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Elizabeth Sattely: Plants are the ultimate chemists

They make a remarkable array of chemicals to survive the world around them. One engineer is using that knowledge to help people live better.

‘Bloom where you’re planted’ isn't just a catchy phrase in the plant kingdom, it’s a matter of survival. | Unsplash/Lesly Juarez

‘Bloom where you’re planted’ isn't just a catchy phrase in the plant kingdom, it’s a matter of survival. | Unsplash/Lesly Juarez

When things aren’t going well for humans and other ambulatory creatures, they simply move on to a new location, a new life.

For plants, it’s different, says chemical engineer Elizabeth Sattely, who studies the evolutionary adaptations plants make to survive.

Unable to migrate, plants must make do with the hand that’s dealt them. And sometimes that hand is not very good. The soils where they are rooted can lack nutrients or play host to pathogens. The air can be polluted or too arid.

This fact of life, however, has given rise to a remarkable breadth of evolutionary adaptations plants use to make the best of their surroundings. They produce powerful small molecules that help them get more nutrients from the soil or air. And, they partner with microbes that help them live.

Sattely hopes to better understand and, possibly, employ these adaptations for human benefit by making crops more robust to environmental challenges and by learning how the small molecules plants create impact human health. She says we might even turn plants into biofactories that produce medicines and other valuable chemicals.

Join host Russ Altman and Sattely for a deeper look at the remarkable world of plant biochemistry. You can listen to The Future of Everything on Sirius XM Insight Channel 121iTunesGoogle PlaySoundCloudSpotifyStitcher or via Stanford Engineering Magazine.

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Russ Altman: Today on The Future of Everything, the future of plant chemistry.

Now, forgive me, but plants are fantastic living organisms. They do photosynthesis, which is pretty much a miracle. It’s the ability to take the energy and photons of light, from the sun, photons, and transform carbon dioxide, which is basically a waste product, into glucose, that can fuel all the processes of life. We humans can’t do that, and so we rely on plants to take the energy of the sun and turn it into stuff basically that we can eat. And by the way, oxygen is a by-product of the photosynthesis, so guess where we get lots of our oxygen from as well.

So there you go, right there, photosynthesis is a highlight of life on earth. Plants are also, of course, a source of food for most of the food chain, not just humans. They also make very complex and interesting chemicals that are needed for their life processes. They’re also needed for combating fungi that they might be waging battle with, and other organisms that are dangerous or a threat to them. They create shade, ground cover, okay, you all know what plants are so I don’t wanna belabor this.

But plants are also stressed by the environment, by environmental conditions just like other organisms are stressed by global warming, pollution, changes in rain patterns, and changes in nutrient availability within soil. There is a vibrant research community looking at plants in two complimentary ways. How can we help them be more robust, grow well in difficult conditions, and make more of the good stuff, oxygen, glucose, nutrients, drugs? And how can we understand their amazing ability to make powerful molecules that we can harness for cancer, antifungals, and other medical and industrial purposes?

Dr. Elizabeth Sattely is a Professor of Chemical Engineering at Stanford University who studies plant chemistry. She is particularly focused on manufacturing and engineering molecules from plants, enhancing plant fitness, and looking for new ways to use the chemicals in wood as food, something that is not my first choice, but I’m open-minded.

Now Beth, some of your work is focused on helping crops grow in difficult soils. You had to engineer the plants to have some different capabilities from kind of what they had naturally, but the upside could be a much better food supply eventually, in areas that are traditionally tough to farm. So my question is, what is the basis for this new capability for growing plants, and how does the technology look for scaling?

Elizabeth Sattely: Yeah, so let me back up a second —

Russ Altman: Sure.

Elizabeth Sattely: — and just tell you a little bit about what I find really fascinating about plants. This is a whole kingdom of life, and there’s all different chemistries that have evolved across the plant kingdom to deal with these different environmental stresses. All the same things we have to deal with, plants have to deal with, and they do it exactly where they’re planted. They don’t have an option of moving or going somewhere else.

Russ Altman: Right.

