Monthly Archives: March 2020

Bacteria: Friend or Foe?

Posted on March 23, 2020 by | 1 comment

Did you know that not all bacteria is bad? In some cases, they cause diarrhea, stomach ulcers, and even intestinal diseases. However, what if I told you scientists have found a way to manufacture antibiotics that are used to treat these bacterial infections from bacteria themselves?

Scanning Electron Microscope view of bacteria. Retrieved from: NYTIMES

Dr. Jason Hedges and Dr. Katherine Ryan of the University of British Columbia took a look into finding new enzymatic pathways for synthesizing nitroimidazole, which is a component in the antibiotic, azomycin.

So what is the point of this whole process and why do we even want to use bacteria to synthesize antibiotics?

By finding more ways to develop antibiotics from bacteria, this improves our knowledge on biosynthetic pathways. This is beneficial not only for the scientific community, but for the public as well. As bacteria develop resistances to antibiotics over time, the discovery of new antibiotics would be able to treat more patients suffering from bacterial infections.

How is this done?

Now how could something that sounds so complex be done? Let us take a look at their process step-by-step.

Like all scientists do, background research was performed to see how previous scientists went about finding ways to develop antibiotics from bacteria. To do so, a bioinformatics search was performed. Bioinformatics is essentially ‘googling’ information about a certain topic, but in this case, they would be using a scientific database such as the National Centre for Biotechnology Information (NCBI).

A cryptic gene cluster was found in the bacterial strain Streptomyces cattleya. This along with various enzymes were the main points of interest. Their goal was to use L-arginine; a fundamental building block of proteins, and find a way to convert this into nitroimizadole (a component of the antibiotic, azomycin

Theoretically, a blueprint on how L-arginine would be converted to nitroimidazole was developed. However, experiments must be conducted to see if the pathway would work in real life, and not just on paper.

Figure 1 – Biosynthetic pathway towards nitroimidazole. Retrieved from: Hedges and Ryan, 2019

Through experimentation, the pathway as shown in figure 1 was deemed to have synthesized nitroimidazole successfully. The next step was to determine whether or not azomycin could be synthesized from Streptomyces cattleya. Unfortunately, they were unsuccessful in detecting any levels of nitroimidazole in the bacteria samples. They concluded that potentially a different molecule had been synthesized, or that this specific gene cluster is silent (inactivate).

Although Hedges and Ryan were unable to find a definitive pathway to synthesizing azomycin utilizing bacteria, their work was able to disprove aa few reaction schemes in the scientific community, allowing for further research to be conducted.

Science is not always about success. In science, you must fail in order to succeed. Their work provides a stepping stone into further scientific research such a finding other biosynthetic pathways in the synthesis of other antibiotics.

 

Literature Cited:

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

-Jackson Kuan

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Assemble Sugars with the Assistance of a “Secret Weapon”—Enzyme

Posted on March 23, 2020 by | Leave a comment

People eat sugar every day, but do you know scientists can make whatever types of sugar they want? A group of researchers led by Dr Stephen Withers from the University of Columbia found an efficient method for creating new sugars. They selected a powerful type of biological catalyst called enzymes, which can assemble certain types of sugar molecules faster and cleaner than other chemical catalysts. This method has potential applications in drug development for diseases such as diabetes and obesity.

Sugars are referred to as a type of molecules that consist of units of hydrocarbons assembled in a long chain. The picture below shows various sugar molecules. Each hexagon represents a sugar unit, and different sugars have different numbers of units. Sugars with only one unit are called monosaccharides. Glucose and fructose are common monosaccharides. Our table sugar has one glucose combined with one fructose and is called disaccharide (of course!). Polysaccharides consist of starch, cellulose, and glycogen (sugar stored in your body). Sugars also exist on the cell surface and act as the receptor for many drug molecules. Therefore, knowing the properties of different sugars and how to synthesize them is an essential topic in modern biology and chemistry.

