Curcuminoids are natural phenylpropanoids that are biosynthesized via an L-phenylalanine metabolism pathway in turmeric (Curcuma longa L.). Curcuminoids have various chemopreventive activities and pharmaceutical applications in human life. In this study, we synthesized dicinnamoylmethane, one principal component of curcuminoids, from cinnamic acid by means of co-expression of Oryza sativa curcuminoid synthase and Petroselinum crispum 4-coumarate-CoA ligase in Escherichia coli BL21 (DE3). Moreover, we used CRISPRi systems to knock down the genes in a tricarboxylic acid cycle and fatty acid biosynthesis pathway. The repression of target genes led to an increase of up to 0.236 μmol g DCW of malonyl-CoA in cytosol-engineered E. coli and subsequently increased the biosynthesis of dicinnamoylmethane. We found that the S10 strain containing a CRISPRi repression for three genes, fabF, fabD, and mdh, showed the highest amount of dicinnamoylmethane of 7.54 μM, which is 5.76-fold higher than that of the wild-type strain. Finally, 41.94 μM (~ 11.6 mg) of dicinnamoylmethane was obtained in a 3-L fermenter.
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http://dx.doi.org/10.1007/s12010-019-03206-8 | DOI Listing |
ACS Infect Dis
December 2024
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Carbapenemase producing (CPEs) represent a group of multidrug resistant pathogens for which few, if any, therapeutics options remain available. CPEs generally harbor plasmids that encode resistance to last resort carbapenems and many other antibiotics. We previously performed a high throughput screen to identify compounds that can disrupt the maintenance and replication of resistance conferring plasmids through use of a synthetic screening plasmid introduced into K-12 cells.
View Article and Find Full Text PDFCommun Biol
December 2024
Yunnan Provincial Key Laboratory of Animal Nutrition and Feed, Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, China.
Flagella are essential for biofilm formation, adhesion, virulence, and motility. In this study, the deletion of argR resulted in defects in flagellar synthesis and reduced motility, nevertheless, the underlying mechanism by which ArgR regulated bacterial motility remained unclear. ChIP-Seq and RNA-Seq analysis revealed that ArgR regulated the expression of flagellar genes, concluding two-component system flrBC and multitudinous flagellar structure genes.
View Article and Find Full Text PDFJ Infect Public Health
December 2024
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address:
Background: Currently, antimicrobial agents are widely used in both animals and agriculture, causing the crisis of multidrug-resistant (MDR) bacteria. In this study we surveyed for 4 important antimicrobial-resistant bacteria: extended-spectrum β-lactamase (ESBL)-producing Escherichia coli, Klebsiella pneumoniae and Salmonella spp., and methicillin-resistant Staphylococcus aureus (MRSA) from the environment around chicken and pig farms.
View Article and Find Full Text PDFBioorg Chem
December 2024
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address:
Given the ever-evolving landscape of antimicrobial resistance, the emergence of New Delhi metallo-β-lactamase-1 (NDM-1) has introduced a formidable challenge to global public health. In previous research, we identified the Compound Zndm19 as an NDM-1 inhibitor and reported Zndm19 derivatives, which exhibited moderate antibacterial activity when combined with meropenem (MEM). This moderate activity may have been due to the inability of Zndm19 to efficiently penetrate the bacterial outer membrane or its susceptibility to hydrolysis, which prevented it from exerting strong enzyme inhibition in synergy with bacterial cells.
View Article and Find Full Text PDFACS Nano
December 2024
Aix Marseille Univ, INSERM, SSA, MCT, 27 Bd Jean Moulin, Marseille 13005, France.
Bacterial resistance is a major public health challenge. In Gram-negative bacteria, the synergy between multidrug efflux pumps and outer membrane impermeability determines the intracellular concentration of antibiotics. Consequently, it also dictates antibiotic activity on their respective targets.
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