Elizabeth Sattely: What we really find fascinating is how different chemistries have evolved in plants to help them do this. How does a small molecule that a plant makes allow it to get vitamins out of the soil that we just get through our diet?

Russ Altman: Right.

Elizabeth Sattely: With the crops we grow, when you think about the whole plant kingdom, we only grow a very small number of plants, and those plants are not necessarily, they haven’t evolved to deal with all the different types of environmental stresses that a plant might encounter. What’s really interesting to me is this idea that you might be able to take a mechanism that evolved in one corner of the plant kingdom, and move it into a crop that we grow for food and enable it to grow in a more efficient way without as many fertilizer inputs, and deal with environmental stresses better.

Russ Altman: That makes a lot of sense because not only do we only grow a subset of the plants as you say, but my understanding is, they’ve been highly evolved through husbandry and what not, I don’t know if it’s husbandry, but through farmer selection to be particularly good at growing in particular situations, and as those situations change, they might be even less prepared than a normal plant to adapt to changing environments.

Elizabeth Sattely: Exactly, we’ve bred plants for certain traits, and as we start to care about different things, for example, environmental impact of the agriculture that we do, we might change what types of traits we want in the crops that we grow.

Russ Altman: Tell me about this work that you did. It got some press recently. It was the first step in what could be a multi-step process for strengthening and making our plants more robust.

Elizabeth Sattely: Right, so I was really going back. I’m a chemist and I’m just really interested in the role of small molecules. How can organisms use small molecules to do the stuff they have to do?

Russ Altman: Yes.

Elizabeth Sattely: Plants are especially good at this. You pointed out at the beginning how plants take CO2 and they build virtually all the building blocks for life as we know it. All the molecules in your body were born in a plant through photosynthesis. I was really interested in this challenge plants have of the seed lands where it lands, the plant starts growing, and it needs to get all the nutrients it needs for life. Now, photosynthesis is super cool. You can take photons, CO2, and make things. But there’s actually a lot more required to make a whole organism.

Russ Altman: Right.

Elizabeth Sattely: One thing is iron, and that’s just one of many different micronutrients that all organisms need in order to carry out their life processes. Plants, just like us, require iron to drive enzyme catalysis to make all those different molecules. I was really interested to find that iron is actually the fourth most limiting nutrient for plant growth. Wherever the roots land, they’re kind of like inside out intestines you can think about it.

Russ Altman: Yep.

Elizabeth Sattely: They need to be able to get iron from the soil, and if there’s not iron nearby, or it’s not very available, that’s gonna be a limitation for growth. And so, what we’ve been able to find, we and others have learned, that plants produce small molecules, they exude them, or secrete them from their roots, and it helps them get iron.

Russ Altman: Into the soil.

Elizabeth Sattely: Into the soil that might be distal from where they are. So again, you know we think about plants, they need to grow where they’re planted, but they actually have a reach that’s further than that.

Russ Altman: Tell me about these secreted molecules. Did you actually give some of these secreted molecules to plant roots that didn’t have them previously to kind of increase their ability to grab iron?

Elizabeth Sattely: Really at this point, we’re just trying to figure out what kinds of things do plants do to deal with these types of environmental stresses.

Russ Altman: So we need to understand what their arsenal of tools is.

Elizabeth Sattely: Exactly, and like I said, different tools have evolved across the plant kingdom, so one large set of plants have evolved this ability to secrete molecules that actually can grab iron, change its chemical state, and make it easier and more bioavailable to take up by the roots.

Russ Altman: It’s almost like pre-processing the iron to make it easier to absorb.

Elizabeth Sattely: Right.

Russ Altman: And then all you have to do if you’re the plant, so to speak, is grow a root towards where that molecule has helped prepare the iron, and there the iron is, ready to go, whereas it wouldn’t have been ready to go if you hadn’t secreted that whatever it is.

Elizabeth Sattely: Yeah, and if I talk about kind of where this project started for me and for my lab, what we’ve been really interested in, is all the genome sequencing that’s been done in plants. If you sequence a new plant genome, what we quickly realize, after we get all those A’s, G’s, T’s and C’s lined up, is that plants can make a huge amount of different small molecules. In my lab, that’s just been fascinating for us. Why do plants make all these small molecules and what are we doing? So we kind of started from a standpoint of this interesting gene in a plant that we realized could make a small molecule, and then asked what was it doing? And this, one after another, led us to this small molecule that’s important for acquiring iron.