Figure 1. Sugar in daily life vs. Sugar in chemistry

Despite sugars are important to human, making the desired type of sugar molecules is a tricky problem. The reason is that many sugar units have a unique geometry. To maintain the biological functions of sugars, we also need to keep its original shape. Most of the synthetic chemical methods can assemble the sugar unit in the desired order, but cannot retain the geometry. To solve this problem, Withers and his group decided to use a “secret weapon” in biology—enzymes.

Enzymes are a special type of proteins widely existing in all organisms. They can accelerate the chemical reactions in our body and sustain normal metabolic processes. More importantly, enzymes are highly specific to particular sugar geometry. In other words, they only react with sugars that fit their structures and yield product that also has one specific structure. The type of enzymes accelerates sugar assembly is called glycosynthase, and the type accelerates disassembly is called glycoside hydrolase. Now, using enzymes seem to be promising, but where to find the enzymes we want?

To find the desired enzyme more quickly, scientists used a technique called metagenomics which allows them to sample the genes of millions of microorganisms without the need for individual culture. Instead of directly searching for enzymes that can link the sugar together, the first step is to find enzymes (glycoside hydrolase) which break sugar bond (Surprise!). Researchers used bacteria as factories to produce the enzymes and collect them together. Of course, we want enzyme glycosynthase that LINK sugar bonds. The next step is to reconstruct those enzymes such that they can assemble the sugar correctly. Researchers change the reaction centre of the glycoside hydrolase by muting some of the critical structures. By doing so, some of the glycoside hydrolases betrayed their original duties and started to assemble the sugar unit. Figure 2 shows the overall procedures for the experiment.

Abstract Image

Figure 2. Experimental procedure. Sugars are shown as chair-like hexagons. The aim is to link the sugars to various substrate molecules (shown in different colours).

Eventually, Withers and his group found eight types of enzymes that are specific to the assembly of different sugar molecules, which is almost impossible using traditional methods. As discussed before, sugars construct the receptors for drug and other signal molecules in our body. Understanding how to synthesize sugar will help scientists build new medicines targeted to specific body cells. Diseases such as diabetes and obesity that are related to sugars will also be better understood in the future.

Reference:

Armstrong, Z.; Liu, F.; Chen, H.-M.; Hallam, S. J.; Withers, S. G. Systematic Screening of Synthetic Gene-Encoded Enzymes for Synthesis of Modified Glycosides. ACS Catalysis 2019, 9 (4), 3219–3227.

https://pubs.acs.org/doi/abs/10.1021/acscatal.8b05179

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Characterizing Asthma Attacks Using Gene Expression

Posted on March 23, 2020 by | Leave a comment

Analyzing gene expression levels can be a way to distinguish patients with severe and non-severe asthma. Lower rRNA expression levels of histone deacetylase 2 (HDAC2), (erythroid-derived 2)-like 2 (Nrf2), and glucocorticoid-induced transcript 1 (GLCCI1) are observed in severe asthma patients compared to non-severe patients. These low levels indicate asthma exacerbation happens more frequently in severe asthma patients.

5-10% of people with asthma are affected with severe asthma. A study in 2019 examined HDAC2, Nrf2, and GLCCI1 genes to compare their mRNA expression levels with severe and non-severe asthma patients. In all 3 genes, lower expression levels is observed in severe asthma patients, as seen in Figure 1.

Fig 1. (A) mRNA expression levels of GLCCI1, Nrf2, and HDAC2 for severe and non-severe asthma (B) Receiver operating characteristic for the discrimination between severe and non-severe asthma (Retrieved from: Hirai)

Samples were retested if the variations were greater than 5%. With a 95% confidence interval and p values less than 0.05, indicating statistical significance, the coefficients were calculated for all 3 genes.

Patients were re-evaluated after 1 year to identify exacerbations that may occur. It was shown that exacerbations occurred in 44% of severe asthma patients and only 9.4% of non-severe asthma patients. This is directly related to the mRNA expression levels. Patients with a much lower expression level are more likely to have asthma exacerbations.

