Category Archives: Chemistry News

LIFE-SAVING IMPROVEMENTS To Blood Transfusions

Posted on April 10, 2020 by | Leave a comment

Have you ever ended up in the hospital and needed a blood transfusion? Well, that’s about to get a whole lot easier for people everywhere! An article published by Nature Microbiology in June 2019 by Dr. Stephen Withers, studied a new method in converting type A blood to the universal type O blood using bacteria found in the human gut! [1] 

A team led by Dr. Stephen Withers at the University of British Columbia has developed a method which would eliminate the need for blood-type compatibility, reducing the risks of blood transfusions.  

What are blood types? 

There are 8 different blood types, and before these findings, these blood types were not all compatible with each other. Each blood type can only receive from other specific types.  

In human bodies, there are 8 types of red blood cells. These types are determined by two factors: Blood Groups and Rh Factors. 

We have 4 different blood groups: A, B, AB and O, different blood groups carry different signals (see Image 1).O-type cells do not carry any signals.

 Similarly, Rh-positive red blood cells carry another signal, and Rh-negative cells carry nothing. Blood groups and Rh factors are combined, so that we have blood types such as A positive, O negative, etc.

Image depicting the different signals on red blood cells. Created by Eric Ding using PowerPoint.

If we transfuse  O negative cells, which do not carry any signals, they can be recognized by anyone with any type of blood. 

 However, if we transfuse A positive red blood cells to a patient with AB negative blood, the immune system can recognize the triangle signal, but not the rectangular signal. The body will consider A positive red blood cells as enemies and attack them. This reaction can be fatal.

This problem has existed since blood transfusions were first scientifically achieved, and scientists have been looking for a solution for just as long. It turns out the solution was hiding right under our noses; inside our stomachs, to be specific!

The findings

Inside the human gut are thousands of microscopic bacteria which we use to digest food and convert it into energy. As it turns out, these bacteria are very good at safely interacting with the human body in helpful ways.

The researchers removed these bacteria through human faeces and found they could be used in exactly the way they were hoping. “Why would they be looking in our stomachs for this solution?” you might ask.

 The Withers group were on a hunt for a special kind of protein called an enzyme. Enzymes are produced by the body with a very specific task, and that task varies based on what the body wants it to do.

 Since our gut has the ability to process blood and turn it into energy, Withers and his team decided to see if these enzymes could be harnessed for their research.  As it turns out, they were completely correct.

An enzyme interacting with a specific molecule (known as the substrate) and cutting it into two different products. Modified from Wikipedia Commons.

The group screened more than 20,000 samples to find two enzymes that were particularly good at cutting the signal on A-type blood leaving us with O-type blood. These were removed from the body and tested on real red blood cells.  

The researchers discovered that the enzymes could efficiently cut the specific part of the A-type blood, essentially leaving us with type O red blood cells.

 These two types of enzymes were 30 times more efficient than previous methods, which means we only need a tiny amount of these enzymes to convert A, B, and AB types of red blood cells to O type red blood cells.

Impacts

In January 2020, the American Red Cross announced that it has a ‘critical’ shortage of type O blood. In the United States and Canada alone, 4.5 million patients need blood transfusions every year.[2] 

This high demand means that oftentimes, the supply cannot meet the demand.

 With this new discovery, incompatible blood types can be made compatible. This would increase the supply of compatible blood, which means more people can be helped.

While the process has been completed in the lab, it has yet to be scaled up to convert massive amounts of blood at a time.  This may take some time to accomplish. 

However, countless people will be helped and countless lives will be saved. And if one thing is for certain, it’s that blood donations will forever be easier.

References
  1. Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Steven, J. H., Kizhakkedathu, J. N., Withers, S. G.; An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nature Microbiology. 2019, 1475-1485.
  2. Community Blood Bank of Northwest Pennsylvania and Western New York. 56 facts about blood. https://fourhearts.org/facts/ (accessed March 22, 2020)

– Griffin Bare, Eric Ding, Chantell Jansz

Leave a comment

Posted in Biological Chemistry, Chemistry News, Popular Science

Tagged , , , , ,

Sugars – The Key to Talking to Our Cells

Posted on April 9, 2020 by | Leave a comment

We are one step closer to achieving communication with those 37.2 trillion tiny cells making up our bodies. Just last year, researchers at the University of British Columbia, led by Dr. Stephen Withers, found a way to modify the sugars essential to this communication by using chemicals found in bacteria. The same bacteria living in our gut!