Russ Altman: So that is amazing, because I’m sure you then look at these genomes, which are very complex, and it’s a huge needle in a haystack type challenge to figure out, okay here’s a molecule, what the heck does it do? There’s a lot of things going on in a plant. Can you help us understand, how do you narrow down the things in a genome that look promising for discovery in terms of nutrient exposure and growth under harsh condition adaptation?

Elizabeth Sattely: Yeah, there’s a couple things. When you’re doing discovery, the more tools you have, the easier it’s going to be to identify things. Also, the more we know, the more we can start to predict. We’re starting to learn a lot more about the ability of plants to make molecules, and that allows us to say, “Oh, this gene is potentially interesting. We think it’s making a chemical that’s important for a process in the plant.” Furthermore, on the side of tools, we have what’s called model plants, just like in every different system, there’s fruit flies or there’s different cell lines that are important. So we have sort of the fruit fly of the plant world, which is this model plant, arabidopsis.

Russ Altman: Yes.

Elizabeth Sattely: And there’s a lot of tools available to be able to understand and study what are genes doing, what are the chemistries that’s coming out of these plants.

Russ Altman: Tell us a little bit about arabidopsis. Is this something that a normal person would come across in a field somewhere? What is arabidopsis?

Elizabeth Sattely: I call it like a sidewalk weed.

Russ Altman: Okay.

Elizabeth Sattely: You can find it all over the world. There are different ecotypes. It’s very robust. It has a short life cycle, that’s pretty important.

Russ Altman: So you can get your experiments done more quickly?

Elizabeth Sattely: Yeah, it grows quickly, and it goes from a seed to adult plant to seed again very fast. It has a fast life cycle.

Russ Altman: Gotcha, gotcha. So you say that these are small molecules in general, that are secreted. And what is a small molecule to you, as a chemist?

Elizabeth Sattely: I was thinking a little bit about this this morning. You know, proteins are awesome. We know about proteins; they do super cool things. They’re big molecules. For me, a small molecule, I started out as an organic chemist, so it’s something I can draw all the bonds, I can understand the shape. Maybe it has 30 atoms or so.

Russ Altman: Okay.

Elizabeth Sattely: It’s on the order of three nanometers in size.

Russ Altman: Okay.

Elizabeth Sattely: It’s tiny, like a drug, a pharmaceutical.

Russ Altman: Like drugs that we take in vitamins, when you look at the molecular structure, they’re around this size. So one of the things that I know about plants, and it’s not much, is that they have amazing, synthetic chemical abilities. They have abilities to make very, molecules that are even challenging for distinguished chemists to make. And you’ve looked at that, and in some cases you’re trying to kind of copy the ability to match what a plant can do or to almost have a human plant collaboration in making these small molecules.

Can you tell us about what’s special about the synthetic capabilities of plants, and where can we take advantage of this for industrial and medical purposes?

Elizabeth Sattely: Let me start with the first part, what’s kind of special about plants. The chemistry of plants has evolved in a very creative way. Plants pick off the kinds of molecules that are present in every living organism, like amino acids, and can stick them together in all kinds of interesting ways to make small molecules that have a completely new function. So either they’re acquiring iron from the soil or they’re signaling to another cell, which initiates a whole new biological process. In plants, small molecules control immunity. We have cells, circulating cells as part of our immune system. Plants have small molecules that signal to distal parts of the plant.

Russ Altman: Is it fair to say that the small molecule repertoire in plants is greater than the small molecule repertoire in mammals, are they just different or do they have more capabilities?

Elizabeth Sattely: I would say, for sure, plants lean on their chemistry a lot more.

Russ Altman: Okay. ’Cause they can’t move, they can’t do all the things that we do to augment our own ability to basically gather energy, so they have to do it in other ways.

Elizabeth Sattely: Yep, yep. In the way they signal within the organism themselves, signal from one plant to another, the way they communicate cross-kingdom with insects, with pathogens, with humans that might be eating plants. Those are all messages in a chemical form.