These results can be quantified to predict future exacerbation. This helps with the amount of corvicalsteroids needed for treatment. This is especially important for severe asthma patients, as corvicalsteroids are less effective compared to non-severe patients.

Observing gene expression is a method to distinguish between severe and non-severe asthma patients. It can help with reducing exacerbations using appropriate treatment.

-Wilson Wong

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Eat with your… Environment?

Posted on March 22, 2020 by | 1 comment

We have all heard about eating with our eyes first, but no one ever talks about how our environment affects our meals. Mother Nature Network (MNN) indicate that your environment plays big factor in your perception of food. Whether it’s lighting, furniture, or noise, they all play a role.

Figure 1 – Chocolate Ice Cream Retrived from: HandletheHeat

This study published in October 2019 explored temporal changes in how chocolate ice cream was perceived when eaten at different locations. Each participant had their electrophysisological properties, emotions, and temporal changes in flavour monitored, with 5 minute breaks inbetween each measurement. The participants were randomly assigned different environments such as a university study area, a bus stop, a cafe, or a sensory testing laboratory.

Figure 2 – The 4 locations in which tests were conducted. A – Sensory testing laboratory B – University study area C – Bus stop D – Cafe Retrieved from: Figure 2 of Xu et al.

Electrophysiological Responses

3 electrophysiological responses were measured, including skin conductance (SC), blood volume pulse (BVP), and heart rate (HR). They found that SC and HR was significantly influenced by different environments. Using the Tukey-Kramer test, they found that eating chocolate ice cream in the study space compared to the laboratory significantly increases SC (F(3,156) = 3.149, p < 0.05). Furthermore, the HR was significantly lower after consumption in the study area compared to a bus stop (F(3,156) = 2.673, p < 0.05).

Figure 3 – Electrophysiological response measurements. n= 160 (50 males/110 females) Retrieved from: Figure 10 Xu et al.

Emotional Response

In a pilot study, the emotional responses were reported among 97 individuals. Positive emotions were noted such as happiness, cheerfulness, and joy. In addition, negative emotions were noted as well, such as tenseness, unhappiness, and anxiousness. Using a Cochran Q-test, they found that a significant number of negative emotions were associated with the bus stop compared to the other 3 environments. Furthermore, a significant number of positive emotions were expressed after consuming chocolate ice cream at a cafe or university compared to a bus stop.

Figure 4 – Both positive and negative emotions associated with eating chocolate ice cream in 4 different environments. Data adapted from: Xu et al.

Taste

The dominance of different attributes were measured and converted to a percentage of time it spent as a dominant factor. Sweetness the dominant attribute across all environments (46% lab, 33% university, 48% cafe, 38% bus stop). Interestingly, the dominance of sweetness subsided overtime, and other attributes became dominant. Other factors such as creaminess, roastedness, and bitterness was noted as well. At the bus stop, bitterness became the most dominant factor after sweetness, while the other 3 locations reported either creaminess, cocoa, or vanilla flavours were dominant.

How do I improve my next meal?

Next time you’re at the dinner table, try some of these tricks to improve the taste of your meal. By listening to higher pitched music, sour and sweet flavours are highlighted, while lower pitched music enhances bitter flavours. Even something as simple as the way food is arranged on the plate will impact its flavour.

-Jackson Kuan

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Orvig Group at UBC Creates Novel Molecule for Diagnostic Nuclear Medicine

Posted on March 22, 2020 by | Leave a comment

You may be aware of the role physicists and doctors play in diagnostic nuclear medicine, however you may not know that chemists also play a significant role in this area of science!

In 2019, Chris Orvig of the Medicinal Inorganic Chemistry Group at the University of British Columbia (UBC) created a new organic molecule for medical imaging. They also determined that their novel organic molecule has superior properties to similar molecules currently being used.

The molecule created by the inorganic chemistry group at UBC is simply known as H2hox, a hexadentate chelating ligand. What exactly does that mean? Let’s break it down piece-by-piece.