WHAT EXACTLY ARE SUGARS?

No ambiguity here! Chemists work with sugars based off molecules in this sugar cube. Credits: The Verge

To be specific, the sugars Withers’ team studied were simple sugars; hexagonal-shaped molecules, often joined to other molecules known as “acceptors”. The problem chemists face is like the average love life. 

Similar to starting a relationship with someone, joining acceptors to sugars is also quite difficult. Luckily for sugars, Mother Nature has come up with some solutions: enzymes, which are helper molecules that speed up the pairing or unlinking of two molecules.

A SOLUTION UNDER OUR NOSES…

Instead of struggling to find ways of joining sugars and acceptors, Withers’ team thought: Why not hijack Mother Nature and use these enzymes? To make their idea a reality, they extracted sugar-specific enzymes from E. Coli, a type of bacteria that lives inside the human gut.

These bacteria manufactured 175 sugar-specific enzymes, and from these they chose eight enzymes that were compatible with the sugars and acceptors they were interested in.

It seemed like Withers’ team now had everything needed to join the desired acceptors to the sugars; however, there was still a problem. The sugar-specific enzymes they got from E. Coli did the exact opposite of what they wanted; instead of forming sugar-acceptor linkages, they specialized in breaking them.

Enzymes that break sugar-acceptor linkages are analogous to using a screwdriver to loosen a screw, while enzymes that form sugar-acceptor linkages are like tightening a screw.

A small modification changes the function of the enzyme. Credits: Blog post authors

To solve this problem, they reverse-engineered the enzymes specialized in breaking linkages into those that form linkages, by changing a small part of the enzymes’ structure, similar to changing the tips on a screwdriver. As a result, Withers’ team now had eight enzymes specialized in forming different sugar-acceptor linkages. 

MORE THAN JUST A BOND…

Now being able to freely and efficiently modify sugars, there is a big potential for researchers to join in on the conversations with our cells. Why is this important? Often, there is miscommunication within our cells which can lead to serious trouble. 

One example is cancer; which is partly caused by cancer cells using abnormal sugar molecules as a form of miscommunication, to avoid being cleared up by immune cells. One potential treatment is a sugar-based vaccine, which allows our immune cells to more efficiently target tumor cells.

The challenge of creating a sugar-based vaccine isn’t just relevant to cancer, but other diseases as well which also occur  as a result of miscommunication. With Withers’ research, designing these sugar-based drugs won’t be as difficult thanks to their novel way of bonding sugars to other molecules. This research brings us one step closer to talking to our cells, helping with the battle against diseases.

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, Pricia Ouyang, Tom Hou, Aron Engelhard (CO-10)

Leave a comment

Posted in Biological Chemistry, Chemistry News, Organic Chemistry, Uncategorized

Tagged , ,

H2hox and Gallium: A Dynamic Duo in Medical Imaging

Posted on April 5, 2020 by | Leave a comment

Not every molecule gets to find their best “partner” in life. Luckily in 2019, Dr. Chris Orvig and his team at the University of British Columbia constructed a partner molecule for Gallium to work with in medical imaging. They also determined that their creation has superior stability and binding ability compared to similar molecules currently being used.

THE NEW MOLECULE IN TOWN

The partner molecule is a chelating ligand known as H2hox. Let’s break down its name piece-by-piece to get a better understanding of what it does.

A ligand is a molecule that binds onto a metal ion such as iron (Fe3+) or copper (Cu2+). In the case of H2hox, the metal ion is Gallium (Ga3+ ).

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.

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

THE DUO GETS TO WORK

H2hox is used in a form of medical imaging known as positron-emission tomography (PET). PET imaging is used to diagnose health issues related to the processes occurring inside our cells, such as cancer.