Russ Altman: This is The Future of Everything, I’m Russ Altman. I’m speaking with Dr. Elizabeth Sattely about plants and their wonderful capabilities for chemistry.

What about the medicinal or industrial opportunities? I know there are already some. I know there are some famous chemotherapies that are essentially from plants. How do we discover those and is there an opportunity to copy what the plants do to be more efficient and synthetic in our own human synthetic abilities?

Elizabeth Sattely: I mean, we certainly care about plants because it’s the food we eat. Many molecules that are important for human health come from plants. Aspirin is derived from a plant molecule.

Russ Altman: There’s a good one.

Elizabeth Sattely: All the way to, as you said, chemotherapeutics that are molecules we’ve isolated from plants, and then we actually use them in clinic. So, there’s sort of the classical use of molecules from plants as drugs in the clinic, and that’s one major way that plants influence our health.

Russ Altman: Do we actually still get those kinds of drugs? Like, for aspirin, I don’t believe we get it from plants anymore, we synthesize it, but I know that there are some chemicals that are too complex, if I’m remembering correctly, that we actually don’t even know how to make them in the lab, so we have to have the plant as like part of the process.

Elizabeth Sattely: Sometime back, there’s this list, world health organization essential medicines, and if you take a look at that list and ask where do all those different medicines come from, we estimated it was about 10% are molecules that come from plants.

Russ Altman: Okay.

Elizabeth Sattely: They either are exactly the structure that came from plants, or really, really similar. And when you look closely at those cases, the majority are still produced in plants that are grown in the field. The molecule in the clinic started its life in a plant, grown in a field. Or another major way is plant cell culture. So as humans, although we might have the ability to synthesize these from scratch using synthetic chemistry, that’s not necessarily the most efficient way yet to produce them.

Russ Altman: And so when you say in culture, it’s almost like a petri dish with plant cells growing in it, not as a plant but just as a layer of plant cells.

Elizabeth Sattely: Exactly.

Russ Altman: And then you can harvest whatever chemicals you need from that.

Elizabeth Sattely: Yeah.

Russ Altman: Now before we end this segment, I gotta ask. You said that iron was the fourth limiting nutrient. Off the top of your head, do you know what the other three are?

Elizabeth Sattely: Yeah, sure. ’Cause these would be good targets too, I would guess. Actually, they’re very good targets. All you have to do is go to the hardware store and get some fertilizer. So it’s nitrogen, potassium, and phosphorus are the first three most limiting nutrients.

Russ Altman: And any farmer would know this,

Elizabeth Sattely: Right.

Russ Altman: because they’re adding it constantly to their dirt.

Elizabeth Sattely: Right, so nitrogen is another huge input required for plant growth.

Russ Altman: I would gather that these also show a huge variability in their abundance across different types of soil, so therefore, the utility of a piece of dirt, soil, for growth of a plant, might be very dependent on the level of these four nutrients.

Elizabeth Sattely: Exactly, but even though you see large differences in the levels of these different nutrients, plants can grow anywhere, and that’s because different plants have evolved different strategies. Some plants make a home for bacteria that enable them to grab nitrogen out of the air, and that becomes part of their biomass. Other plants can’t do that. So all these cool mechanisms are out there. The question is, what are they, and how can we harness them?

Russ Altman: So now I can link what you just said to the fact that you’re looking at the genomes of these plants, and you’re trying to identify unappreciated molecules that might be involved, now not only in iron, but if you can figure out that there are these parts of the genome that are useful for potassium or nitrogen, that might then expand your research program to look into how are those taken up. Are those all three taken up from soil? Nitrogen might be from the air. So maybe you can give us a quick summary. Are all three of the new ones that are not iron taken up from the soil?

Elizabeth Sattely: Yes, they’re all taken up from the soil. I mean, everything except gasses like oxygen and CO2, and water, are exchanged through a plant leaf. Everything else has to come in through those roots.

Russ Altman: And do you have active programs in all four of those, or is iron the main focus now?