A ligand is a type of molecule that can bind onto a metal ion, like sodium (Na+) or calcium (Ca2+). In the case of H2hox, the metal ion it’s binding to is Gallium (Ga3+) because it is used in medical imaging.

The word chelating comes from the latin root word chela, which means claw. This is because chelating ligands have multiple points of attachment to a metal ion, similar to a crab’s claw, making them significantly stronger binders to metal ions.

The word hexadentate comes from the latin root words hexa, which means six and dent, which means tooth. So a hexadentate chelating ligand has six attachment points, or teeth, that can grab onto a desired metal ion.

Image sources (left to right): Research Gate, Orvig et al..

 

So why is H2hox used in medical imaging?

Molecules such as H2hox are used in a form of medical imaging known as Positron-emission tomography (PET). John Hopkins Medicine defines PET imaging as “using a scanning device (a machine with a large hole at its center) to detect photons (subatomic particles) emitted by a radionuclide in the organ or tissue being examined”.

PET imaging is primarily used to diagnose health issues related to biochemical processes occurring inside our cells, such as cancer. The radionuclide, or radioactive atom, of choice for H2hox is Gallium ions. Since ions alone cannot be used in imaging, due to their poor mobility through our cells and tissues, they are packaged together with small organic molecules, such as H2hox, before injection into human tissue.

So what makes H2hox better than the current available options?

H2hox is an advantageous ligand for Gallium PET medical imaging because…

  • It can be easily synthesized (made) through only 1 reaction step.
  • It has a strong affinity to Gallium, exhibiting significant radiolabeling (binding to Ga3+) in only 5 minutes with low amounts of ligand and under mild conditions (room temperature)
  • The combined ligand and ion have excellent stability in vitro (inside cells) and in vivo (inside a beaker).

These combined properties make H2hox an effective and convenient molecule for Gallium PET imaging. Furthermore, Orvig’s research will act as a launching-off point for the development of even better ligands to improve the quality and ease of PET imaging and diagnosis.

I hope this news article educated you about medicinal inorganic chemistry through describing its role in medical imaging.

 

Literature cited:

Wang, X.; De Guadalupe Jaraquemada-Peláez, M.; Cao, Y.; Pan, J.; Lin, K. S.;                       Patrick, B. O.; Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic                       Chelating Ligand for 68Ga Radiopharmaceuticals. Inorg. Chem.                                 [Online] 2019, 58, 2275-2285.                                                                                          https://pubs.acs.org/doi/10.1021/acs.inorgchem.8b01208 (accessed                      March 22, 2020).

 

-Mark Rubinchik

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The Power of Acceptance

Posted on March 22, 2020 by | Leave a comment

When life throws us curveballs, we’re often told to hit them out of the park. However, in a recent study, researchers at Yale University found that when individuals were presented with negative stimuli, those who merely accepted their situations experienced less pain and unpleasant emotion than those who reacted naturally to the stimuli.

First, the researchers introduced participants to the concept of mindfulness, which practices the acceptance of a situation. Then, participants were placed in two different groups: one subject to high heat on the forearm, and the other subject to negative images.

Through brain scans, the team observed that participants who practiced mindfulness had reduced activity in regions of the brain concomitant to pain response and negative emotion upon stimuli compared to those who reacted. Furthermore, the participants self-reported that they experienced significantly less negative affects when they accepted their situations.

Figure 1. Participants (n=16) experienced more negative affects upon seeing negative vs. neutral images (a), and upon feeling hot vs. warm temperatures (b) when they chose to react instead of accepting. The * indicates p<0.05, *** indicates p<0.0001, and error bars indicate standard error. (Credits: Kober et al. (2020))

Mindfulness is already practiced by patients suffering from chronic pain and depression, but these findings show the power that acceptance has even on individuals who have never meditated, and the team believes that mindfulness is a good way to temporarily regulate the intensity of pain and negative emotions.

HOW DOES MINDFULNESS WORK?

