Placeholder Image

字幕列表 影片播放

  • Translator: Ivana Korom Reviewer: Krystian Aparta

  • Growing up in central Wisconsin, I spent a lot of time outside.

  • In the spring, I'd smell the heady fragrance of lilacs.

  • In the summer, I loved the electric glow of fireflies

  • as they would zip around on muggy nights.

  • In the fall, the bogs were brimming with the bright red of cranberries.

  • Even winter had its charms,

  • with the Christmassy bouquet emanating from pine trees.

  • For me, nature has always been a source of wonder and inspiration.

  • As I went on to graduate school in chemistry, and in later years,

  • I came to better understand the natural world in molecular detail.

  • All the things that I just mentioned,

  • from the scents of lilacs and pines

  • to the bright red of cranberries and the glow of fireflies,

  • have at least one thing in common:

  • they're manufactured by enzymes.

  • As I said, I grew up in Wisconsin, so of course, I like cheese

  • and the Green Bay Packers.

  • But let's talk about cheese for a minute.

  • For at least the last 7,000 years,

  • humans have extracted a mixture of enzymes

  • from the stomachs of cows and sheep and goats

  • and added it to milk.

  • This causes the milk to curdle -- it's part of the cheese-making process.

  • The key enzyme in this mixture is called chymosin.

  • I want to show you how that works.

  • Right here, I've got two tubes,

  • and I'm going to add chymosin to one of these.

  • Just a second here.

  • Now my son Anthony, who is eight years old,

  • was very interested in helping me figure out a demo for the TED Talk,

  • and so we were in the kitchen, we were slicing up pineapples,

  • extracting enzymes from red potatoes

  • and doing all kinds of demos in the kitchen.

  • And in the end, though,

  • we thought the chymosin demo was pretty cool.

  • And so what's happening here

  • is the chymosin is swimming around in the milk,

  • and it's binding to a protein there called casein.

  • What it does then is it clips the casein --

  • it's like a molecular scissors.

  • It's that clipping action that causes the milk to curdle.

  • So here we are in the kitchen, working on this.

  • OK.

  • So let me give this a quick zip.

  • And then we'll set these to the side and let these simmer for a minute.

  • OK.

  • If DNA is the blueprint of life,

  • enzymes are the laborers that carry out its instructions.

  • An enzyme is a protein that's a catalyst,

  • it speeds up or accelerates a chemical reaction,

  • just as the chymosin over here is accelerating the curdling of the milk.

  • But it's not just about cheese.

  • While enzymes do play an important role in the foods that we eat,

  • they also are involved in everything from the health of an infant

  • to attacking the biggest environmental challenges

  • we have today.

  • The basic building blocks of enzymes are called amino acids.

  • There are 20 common amino acids,

  • and we typically designate them with single-letter abbreviations,

  • so it's really an alphabet of amino acids.

  • In an enzyme, these amino acids are strung together,

  • like pearls on a necklace.

  • And it's really the identity of the amino acids,

  • which letters are in that necklace,

  • and in what order they are, what they spell out,

  • that gives an enzyme its unique properties and differentiates it from other enzymes.

  • Now, this string of amino acids,

  • this necklace,

  • folds up into a higher-order structure.

  • And if you were to zoom in at the molecular level

  • and take a look at chymosin, which is the enzyme working over here,

  • you would see it looks like this.

  • It's all these strands and loops and helices and twists and turns,

  • and it has to be in just this conformation to work properly.

  • Nowadays, we can make enzymes in microbes,

  • and that can be like a bacteria or a yeast, for example.

  • And the way we do this is we get a piece of DNA

  • that codes for an enzyme that we're interested in,

  • we insert that into the microbe,

  • and we let the microbe use its own machinery, its own wherewithal,

  • to produce that enzyme for us.

  • So if you wanted chymosin, you wouldn't need a calf, nowadays --

  • you could get this from a microbe.

  • And what's even cooler, I think,

  • is we can now dial in completely custom DNA sequences

  • to make whatever enzymes we want,

  • stuff that's not out there in nature.

  • And, to me, what's really the fun part

  • is trying to design an enzyme for a new application,

  • arranging the atoms just so.

  • The act of taking an enzyme from nature and playing with those amino acids,

  • tinkering with those letters,

  • putting some letters in, taking some letters out,

  • maybe rearranging them a little bit,

  • is a little bit like finding a book

  • and editing a few chapters or changing the ending.

  • In 2018, the Nobel prize in chemistry

  • was given for the development of this approach,

  • which is known as directed evolution.

  • Nowadays, we can harness the powers of directed evolution

  • to design enzymes for custom purposes,

  • and one of these is designing enzymes for doing applications in new areas,

  • like laundry.

  • So just as enzymes in your body

  • can help you to break down the food that you eat,

  • enzymes in your laundry detergent

  • can help you to break down the stains on your clothes.

  • It turns out that about 90 percent of the energy

  • that goes into doing the wash

  • is from water heating.

  • And that's for good reason --

  • the warmer water helps to get your clothes clean.

  • But what if you were able to do the wash in cold water instead?

  • You certainly would save some money,

  • and in addition to that,

  • according to some calculations done by Procter and Gamble,

  • if all households in the US were to do the laundry in cold water,

  • we would save the emissions of 32 metric tons of CO2 each year.