Elizabeth Sattely: We don’t. Think about ourselves, getting our nutrients is only one of the challenges we face every day. We’re interested in how plants acquire nutrients from the soil. We have a project where we’re working on how bacteria can transfer nitrogen to plant roots. But there’s a lot of other challenges of interest to us. Pathogen challenge is another big stressor on plants. How do they combat all of the organisms that they’re essentially bathed in as they’re growing?

Russ Altman: This is The Future of Everything. We’ll have more with Dr. Elizabeth Sattely in a moment on The Future of Everything here on SiriusXM.

Welcome back to The Future of Everything, I’m Russ Altman. I’m speaking with Dr. Beth Sattely about plants, the small molecules they make, and their impact on their own environment and on our environment. So one of the things I wanted to get to is you described very well, how plants are these little factories that are making these small molecules in many ways, much more abundantly and with much greater capability than what kind of we, as human living organisms, can do. But one of the things is, we eat these plants, which means we’re eating these small molecules. Do we know what the impact or importance of these small molecules in plants, that might be uncharacterized R for our health and welfare?

Elizabeth Sattely: I think we’re really starting to scratch the surface in being able to do a good job quantifying what is the role of these small molecules. Much of what we know comes from very large epidemiology studies, with people eat certain foods and have certain disease or health outcomes. But now it’s really time to look much closer, I think, into the molecular contents of that food that we’re eating and have a better understanding of all of these chemicals, this molecular diet that you consume. How does this influence our health?

Russ Altman: So is there an example of foods that we eat that have chemicals with known impact on health?

Elizabeth Sattely: Yeah, one of the most well-studied examples comes from the Brassica family of plants. This is broccoli, cauliflower, cabbage, foods you either really enjoy or really despise.

Russ Altman: Yes.

Elizabeth Sattely: You might really despise them because of the special, small molecules that are made in those food that have a very pungent flavor.

Russ Altman: So the obvious thing, of course, is that the taste of many of our vegetable plants, is gonna be related to the small molecules they contain.

Elizabeth Sattely: Absolutely.

Russ Altman: To the extent that cabbage, broccoli, and cauliflower might have a shared, not only texture, but taste, it might be because of a shared set of small molecules.

Elizabeth Sattely: Right.

Russ Altman: And we actually know something about the significance of those molecules?

Elizabeth Sattely: Yeah, people have been able to isolate the small molecule and do studies with it. There’s data that suggests that consumption of a lot of these vegetables can lead to reduced incidence, for example, in certain cancers. But I think that now we’re really poised to be able to go in ask, in the context of the food, when the molecule’s either there or it’s absent, what is the impact on human health?

Russ Altman: Yes, and I would imagine that, in addition to taste, and this is amazing that there may be some substances that reduce cancer risk in vegetables, because this would just get everybody out there eating more broccoli. I would guess it might have impact on immunity because the immune system is something we don’t fully understand, and I wouldn’t be surprised if these small molecules are interacting with the immune system.

And also, I wonder if these small molecules might have interactions with the bacteria. We’ve been hearing a lot about the microbiome and the bacteria that live in our gut. Do we know if these small molecules are of interest, or are getting the attention of these bacteria that live in our intestines?

Elizabeth Sattely: Yeah, they certainly are getting the attention. I think what we’ve seen in our lab is that gut microbes are able to consume almost anything you put at them, including the small molecules, and they’ll sometimes convert them to different forms that changes the activity of those small molecules. We’re really just beginning to scratch the surface to understand at this chemical level, the reactions that take place in the gut, how do they influence bacteria, and then in turn, how do they influence the human host?

Russ Altman: Really interesting. The issue that would then come up would be the dosage. You say that these studies had been done, for example on broccoli, and it has some small molecules that might impact cancer.

Scientists who are studying this, are they considering the dosage effects? Because sometimes you might find out, well broccoli is good and has a compound that helps you with cancer, but you need to eat 40 pounds of broccoli a day. So I’m sure that there’s a basic question of the quantities of these small molecules and their ability to have biological effects at the dosages, and I’m using scare quotes, because we don’t think of it as a dose, but at the end of the day, if you eat five cauliflower stalks, that’s gonna be a certain dose of a small molecule. Are we getting down to the level of thinking about dosage and what the impact is on individuals?