Scientists are still unsure of how meditation elicits responses in the brain; perhaps mindfulness allows us to feel more in control of our circumstances when we’re having negative experiences, or it reminds us that we have enough strength to make it through whatever. Nonetheless with this technique added to our repertoire, the next time life throws us a curveball we will be more prepared to deal with it.

-Athena Wang

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Microwave misconceptions: What actually happens when food is heated?

Posted on March 21, 2020 by | Leave a comment

There are several misconceptions regarding microwave ovens, many of which are simply not true. In fact, one of the most abstract claims made about microwaves is that they can cause cancer. As scientists, we understand that this is not the case. Microwave ovens exploit high wavelength radiation at the lower energy region of the electromagnetic spectrum, which is not particularly dangerous. It is thus important to dispel some of the misconceptions regarding microwave ovens, especially the myths about radioactivity and poor protection.

SEATTLE, WA – SEPTEMBER 20: An “Amazonbasics Microwave,” which can be controlled by Alexa, is pictured at Amazon Headquarters shortly after being launched, on September 20, 2018, in Seattle Washington. Amazon launched more than 70 Alexa-enable products during the event. (Photo by Stephen Brashear/Getty Images)

Radioactive species are not generated in a microwave oven

Radioactivity involves the emission of radiation from spontaneous decay of unstable atomic nuclei. Energy is lost through the release of elementary particles, such as gamma-ray photons, from the nucleus or from electron shells as x-rays. Fortunately, microwave ovens do not release these high energy species, nor do they produce such high energy species. Most microwaves use a magnetron to generate either pulsed or continuous microwaves. In the magnetron, beams of electrons are made to follow curved trajectories, in vacuum tubes, through the combination of electric and magnetic fields. The consumer microwave magnetron emits 2.45 GHz microwaves. This frequency is quite low, which corresponds to low energy. What this means is microwaves do not have enough energy to remove electrons from the food being heated. What they will do is generate heat by inducing molecular vibrations, breaking hydrogen bonds, and allowing for ionic migration of free salts in an electric field.

Microwave ovens are well protected

While the microwave door might seem simple, it is actually inherently complicated. Many different components are used to form the protective door. One of those pieces is known as a choke. In a study conducted by Kusama et al., it was found that the structure of the choke derived in a finite-difference time-domain (FDTD) analysis was very similar to the experimentally designed choke structure. This structure was also found to obtain the maximum shielding effect. While there were many parameters and factors, they assessed the metal lengths (S1 and S2) and the angle (theta). They calculated the radiation power P2 exiting the choke by changing the three previously mentioned parameters. One rather interesting finding from their paper was the effect of the angle on the shielding. This portion was conducted at fixed metal lengths of 4.00 mm and 9.01mm for S1 and S2 respectively.

Angle (theta)[Deg] 0 15.52 26.56 33.69 45.00 56.31 63.40 70.56 90
Approximate Shielding effect [dB] 21 18 27 35 29 22 18 17 16

From the data, it is evident that the shielding length changed with the angle, and the optimum angle was found to be 33.69o. This theoretical structure (S1 4 mm, S2 9.01 mm,  33.69o) was found to resemble the empirical structure, and thus the choke has been designed shield effectively. Hence, the choke and other components, which reflect microwave radiation, provide apt protection and prevent the release.

Don’t believe everything you read online; Microwaves are safe. Let me know what your opinions are in the comments.

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LEGO: Is it more than just a kids toy?

Posted on March 21, 2020 by | 4 comments

With everyone staying at home due to recent events, a common struggle is finding ways to pass the time. You remember having a box of LEGO bricks lying around, but you think to yourself “Building with LEGO? Nah, that’s just a kid’s toy!”. However, LEGO bricks are more than just a construction toy, they are also a technological marvel both in manufacturing and function.