The main function of H2hox in PET imaging is to bind to radioactive Gallium ions, which aids in producing an image of a desired area or tissue inside the body.

To test how well H2hox worked together with its partner, Gallium, the researchers conducted a PET scan in mice. The group witnessed high stability of the dynamic duo within mice, and they observed that it was rapidly excreted from the mice, which is important for a decrease in side effects.

Furthermore, the ligand has a strong affinity to Gallium, such that only low amounts of ligand are needed to significantly bind to Gallium ions in just five minutes! As a result of the molecule’s advanced properties, H2hox surpasses any ligand currently used as a Gallium’s partner.

ALL IT TAKES IS 1 STEP

In the lab, H2hox is synthesized (made) in only one reaction and is easy to purify, unlike similar ligands which are synthesized over multiple labor- and resource- intensive steps. As a bonus, the chemicals used to make it are inexpensive and readily available.

To put this into perspective, it’s like baking a box cake versus baking a cake from scratch. The former is quite easy to do, while the latter is a lot harder and is more labour-intensive. Ease of manufacturing is a key feature because it determines the commercial success of the product.

THE FUTURE IS PROMISING

The combination of unprecedented properties and easy synthesis makes H2hox a launching-off point for the development of even better chelating ligands to improve the future of PET imaging. With H2hox being such an advantageous molecule for Gallium PET imaging, we cannot wait to see what else this dynamic duo has to offer the world.

Literature cited:

  1. Wang, X.; Jaraquemada-Pelaez, M. d. G.; Cao, Y.; Pan, J.; Lin, K.-S.; Patrick, B.O., Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for 68Ga Radiopharmaceuticals. J. Am. Chem. Soc. 2019, 58, 2275-2285

 

-Group 6 (Mark, Akash, Athena, Charles)

Leave a comment

Posted in Biological Chemistry, Chemistry News, Inorganic Chemistry, Uncategorized

Tagged , , , , , , , ,

Sugars – The Key to Talking to our Cells

Posted on March 30, 2020 by | Leave a comment

We are one step closer to achieving communication with those 37.2 trillion tiny cells making up our bodies. Our cells communicate using sugars, and different modifications to these sugars can change the way our cells communicate with each other. Just last year, researchers at the University of British Columbia, led by Dr. Stephen Withers, did exactly this! They designed a unique way to tinker with sugars’ chemical structures by using chemicals found in bacteria. The same bacteria living in our gut.

what exactly are sugars?

No ambiguity here! Chemists work with sugars based off molecules in this sugar cube. Credits: The Verge

To be specific, the type of sugars Wither’s team studied were simple sugars; hexagonal-shaped molecules, often joined to other molecules known as “acceptors”. The problem chemists face is like the average love life. Similar to starting a relationship with someone, joining acceptors to sugars is also quite difficult. Luckily for sugars, Mother Nature has come up with some solutions: enzymes, which are helper molecules that speed up the pairing or unlinking of two molecules. 

A SOLUTION UNDER OUR NOSES…

Instead of struggling to find ways of joining sugars and acceptors, Wither’s team thought: Why not hijack Mother Nature and use these enzymes? To make their idea a reality, they extracted sugar-specific enzymes from E. Coli, a type of bacteria that lives inside the human gut. These bacteria manufactured 175 sugar-specific enzymes, and from these they chose eight enzymes that were compatible with the sugars and acceptors they were interested in.

It seemed like Wither’s team now had everything needed to join the desired acceptors to the sugars; however, there was still a problem. 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. Enzymes that break sugar-acceptor linkages are analogous to using a screwdriver to loosen a screw, while enzymes that form sugar-acceptor linkages are like tightening a screw.

A small modification changes the function of the enzyme. Credits: Blog post authors

To solve this problem, they reverse-engineered the enzymes specialized in breaking linkages into those that form linkages, by changing a small part of the enzymes’ structure, similar to changing the tips on a screwdriver. As a result, Wither’s team now had eight enzymes specialized in forming different sugar-acceptor linkages. 

