavin overproduction. Transcriptional regulation of the L. lactis riboflavin biosynthetic process was investigated by using Northern hybridization and primer extension, as well as the analysis of roseoflavin-induced riboflavin-overproducing L. lactis isolates. The latter analysis revealed the presence of both nucleotide replacements and deletions in the regulatory region of the rib operon. The results presented here are an important step toward the development of fermented foods containing increased levels of riboflavin, produced in situ, thus negating the need for vitamin fortification.


Author(s):  
Tatsuya Kato ◽  
Junya Azegami ◽  
Mai Kano ◽  
Hesham A. El Enshasy ◽  
Enoch Y. Park

2011 ◽  
Vol 42 (3) ◽  
pp. 1093-1100 ◽  
Author(s):  
Gaby Tiemi Suzuki ◽  
Juliana Alves Macedo ◽  
Gabriela Alves Macedo

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