The LEGO group first patented their iconic LEGO brick design in 1958 in Billund, Denmark. Modern LEGO bricks are made of ABS plastic, a copolymer of acrylonitrile, 1,3-butadiene and styrene, which is formed into its distinct brick-like shape using the injection molding process.  The molds are designed to produce LEGO pieces accurate to up to five-thousandth of a millimeter (0.005 mm), which is around half the thickness of a human hair. This results in a piece defect rate of 0.0018%. In other words, the LEGO manufacturing process produces 18 defective pieces out of every 1 million total pieces produced.

Left to right: Structures of styrene, acrylonitrile and 1,3-butadiene, the main components that make up the plastic used to make LEGO bricks. Source: Sigma-Aldrich

LEGO bricks have become an iconic construction toy due to the endless building possibilities they present. LEGO bricks are connected together through round nubs on top of the brick, known as studs, to tube-based cavities on the bottom of the brick. For instance, six LEGO bricks that are two studs wide by four studs long, commonly referred to as a 2×4 brick, can be combined in 915,103,765 unique ways. This number was determined computationally by mathematics professor  Søren Eilers from the University of Copenhagen in 2005.

(Photo credit: Mark Rubinchik)

Although a LEGO brick may seem like a simple piece of plastic, there is a lot more to it than meets the eye. Next time you’re looking for something to do, why not pull out some LEGO and see how many combinations you can make!

-Mark Rubinchik

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Vaccination and Herd Immunity

Posted on March 21, 2020 by | 2 comments

Herd immunity is often generated through vaccination or widespread infection. For the current Covid-19 pandemic, many scientists and experts advocate social distancing to avoid overwhelming hospitals while buying more time for the inventions of vaccines and treatments. Why is vaccination favored by scientists and medical experts than a widespread infection? How is herd immunity achieved through vaccination?

What is herd immunity?

Herd immunity refers to a means of protecting a whole community from disease by immunizing a critical portion of its populace. Vaccination protects the vaccinated person but also the people who are not immunized. However, to achieve herd immunity, we need a certain percentage of people in a community to be vaccinated.

Herd immunity, the result of a high immunization rate. Source: The National Institute of Allergy and Infectious Disease (NIAID)

To reach the herd immunity threshold, different vaccination coverages which depend on the basic reproduction number (Ro) are required. Vaccination coverage is the estimated percentage of people who have received specific vaccines. For example, measles, a highly contagious virus, has a Ro value between 12 and 18. This high Ro value calls for a high vaccine coverage which is 92-94%. In other words, to reach the herd immunity threshold, at least 92% of the population needs to be vaccinated.

The higher the vaccine coverage the better…

Does it mean that measles will die out as long as 92% of the population is vaccinated against measles? The answer is no. Dr. Plans-Rubio, an epidemiology expert in Europe, found a significant negative correlation (P<0.05) between the incidence of measles in 2017–2018 in different countries of the European Union and measles vaccination coverage with herd immunity levels in the target measles vaccination population during 2015–2017. According to Dr. Plans-Rubio, low percentages of measles vaccination coverage with two doses of vaccine and the resulting low herd immunity levels explained measles incidence and persistence of measles in the European Union in 2017-2018. To eliminate the measles virus in the European Union, W.H.O must improve routine measles vaccination coverage and conduct supplementary measles vaccination campaigns.

Linear correlation coefficient p
Coverage with two doses of measles vaccine − 0.533 0.003
Coverage with one dose of measles vaccine 0.523 0.004
Coverage with first dose of measles vaccine − 0.332 0.079
Coverage with second dose of measles vaccine − 0.559 0.002
Prevalence of individuals with vaccine-induced measles protection (Iv) − 0.580 0.001
Herd immunity gap (94.5 − Iv)a − 0.580 0.001

(Table source: European Journal of Clinical Microbiology & Infectious Diseases)

Relating to Covid-19 pandemic

Without measles vaccines, we would not have lowered the mortality rate of measles and reached herd immunity in most countries. The novel coronavirus, similar to measles, is also contagious. To lower the mortality rate of Covid-19 and reach herd immunity, the corresponding vaccine is required. Hence, every single one of us should practice social distancing to avoid overwhelming our healthcare system while scientists strive to invent the corresponding vaccine.