More than just a bond…

Now being able to freely and efficiently modify sugars, there is a big potential for researchers to join in on the conversations with our cells. Why is this important? Often, there is miscommunication within our cells which can lead to serious trouble. 

One example is cancer; which is partly caused by cancer cells using abnormal sugar molecules as a form of miscommunication, to avoid being cleared up by immune cells. One potential treatment is a sugar-based vaccine, which tells our immune cells to ignore this miscommunication and target tumor cells.

The challenge of designing a sugar-based vaccine isn’t just relevant to cancer, but other diseases as well which occur also as a result of miscommunication. With Wither’s research, designing these sugar-based drugs won’t be as difficult thanks to their novel way of bonding sugars to other molecules. This research brings us one step closer to talking to our cells, helping with the battle against diseases.

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, Pricia Ouyang, Tom Hou, Aron Engelhard (CO-10)

Leave a comment

Posted in Biological Chemistry, Chemistry News, Organic Chemistry, Uncategorized

Tagged ,

The Next Step in Antibiotics

Posted on March 30, 2020 by | Leave a comment

Did you know that not all types of bacteria in this world are harmful to humans? Some bacteria can be beneficial such as those used for the production of cheese and yogurt. Furthermore, these tiny creatures could even potentially be used to manufacture antibiotics for human use.

Antibiotics are used to cure bacterial infections by killing bacteria. For example, penicillin saved thousands of people in the 19th century.

Bacteria

As Amazing as they Sound, Antibiotics are not a Permanent Solution

The over-usage of antibiotics results in bacteria that can build resistance and cause the medication to be ineffective. The World Health Organization announced: “A serious threat is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone” on the development of drug-resistant bacteria.

Once a type of bacteria develops a resistance to a specific antibiotic, other antibiotics must be used to treat the infection. For example, nitroimidazole is a drug found in antibiotics such as azomycin. Due to its low resistance by bacteria, it has been used extensively to treat bacteria that have developed resistance to certain antibiotics.

Nitroimidazole

Research Looking into Nitroimidazole

Dr. Jason Hedges and Dr. Katherine Ryan of the University of British Columbia took a look into finding new ways to synthesize nitroimidazole. Their recent publication in 2019 showed how they were able to convert an amino acid (a building block of proteins) into azomycin. 

The researchers used bioinformatics, a data analysis tool, to find all previous work that has been done on this topic. Bioinformatic searches are performed on databases such as NCBI.

They found that back in 1953, azomycin was extracted from a strain of bacteria called Streptomyces eurocidicus. Furthermore, they found a specific gene in a separate strain of yeast called Streptomyces cattleya, which had similarities to S. eurocidicus. 

The two researchers aimed to find new ways to synthesize nitroimidazole, and proposed to synthesize nitroimidazole from L-arginine. Once a pathway had been developed, their end goal was to synthesize and extract azomycin in S. cattleya.

Hedges and Ryan were able to develop a multi-step pathway for the conversion of L-arginine to nitroimidazole through experimentation. However, they were unable to detect azomycin in S. cattleya. They noted that the gene of interest was unable to synthesize azomycin, and a separate drug may have synthesized in its place.

Synthesize of nitroimidazole from L-Arginine

A Bright Future

The significance of this research transcends the synthesis of azomycin. Although they failed to detect azomycin in S. cattleya, their work provides a stepping stone for further research to be conducted. This study provides insight on new biosynthetic pathways which is important to those currently in the field of life sciences and pharmacology. Furthermore, this study expands people’s knowledge of bacteria engineering and the biosynthetic pathway of other antibiotics. It also provides information about future antibiotic observations.

Future researchers could test their synthetic pathway on other bacteria such as E. coli to determine if azomycin could be synthesized.

Reference:

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.

-Adrian Emata/Jackson Kuan/Xinyu Gu/Yicheng Zhu

 

 

 

Leave a comment

Posted in Biological Chemistry, Chemistry News, Organic Chemistry

The Key to Treating Pneumonia can be Found in Soil?

Posted on March 27, 2020 by | Leave a comment

Can it really be that simple? Can the answer really be in the ground beneath our feet?