  • That's a lot,

  • that's about the equivalent

  • of the carbon dioxide emitted by 6.3 million cars.

  • So, how would we go about designing an enzyme

  • to realize these changes?

  • Enzymes didn't evolve to clean dirty laundry,

  • much less in cold water.

  • But we can go to nature, and we can find a starting point.

  • We can find an enzyme that has some starting activity,

  • some clay that we can work with.

  • So this is an example of such an enzyme, right here on the screen.

  • And we can start playing with those amino acids, as I said,

  • putting some letters in, taking some letters out,

  • rearranging those.

  • And in doing so, we can generate thousands of enzymes.

  • And we can take those enzymes,

  • and we can test them in little plates like this.

  • So this plate that I'm holding in my hands

  • contains 96 wells,

  • and in each well is a piece of fabric with a stain on it.

  • And we can measure how well each of these enzymes

  • are able to remove the stains from the pieces of fabric,

  • and in that way see how well it's working.

  • And we can do this using robotics,

  • like you'll see in just a second on the screen.

  • OK, so we do this, and it turns out

  • that some of the enzymes are sort of in the ballpark

  • of the starting enzyme.

  • That's nothing to write home about.

  • Some are worse, so we get rid of those.

  • And then some are better.

  • Those improved ones become our version 1.0s.

  • Those are the enzymes that we want to carry forward,

  • and we can repeat this cycle again and again.

  • And it's the repetition of this cycle that lets us come up with a new enzyme,

  • something that can do what we want.

  • And after several cycles of this,

  • we did come up with something new.

  • So you can go to the supermarket today, and you can buy a laundry detergent

  • that lets you do the wash in cold water because of enzymes like this here.

  • And I want to show you how this one works too.

  • So I've got two more tubes here,

  • and these are both milk again.

  • And let me show you,

  • I've got one that I'm going to add this enzyme to

  • and one that I'm going to add some water to.

  • And that's the control,

  • so nothing should happen in that tube.

  • You might find it curious that I'm doing this with milk.

  • But the reason that I'm doing this

  • is because milk is just loaded with proteins,

  • and it's very easy to see this enzyme working in a protein solution,

  • because it's a master protein chopper,

  • that's its job.

  • So let me get this in here.

  • And you know, as I said, it's a master protein chopper

  • and what you can do is you can extrapolate what it's doing in this milk

  • to what it would be doing in your laundry.

  • So this is kind of a way to visualize what would be happening.

  • OK, so those both went in.

  • And I'm going to give this a quick zip as well.

  • OK, so we'll let these sit over here with the chymosin sample,

  • so I'm going to come back to those toward the end.

  • Well, what's on the horizon for enzyme design?

  • Certainly, it will get it faster --

  • there are now approaches for evolving enzymes

  • that allow researchers to go through far more samples

  • than I just showed you.

  • And in addition to tinkering with natural enzymes,

  • like we've been talking about,

  • some scientists are now trying to design enzymes from scratch,

  • using machine learning, an approach from artificial intelligence,

  • to inform their enzyme designs.

  • Still others are adding unnatural amino acids to the mix.

  • We talked about the 20 natural amino acids,

  • the common amino acids, before --

  • they're adding unnatural amino acids

  • to make enzymes with properties unlike those that could be found in nature.

  • That's a pretty neat area.

  • How will designed enzymes affect you in years to come?

  • Well, I want to focus on two areas:

  • human health and the environment.

  • Some pharmaceutical companies

  • now have teams that are dedicated to designing enzymes

  • to make drugs more efficiently and with fewer toxic catalysts.

  • For example, Januvia,

  • which is a medication to treat type 2 diabetes,

  • is made partially with enzymes.

  • The number of drugs made with enzymes is sure to grow in the future.

  • In another area,

  • there are certain disorders

  • in which a single enzyme in a person's body doesn't work properly.

  • An example of this is called phenylketonuria,

  • or PKU for short.

  • People with PKU are unable to properly metabolize or digest phenylalanine,

  • which is one of the 20 common amino acids that we've been talking about.

  • The consequence of ingesting phenylalanine for people with PKU

  • is that they are subject to permanent intellectual disabilities,

  • so it's a scary thing to have.

  • Now, those of you with kids --

  • do you guys have kids, here, which ones have kids?

  • A lot of you.

  • So may be familiar with PKUs,

  • because all infants in the US are required to be tested for PKU.

  • I remember when Anthony, my son, had his heel pricked to test for it.

  • The big challenge with this is: What do you eat?

  • Phenylalanine is in so many foods, it's incredibly hard to avoid.

  • Now, Anthony has a nut allergy, and I thought that was tough,

  • but PKU's on another level of toughness.

  • However, new enzymes may soon enable PKU patients

  • to eat whatever they want.

  • Recently, the FDA approved an enzyme designed to treat PKU.

  • This is big news for patients,

  • and it's actually very big news

  • for the field of enzyme-replacement therapy more generally,

  • because there are other targets out there where this would be a good approach.

  • So that was a little bit about health.

  • Now I'm going to move to the environment.

  • When I read about the Great Pacific Garbage Patch --

  • by the way, that's, like, this huge island of plastic,

  • somewhere between California and Hawaii --

  • and about microplastics pretty much everywhere,

  • it's upsetting.