 

Reference:

Plans-Rubio Pedro. Low percentages of measles vaccination coverage with two doses of vaccine and low herd immunity levels explain measles incidence and persistence of measles in the European Union in 2017–2018. European Journal of Clinical Microbiology & Infectious Diseases, 2019; 38, 1719-1729. DOI: https://link-springer-com.ezproxy.library.ubc.ca/article/10.1007%2Fs10096-019-03604-0#Sec2

-Pricia

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Sugar Chemistry: A Pathway to Antibiotics

Posted on March 18, 2020 by | 1 comment

We’ve all heard it endlessly as kids. Don’t eat too much sugar, it’s bad for you. However, what if I told you that sugars aren’t all that bad and in fact, careful changes to its chemistry can lead to life-saving drugs, such as antibiotics! Just last year, researchers at the University of British Columbia, led by Stephen Withers, found a unique way to tinker with sugars’ chemical structures by using molecules in bacteria. The same bacteria found in our poop!

A view of E. Coli, the bacteria that was used by Wither’s and his team. Credits: The Philadelphia Inquirer

Sweet…but what are they?

Before we go further, let’s start with a simple question: What exactly are sugars? Sugars are molecules shaped like hexagons which are often joined to other molecules known as “acceptors”. In a way we are kind of like sugars; we find someone we like, confess how we feel, and they accept our love! Right? Wrong. As we all know the last part rarely happens and this is the same in sugars, as chemists have yet to find easy ways to join the sugar and acceptors. Luckily for sugars (and unluckily for us), Mother Nature has come up with some solutions, using helper molecules known as enzymes.

Curious as to what type of sugars chemists work with? There’s no ambiguity here, chemists use the same molecules found in sugar cubes. Yes! The ones you put in your coffee. Credits: The Verge

a solution under our noses…

Instead of struggling to find ways of joining sugars and acceptors, Wither’s team thought: Why not just use these enzymes? In other words, hijack Mother Nature. To make their idea a reality, they extracted sugar-specific enzymes from E. Coli, a bacterium that lives inside the human digestive tract. Their efforts gave them 175 sugar-specific enzymes, and from this they chose 8 enzymes that were most specific to the type of sugars and acceptors they were interested in.

“With the 8 enzymes in hand, Withers and his team could now easily make these sugar-acceptor linkages” is what I would like to report; however, things are never so simple. It turns out that the sugar-specific enzymes they got from E. Coli did the exact opposite of what they wanted. Instead of forming sugar-acceptor linkages, they were specialized in breaking them.

Unsurprisingly the savvy researchers expected this and already had a reliable strategy to reverse-engineer these enzymes from linkage breakers to linkage makers. You may be wondering how they re-purposed something to work completely opposite of what it was intended for. To reconcile this, think of this example: hammers. If you’re feeling angry one day you would likely use the hammer to smash things. However, if you’re feeling innovative one day, the hammer would help you build things by hammering in nails. These enzymes are similar; an enzyme that breaks sugar bonds differs very little from one that builds sugar bonds.

more than just a bond…

Sugars go way beyond than just satisfying your sugar fix. They are molecules essential to the maintenance and regulation of not only your body, but in most living things! Because they are found everywhere, including infectious bacteria, sugar-based molecules serve as effective antibiotics, however making these drugs are difficult. Why? Well as mentioned before, chemists have trouble making these sugar-acceptor bonds; however, the research done by Wither’s team show that this will not remain the case. On a lighter note, they also created a sugar-based molecule that had nothing to do with health; detergent. This just further shows that these bonds are far-reaching and relevant in many contexts.

Story source

Armstrong, Z.; Liu, F.; Chen, H.-M.; Hallam, S. J.; Withers, S. G. Systematic Screening of Synthetic Gene-Encoded Enzymes for Synthesis of Modified Glycosides. ACS Catalysis 2019, 9 (4), 3219–3227.

-Kenny Lin

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Posted in Biological Chemistry, Chemistry News, Organic Chemistry