Source: Soil Science Society of America

Discovery of a gene cluster commonly found in soil-dwelling bacteria may be the key to treating anaerobic bacterial infections such as appendicitis and pneumonia. Researchers Jason B. Hedges and Prof. Dr. Katherine S. Ryan from the University of British Columbia have isolated the antibiotic compound azomycin from a biosynthetic gene cluster found in the bacterium Streptomyces cattleya.

With this information they believe it can lead to engineering bacteria to produce a new line of antibiotics.

What is a gene cluster?

The term gene cluster is moreso semantics to describe a group of genes that share a common phenomenon.

Originally, azomycin was isolated from a similar bacterium Streptomyces eurocidicus back in 1953 and became the blueprint to synthetic nitroimidazoles. 

“Nitroimidazoles are one of the most effective ways to treat anaerobic bacterial infections”,[1] Hedges writes in his 2019 study. The most commonly used nitroimidazole, metronidazole, is an antibiotic used to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis.[2] It is also on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.[3]

Figure 1: Molecular Structure of Nitroimidazole. Source: Sigma Aldrich

Despite its use in antibiotics for over 60 years, the incidence of nitroimidazole resistance in anaerobes remains low, making it an essential component of the antibiotic arsenal. [1,4]

Since the isolation of azomycin back in 1953, synthesis of nitroimidazoles were limited to synthetic routes, most commonly involving reactions of an imidazole with nitric acid and sulfuric acid. 

Using bioinformatics, however, in 2019 Hedges and Ryan were able identify a biosynthetic gene cluster in the same bacterium that makes penicillin,[5] Streptomyces cattleya. They were able to find that this gene cluster containing azomycin is widely distributed among soil-dwelling actinobacteria and proteobacteria.

Because of this they theorize that azomycin and other nitroimidazoles may be important factors in ecology.

What are bioinformatics?

Bioinformatics is the science of collecting and analyzing complex biological data such as genetic codes. As an interdisciplinary field of science, bioinformatics combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret the biological data

In addition to the isolation of azomycin in a gene cluster, Hedges and Ryan were able to perform in vitro analysis in order to understand the enzymatic steps that take the primary protein L-arginine to become azomycin. 

Source: Washington Post

Their work opens the door to biocatalytic methods to synthesize azomycin and other nitroimidazoles. They believe this discovery can “lead to the possibility of engineering bacteria to produce nitroaromatic compounds”.[1]

In other words, this may lead to stronger antibiotics immune to drug resistance.

References

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.

The American Society of Health-System Pharmacists. Archived from the original on 6 September 2015. Retrieved 31 July 2015.

World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization

David I. Edwards, Nitroimidazole drugs-action and resistance mechanisms I. Mechanism of action, Journal of Antimicrobial Chemotherapy, Volume 31, Issue 1, January 1993, Pages 9–20, https://doi.org/10.1093/jac/31.1.9

Kahan, JS; Kahan, FM; Goegelman, R; Currie, SA; Jackson, M; Stapley, EO; Miller, TW; Miller, AK; Hendlin, D; Mochales, S; Hernandez, S; Woodruff, HB; Birnbaum, J (Jan 1979). “Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties”. The Journal of Antibiotics. 32 (1): 1–12

-Adrian Emata

Leave a comment

Posted in Analytical Chemistry, Biological Chemistry, Chemistry News, Organic Chemistry, Popular Science

Tagged , ,

No Medicine to Cure

Posted on March 23, 2020 by | Leave a comment

Can you imagine the world without medicine?

