A wide range of chemicals can be sensed by allosteric transcription factors (aTFs) in bacteria. Herein, we report a biosensing platform by using isolated aTFs as recognition elements in vitro. Moreover, a general strategy to increase the sensitivity of the aTF-based biosensors is provided. As a proof-of-concept, we obtained by far the most sensitive uric acid and oxytetracycline biosensors by using aTF HucR and OtrR as recognition elements, respectively. As a large number of aTFs are present in bacteria, our work opens a novel route to develop sensitive aTF-based biosensors.
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http://dx.doi.org/10.1039/c6cc07244e | DOI Listing |
Nat Commun
January 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China.
Oxidative stress plays a critical role in postmenopausal osteoporosis, yet its impact on osteoblasts remains underexplored, limiting therapeutic advances. Our study identifies phospholipid peroxidation in osteoblasts as a key feature of postmenopausal osteoporosis. Estrogen regulates the transcription of glutathione peroxidase 4 (GPX4), an enzyme crucial for reducing phospholipid peroxides in osteoblasts.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Biochemistry, University of Zurich, Winterthurerstrass 190, 8057 Zurich, Switzerland.
Type III clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems (type III CRISPR-Cas systems) use guide RNAs to recognize RNA transcripts of foreign genetic elements, which triggers the generation of cyclic oligoadenylate (cOA) second messengers by the Cas10 subunit of the type III effector complex. In turn, cOAs bind and activate ancillary effector proteins to reinforce the host immune response. Type III systems utilize distinct cOAs, including cyclic tri- (cA3), tetra- (cA4) and hexa-adenylates (cA6).
View Article and Find Full Text PDFNat Chem Biol
January 2025
Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA.
Cell-free systems are powerful synthetic biology technologies that can recapitulate gene expression and sensing without the complications of living cells. Cell-free systems can perform more advanced functions when genetic circuits are incorporated. Here we expand cell-free biosensing by engineering a highly specific isothermal amplification circuit called polymerase strand recycling (PSR), which leverages T7 RNA polymerase off-target transcription to recycle nucleic acid inputs within DNA strand displacement circuits.
View Article and Find Full Text PDFNat Commun
January 2025
Biophysics Program, Stanford University, Stanford, CA, USA.
Understanding how proteins discriminate between preferred and non-preferred ligands ('selectivity') is essential for predicting biological function and a central goal of protein engineering efforts, yet the biophysical mechanisms underpinning selectivity remain poorly understood. Towards this end, we study how variants of the promiscuous transcription factor (TF) MAX (H. sapiens) alter DNA specificity and selectivity, yielding >1700 Ks and >500 rate constants in complex with multiple DNA sequences.
View Article and Find Full Text PDFJ Med Chem
January 2025
Foghorn Therapeutics, 500 Technology Square, Suite 700, Cambridge, Massachusetts 02139, United States.
BRM (SMARCA2) and BRG1 (SMARCA4) are mutually exclusive ATPase subunits of the mSWI/SNF (BAF) chromatin remodeling complex. BAF is an attractive therapeutic target because of its role in transcription, and mutations in the subunits of BAF are common in cancer and neurological disorders. Herein, we report the discovery of compound () as a potent allosteric inhibitor of the dual ATPase subunits from a high-throughput screening hit with a BRM IC of ∼27 μM.
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