Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory,
anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid
(MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using
Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing
the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced
the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation,
and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional
downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs.
model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1β (IL-1β; 76.4%, low-dose MG vs. model),
and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through
the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds
from medicinal plants.
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Our recent genome-based study indicated that Mycobacterium paragordonae (Mpg) has evolved to become more adapted to
an intracellular lifestyle within free-living environmental amoeba and its enhanced intracellular survival within Acanthamoeba
castellanii was also proved. Here, we sought to investigate potential use of Mpg for antimycobacterial drug screening
systems. Our data showed that Mpg is more susceptible to various antibiotics compared to the close species M. marinum
(Mmar) and M. gordonae, further supporting its intracellular lifestyle in environments, which would explain its protection
from environmental insults. In addition, we developed two bacterial whole-cell-based drug screening systems using a
recombinant Mpg stain harboring a luciferase reporter vector (rMpg-LuxG13): one for direct application to rMpg-LuxG13
and the other for drug screening via the interaction of rMpg-LuxG13 with A. castellanii. Direct application to rMpg-LuxG13
showed lower inhibitory concentration 50 (
IC50) values of rifampin, isoniazid, clarithromycin, and ciprofloxacin against
Mpg compared to Mmar. Application of drug screening system via the interaction of rMpg-LuxG13 with A. castellanii also
exhibited lower IC50
values for rifampin against Mpg compared to Mmar. In conclusion, our data indicate that Mpg is more
susceptible to various antibiotics than other strains. In addition, our data also demonstrate the feasibility of two whole cellbased
drug screening systems using rMpg-LuxG13 strain for the discovery of novel anti-mycobacterial drugs.
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Dhh1 and Dhh1 homologues (RCK/p54/DDX6) are mem-bers of the DEAD-box protein family of RNA helicases. These proteins display conserved sequence motifs for ATPase and RNA binding activities. Dhh1 is a component of the P-bodies (processing bodies) of mRNA granules and functions as an mRNA decapping activator in Saccharomyces cerevisiae. Dhh1 also contributes to gene-specific regulation during yeast mating. The dhh1 deletion mutation results in a significant decrease in the expression of Ste12, a mating-specific trans-cription factor, showing severe mating defects. Here, we in-troduced amino-acid substitution mutations in the ATPase and RNA binding domains of Dhh1 and also constructed a deletion of 79 amino acids at the Q/P-rich C-terminal region. The mutations in ATPase A and B motif (K96R, D195A) and C-terminus deletion showed reduced levels of mating effi-ciency as well as Ste12 protein expression. The Q/P-rich C- terminal region of Dhh1 was dispensable for growth at non- permissive temperature 37°C but appeared to play an im-portant role in regulating the Ste12 protein expression and mating processes. The P-body accumulation induced by treatment with α-mating factor required ATPase, RNA-bind-ing and the Q/P-rich C-terminal domains of Dhh1.
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Functional association of Loc1 and Puf6 with RNA helicase Dhh1 in translational regulation of Saccharomyces cerevisiae Ste12 Daehee Jung, Jong Seok Seo, Jayoung Nam, Jinmi Kim, Enrico Baruffini PLOS ONE.2019; 14(7): e0220137. CrossRef
Roles of eIF4E-binding protein Caf20 in Ste12 translation and P-body formation in yeast Kiyoung Park, Yu-Seon Lee, Daehee Jung, Jinmi Kim Journal of Microbiology.2018; 56(10): 744. CrossRef