Nowadays, more and more bacteria begin to show resistance against antibiotics. Azomycin, a type of antibiotics used to treat multi-drug resistance is found to be used more and more frequently. What if bacteria start to grow resistance against Azomycin? However, it is actually nailed fact, the only question is when. In order to solve this problem, in 2019, Dr. Jason Hedges and Dr. Katherine Ryan of the University of British Columbia engaged in finding a new way to synthesize the nitroimidazole, the main component of azomycin.

source:https://www.reactgroup.org/toolbox/understand/how-did-we-end-up-here/few-antibiotics-under-development/

The study of antibiotics can be traced back to the 19th century. For these two centuries, antibiotics saved countless lives from all kinds of diseases. However, antibiotics can not kill all the bacteria. Every time when one bacteria survived from the massacre of the antibiotic, they grow the resistance against the antibiotic. Then it split, split and split. Finally, the survived bacteria become countless bacteria that can not be defeated by the antibiotic again. Thus, more and more bacteria begin to survive from the war with antibiotics, and more and more antibiotics become useless. Herein, the race between the evolving of antibiotics and evolving of bacteria begins. 

So, let’s take a look at what did Dr. Jason Hedges and Dr. Katherine Ryan do and what did they find.

By doing a lot of research, Dr. Jason Hedges and Dr. Katherine Ryan found that the development of nitroimidazole can be dated back to 1953 when azomycin was first found. And they noticed that when strain Streptomyces eurocidicus was produced, L-arginine is converted to azomycin. Therefore, they came up with a plan to synthesis nitroimidazoles by linking L-arginine to azomycin via in vitro reconstitution. 

In vitro reconstitution process of nitroimidazole. Source: Hedges and Ryan, 2019

Through the experiment, Dr. Jason Hedges and Dr. Katherine Ryan successfully synthesized nitroimidazole via in vitro reconstitution. But unfortunately, no azomycin was produced via Streptomyces cattleya. 

Although the experiment is failed to synthesis azomycin through Streptomyces cattleya, it still provides a lot of valuable information for further researchers. It points a direction on the biocatalytic pathway of azomycin synthesis and set the stage for the discovery of new antibiotics.

Reference:

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.

 

Yicheng Zhu

 

 

 

 

 

Leave a comment

Posted in Biological Chemistry, Chemistry News, Organic Chemistry

Biosynthetic Pathway Found to Synthesize Anaerobic Antibiotics!

Posted on March 23, 2020 by | Leave a comment

Fig 1. Image of Azomycin. source

Scientists found the biosynthetic pathway to the Nitroimidazole Antibiotic Azomycin. A steppingstone towards the revolution of anaerobic bacterial infection treatments.

Scientists from the University of British Columbia found the biosynthetic pathway to the Nitroimidazole antibiotic Azomycin. The enzymatic mechanism from L-Arginine to Nitroimidazole has now been proved and present to the public. Their formal paper was published online on July 17th, 2019. Nitroimidazole is an essential component for the modern antibiotics, it is crucial to know its synthetic pathway for further pharmaceutical studies. The result of their study set the stage for further development of important anaerobic antibiotic Azomycin.

What is it? Why do we need to know about this?

Nitroimidazole is an essential antibiotic specifically to treat anaerobic bacterial infections. They are widely used to treat diseases such as Amoebiasis, Parasitic infections, skin infections, diarrhea and so on. The low redox potential of anaerobic bacteria cells allowed nitroimidazole to act as the electron sink and form the radical species. The resultant radical species would induce the bacteria cells’ death by damaging their DNA. Antibiotic is the most powerful “weapon” to fight against bacterial infections. However, according to the World Health Organization, there are more than 700000 people die every year due to antibiotic resistance. Despite the several decade’s usages of Nitroimidazole antibiotics, the drug resistance of it still remains low relatively. Thus, Nitroimidazole antibiotics are increasingly used to treat multi-drug resistant bacteria as well.

 

Previous research established that L-Arginine is converted to azomycin by 2-aminioimidazole. They determined that the intermediate of the reaction is 4-hydroxy-2-ketoarginine (2). Furthermore, they also observed the accumulation of pyruvate(3) side products and 2-aminoimidazole(5) from the intermediate(2). However, the actual enzymatic synthetic pathway has not been determined detailly yet. Jason and Katherine in the research group determined that PLP-dependent enzymes, RohP,RohR,RohQ and RohS plays esstential role in the catalytic pathway of the reaction. Researchers examined the in vitro activity of RohP, RohR, RohQ and RohS. They put in these enzymes separately and stepwise to different reactants. For example, in order to test whether RohR could catalyze a retro-aldol cleavage of 2 into 3 and guanidinoacetaldehyde (4), they added purified RohR instead of RohP. Then according to activity analysis and also the mass spectrum, the result shows that RohP yields a bigger portion of 2.

