Tag Archives: enzymes

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

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Life-saving improvements to blood transfusion

Posted on March 30, 2020 by | Leave a comment

An article published by Nature Microbiology in June 2019, 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.  

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.  When doctors are going to transfuse blood to patients, they need to match the type of blood to one that can safely match with the patient’s blood type. If they don’t, the body will not know how to handle the new type of blood. This can cause blood vessels to rupture, which 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!

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 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) in the body.[2]

The group screened more than 20,000 samples to find two enzymes that were particularly good at cleaving the A-type blood. These were extracted and tested on real red blood cells and found that the enzymes could efficiently cleave a 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.

Image depicting the difference between blood types A, O, and B. The image shows that removing the yellow square in A type blood, is the same as O type blood. Modified from [1].

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.[3] 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, 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, 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. 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)
  3. 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

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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)

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

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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

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

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