Chemogenetic engineering of nitrobindin toward an artificial epoxygenase

Author(s):  
Daniel Friedrich Sauer ◽  
Malte Wittwer ◽  
Ulrich Markel ◽  
Alexander Minges ◽  
Markus Spiertz ◽  
...  

Chemogenetic engineering of metalloproteins emerges as a powerful strategy to generate proteins that catalyze non-natural reactions or convert non-natural substrates. Here, we report on an artificial metalloenzyme (ArM) based on...

Author(s):  
Steven Banik ◽  
Kayvon Pedram ◽  
Simon Wisnovsky ◽  
Nicholas Riley ◽  
Carolyn Bertozzi

<p>Targeted protein degradation is a powerful strategy to address the canonically undruggable proteome. However, current technologies are limited to targets with cytosolically-accessible and ligandable domains. Here, we designed and synthesized conjugates capable of binding both a cell surface lysosome targeting receptor and the extracellular domain of a target protein. These lysosome targeting chimeras (LYTACs) consist of an antibody fused to agonist glycopeptide ligands for the cation-independent mannose-6-phosphate receptor (CI-M6PR). LYTACs enabled a CRISPRi knockdown screen revealing the biochemical pathway for CI-M6PR-mediated cargo internalization. We demonstrated that LYTACs mediate efficient degradation of Apolipoprotein-E4, epidermal growth factor receptor (EGFR), CD71, and programmed death-ligand 1 (PD-L1). LYTACs represent a modular strategy for directing secreted and membrane proteins for degradation in the context of both basic research and therapy. <b></b></p>


2019 ◽  
Vol 20 (7) ◽  
pp. 756-762 ◽  
Author(s):  
Aditi Kaushik ◽  
Manish Kaushik ◽  
Viney Lather ◽  
J.S. Dua

An emerging crisis of antibiotic resistance for microbial pathogens is alarming all the nations, posing a global threat to human health. The production of the metallo-&#946;-lactamase enzyme is the most powerful strategy of bacteria to produce resistance. An efficient way to combat this global health threat is the development of broad/non-specific type of metallo-&#946;-lactamase inhibitors, which can inhibit the different isoforms of the enzyme. Till date, there are no clinically active drugs against metallo- &#946;-lactamase. The lack of efficient drug molecules against MBLs carrying bacteria requires continuous research efforts to overcome the problem of multidrug-resistance bacteria. The present review will discuss the clinically potent molecules against different variants of B1 metallo-&#946;-lactamase.


Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2299
Author(s):  
Jéssica P. Silva ◽  
Alonso R. P. Ticona ◽  
Pedro R. V. Hamann ◽  
Betania F. Quirino ◽  
Eliane F. Noronha

Lignocellulosic residues are low-cost abundant feedstocks that can be used for industrial applications. However, their recalcitrance currently makes lignocellulose use limited. In natural environments, microbial communities can completely deconstruct lignocellulose by synergistic action of a set of enzymes and proteins. Microbial degradation of lignin by fungi, important lignin degraders in nature, has been intensively studied. More recently, bacteria have also been described as able to break down lignin, and to have a central role in recycling this plant polymer. Nevertheless, bacterial deconstruction of lignin has not been fully elucidated yet. Direct analysis of environmental samples using metagenomics, metatranscriptomics, and metaproteomics approaches is a powerful strategy to describe/discover enzymes, metabolic pathways, and microorganisms involved in lignin breakdown. Indeed, the use of these complementary techniques leads to a better understanding of the composition, function, and dynamics of microbial communities involved in lignin deconstruction. We focus on omics approaches and their contribution to the discovery of new enzymes and reactions that impact the development of lignin-based bioprocesses.


ACS Catalysis ◽  
2021 ◽  
pp. 6343-6347
Author(s):  
Sandro Fischer ◽  
Thomas R. Ward ◽  
Alexandria D. Liang

2017 ◽  
Vol 28 (2) ◽  
pp. 458-462 ◽  
Author(s):  
Jia-Ming Liu ◽  
Xing-Yu Liu ◽  
Xu-Shun Qing ◽  
Ting Wang ◽  
Cun-De Wang

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