Fig 2. Reaction scheme from L-Arginine to Nitroimidazole. Source

Antibiotics are the most powerful “weapon” to kill bacteria in modern pharmaceutical studies. As early as in the 20th century, the observation of penicillin saved millions of people injured in the World War. Yet, the enormous benefits of antibiotics cause the consequences of drug-resistance. Azomycin, consider as a low-resistance antibiotic, it is crucial to understand its enzymatic reaction mechanism. Reaction mechanism allows scientist to have a more detail interpretation of the synthesis. It is crucial to find the catalytic cycle of the reaction, in order to allow scientists to develop and derive further study.

The study done by Jason and Katherine at the University of British Columbia provides the public with a steppingstone in future nitroimidazole anti-biotics study. Their study expanded people’s knowledge of the biosynthetic pathway to nitro-compounds. It also makes bacteria engineering to produce nitroaromatic compounds possible. This study will open the new door in enzymatic synthesis and biochemistry synthesis.

Cited article:

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.

Leave a comment

Posted in Analytical Chemistry, Biological Chemistry, Chemistry News, Organic Chemistry, Popular Science, Uncategorized

Tagged , ,

Life Saving Improvements to Blood Transfusions

Posted on March 23, 2020 by | Leave a comment

Previously thought impossible, researchers have found a way to create O type blood from other blood types. Since O is a universal donor, these other blood types can now be used as universal donors, potentially saving countless lives.

A team of biochemists from the University of British Columbia, lead by doctor Stephen Withers, have turned A positive and A negative type blood into the universal O type blood. These findings were published in June of 2019 in the journal “Nature Microbiology.”[1]

Before these findings, the 8 major blood types were not all compatible with each other. This meant that if a blood transfusion were needed for a patient, a specific type of blood maybe be needed, with no other type working.

A chart of what blood types can donate or receive other blood types.[2]

This problem has existed since blood transfusions were first scientifically achieved, and scientists have been looking for a solution for just as long. It turns out the solution was hiding right under our noses; inside our stomachs, to be specific!

Inside the human gut are thousands of microscopic bacteria which we use to digest food and convert it into energy. As it turns out, these bacteria are very good at safely interacting with the human body in helpful ways. The researchers extracted these microorganisms through human feces and found they could be used in exactly the way they were hoping.

“Why would they be looking in our stomachs for this solution?” you might ask. The Withers group were on a hunt for a special kind of protein called an enzyme. Enzymes are produced by the body with a very specific task, and that task varies based on what the body wants in to do. In the below picture, notice how the enzyme matches perfectly the substrate. This is because enzymes are made for specific purposes, and only match specific molecules in the body. Since our gut has the ability to process blood and turn it into energy, Withers and his team decided to see if these enzymes could be harnessed for their research.  As it turns out, they were completely correct.

An enzyme interacting with a specific molecule (known as the substrate) in the body.[3]

Future Impacts

 In the United States and Canada alone, 4.5 million patients need blood transfusions every year.[4] This high demand means that often times, the supply cannot meet the demand. With this new discovery, more blood types are compatible, which means more people can be helped.

While the process has been completed in the lab, it has yet to be scaled up to convert massive amounts of blood at a time.  This may take some time to accomplish. However, it is impossible to quantify exactly how many people this new method will help, or even how many lives it will save. One thing is for certain,  is that the world of blood donations will forever feel the impact of these findings. 

