Research News – 4

There were many interesting articles published in the last three weeks. Some of them are inspiring in terms of experimental design while others clearly show the steep progress that has been made in synthetic biology.
1. Electric field increases enzyme activity: As reported in science: “Enzymes accelerate chemical processes by coaxing molecules into just the right reactive states. Fried et al. now elucidate the way the enzyme ketosteroid isomerase pushes its substrate toward product through exertion of a local electric field (see the Perspective byHildebrandt)”.
Relevance: Enzyme kinetics
2. Expanding the genetic code won 34% of votes from researchers who visited the website of Science Magazine (the first one went to the Comet probe). Editor of Nature writes: The genetic code is simple: four bases that form two pairs (A–T and G–C) are used in all of life. Expansion of this code to incorporate unnatural nucleotides and base pairing has been a goal of synthetic biology, as it would open up ways to tailor organisms for directed purposes. Although this has been achieved in proof-of-principle experiments in vitro, stable propagation of an expanded code had not been demonstrated in vivo until now. Floyd Romesberg and colleagues present evidence that two hydrophobic nucleotides, d5SICSTP and dNaMTP, can be added to the medium in which Escherichia coli expressing an exogenous algal nucleotide triphosphate transporter is growing, and that these nucleotides will be incorporated in the genome and are not recognized as lesions by the repair pathway. Consequently, the unnatural-base-pair-containing DNA is replicated, without cell growth being significantly affected.
Relevance: Sheer power of genetic manipulation

3. Protein design de novo: Scientists have accomplished an once considered difficult task. They have designed a membrane protein which can transport Zinc but not copper. The editor of Science writes: Enzymes are proteins that are the workhorses of the cell. Designing enzymes with new functions that are also manifested in living systems could be extremely valuable in bioengineering and synthetic biology applications. However, enzyme design is a challenging task and so far has mainly been restricted to repurposing natural enzymes and to in vitro systems. Song and Tezcan started with a monomeric redox protein and introduced mutations that cause it to assemble into a tetramer with catalytic zinc ions in its interfaces. This protein assembly displayed β-lactamase activity, the primary mechanism of antibiotic resistance, and enabled E. coli cells to survive ampicillin treatment. 
Relevance: Better protein design
4. Antibiotic discovery:  The editor of Nature writes: In a paper published on Nature’s website this week, a team ofresearchers announces the discovery of a brand new antibiotic Called (by them) teixobactin, the compound is produced by a specific type of soil bacterium — the cultivation of which was previously impossible (see also G. Wright Nature; 2015). There could be more undiscovered antibiotics out there. There could be lots more. 
Relevance: biodiversity
5. Glutathione and virulence: The editor of Nature writes: To successfully colonize their hosts, intracellular pathogens must be able to sense their environment and modulate virulence gene expression. For instance, when Listeria monocytogenes infects host cells, it remodels its transcriptional program through activation of the master regulator PrfA. Previous work has suggested that PrfA is allosterically regulated by a small molecule activator, specific to the host intracellular environment, but the identity of this small molecule has proven elusive. Here Daniel Portnoy and colleagues show that bacterial and host-derived glutathione is essential for L. monocytogenes pathogenesis, but not via its canonical role in redox homeostasis. Rather, glutathione activates PrfA by acting as the previously predicted allosteric modulator. 
Relevance: Glutathione plays a role in stress response in yeast. But in Listeria, it aids virulence.

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