 References:

  1. Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Steven, J. H., Kizhakkedathu, J. N., Withers, S. G.; An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nature Microbiology. 2019, 1475-1485.
  2. Canadian Blood Services. Do You Know Your Blood Type? https://blood.ca/en/blood/donating-blood/whats-my-blood-type (accessed March 21, 2020)
  3. Western Oregon University: Chemistry. CH450 and CH451: Biochemistry – Defining Life at the Molecular Level. Chapter 6: Enzyme Principles and Biotechnological Applications. https://wou.edu/chemistry/courses/online-chemistry-textbooks/ch450-and-ch451-biochemistry-defining-life-at-the-molecular-level/chapter-7-enzyme-kinetics/ (accessed Mar 21, 2020)
  4. Community Blood Bank of Northwest Pennsylvania and Western New York. 56 facts about blood. https://fourhearts.org/facts/ (accessed March 22, 2020)

Leave a comment

Posted in Biological Chemistry, Chemistry News, Popular Science

Tagged ,

Making Different Sugars with Enzyme (Pac-Man) In Our Body

Posted on March 23, 2020 by | Leave a comment

Although eating too much sugar can lead to health complications, a normal intake of sugar has its benefits. This is because sugars take part not only in many cellular activities as an energy source but also in cell-cell communication as a communicator. In 2019, a research team led by Dr. Stephen Withers at the University of British Columbia made different sugars by using enzymes (Pac-Man-like molecules) in bacteria. This finding enables the building of many sugars that are commonly hard to find in nature.

What are sugars?

All sugars are made of hexagonal building blocks as shown in red in Figure 1. Two common building blocks are glucose and fructose. To make different sugars with only two common building blocks, we can vary the number and arrangement of the building blocks. For example, cellulose has three long threads that are arranged almost parallel to each other. In contrast, starch has one long thread that adopts a helical structure.

Now we know that different sugars can be made by varying the kinds of building blocks, the numbers of building blocks and the arrangements of building blocks. What we haven’t talked about is how the building blocks are linked. There are two issues with linking the building blocks. First, building blocks are much smaller than our cells. Getting two building blocks together is as hard as fishing a needle from the Pacific Ocean. Besides, getting two building blocks together takes time because they prefer to be alone. How can our mother nature solve these problems to keep us alive?

Figure 1. Sugars are built differently. Some sugars are longer and more complex than others. Source: riasparklebiochemistry

Here comes the rescue…Pac-Man in the cells!

The illustrations of enzymes are like Pac-Man. However, different from Pac-Man that eats any “food” in different shapes, enzymes recognize different substrates and those substrates only! Because of this substrate-enzyme specificity, linking two building blocks together is much easier. As shown in Figure 2, the enzyme will attract two specific building blocks, making them closer to each other and eventually join.

Figure 2. Different enzymes recognize different substrates. Source: Wikipedia

Besides, enzymes can speed up the “hugging” process between the substrates (building blocks), making the formation of a long sugar favorable.

Figure 3. Enzymes speed up reactions. Source: pinimg.com

Manipulation of enzymes to build different sugars for cell-cell communication

Knowing that enzymes have many advantages, Dr. Wither and his team looked for enzymes that speed up the linkage of sugar building blocks in E. Coli, bacteria that live inside our digestive tracts. They chose eight enzymes out of the 175 sugar-specific enzymes in E. Coli. These eight enzymes were the most specific to the sugar building blocks they were interested in. However, after further investigation, the researchers found that the enzymes helped speed up the breakage of the linkage(s) between sugar building blocks instead of the formation of the linkage(s).

Figure 4. Some enzymes speed up the breakage of linkages while others speed up the formation of linkages.
Source: Canstock.com

To solve this problem, the researchers reverse-engineered these enzymes from speeding up breakage to speeding up linkage by changing parts of the enzymes. Now different sugars can be made! As mentioned above, cell-cell communication relies on sugars. This is because two cells adhere via the interaction between extracellular sugars and specific cell-surface receptors. Once these cells adhered to each other, they can talk to each other about their internal cellular condition/environment and trigger a corresponding response. This has great implications in triggering an immune response to a viral attack. By engineering more sugars on the surface of the cells, cells in our immune system can more quickly talk to each other and fight off infection.

 

Journal 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.

-Pricia Ouyang

Leave a comment

Posted in Biological Chemistry, Chemistry News, Organic Chemistry, Popular Science, Uncategorized

Tagged , , , ,