Elizabeth Sattely: Yeah, definitely. I think like anything, it’s not black and white with these small molecules. It’s likely that they’re good in certain context and at certain levels, but too much of anything is never a good thing. You wouldn’t wanna just go and eat one food in its entirety. The other thing too, is that a lot of these small molecules, the way they’ve been set in the past, is to take them outside of the food context, turn them into more sort of drugs like the kind you would use in the clinic.

Russ Altman: And much purer.

Elizabeth Sattely: Right, and study them there. And we think that there’s likely a lot of different impacts from the food matrix and how that small molecule in compound is delivered and essentially interfaces with the human digestive system. That’s important.

Russ Altman: So studying it in a pure form, may be misleading because it actually is eaten with a whole bunch of other molecules, and that they, as an ensemble, they may have their effects, as opposed to individual molecules.

Elizabeth Sattely: Right, yeah.

Russ Altman: This is The Future of Everything, I’m Russ Altman. I’m speaking with Dr. Beth Sattely about plants.

And we were talking about plants and their small molecules, but there’s another factor here I just wanna ask you about, which is, we often cook our plants. I remember from chemistry lab and biochemistry lab, that when you heat up molecules, reactions happen. I guess there’s a second layer of complexity here, which is there’s the stuff in the broccoli before it’s cooked, and then it might actually be a little different after it’s cooked. Is this of interest, and are there people thinking about what these effects might be?

Elizabeth Sattely: I think that, historically, food chemistry has been kept in a kind of different sphere than us chemists. There’s a lot of reactions taking place when you cook food, when you mix different foods together. Now we’re really starting to understand the molecular processes that are taking place there. But I think that there’s a lot of information to be gleaned about traditional practices, certain foods that are eaten together. What is the actual molecular outcome of doing that and what are the reactions that take place? Why does that occur and why is that helpful?

Russ Altman: So I do watch the Food Network, and some of the best chefs are always talking about, they don’t use the language of chemistry in general. There are some that seem to be trying, but they’re very smart. And, of course, they have a lot of pressure on themselves from the market, to do a good job. And there seems to be, emerging in the cooking industry, some general rules about what goes together well. And what I’m hearing you say is that, there actually might be scientific principles there that can be harnessed to say, a yummy food might be yummy because these kinds of reactions have happened, and that tickles the human palette. Are you a cook?

Elizabeth Sattely: I try to be, yeah.

Russ Altman: And do you find that this is a separate world, or does the chemist in you start thinking about how you’re cooking?

Elizabeth Sattely: It’s always fun when your science life starts to interface with your real life, either in the garden or at the stove.

Russ Altman: Yes, so you do have a garden?

Elizabeth Sattely: I do, yeah.

Russ Altman: So this is actually fun, ’cause it brings together your whole professional and personal life. Do you have a cooking specialty? Here’s a direction you weren’t expecting us to go.

Elizabeth Sattely: No, but I do like enhancing the palette with herbs and spices, things that you grow in your garden, and you know, those are bags of chemicals. Those are drug-like molecules in each and every one of those plants.

Russ Altman: Getting back to this a little bit more scientifically. As you know, one of my interests is drugs and the impact of drugs on human health, and I can’t help but wonder if the small molecules in the food I eat might be impacting how the drugs that I take, the medications that I take, are metabolized or how effective they are. Do we know about the ability of the small molecules in our plant food to kind of compete with, augment, or hinder the effects of our drugs?

Elizabeth Sattely: Yeah, and one of the most famous examples is grapefruit. There’s a small molecule in grapefruit that competes with metabolic processes that would otherwise remove a certain pharmaceutical from your body. That’s just one example, but there’s gotta be lots more out there, because when we take a close look at your salad, what we see is that there’s a huge number of different chemicals in there. I think a lot of what’s happening is currently underappreciated in terms of food, metabolism, and chemistry.

Russ Altman: Yes, and of course I do know about that grapefruit juice prohibition for certain drugs. And I agree with you, that if it’s that big of a deal for grapefruit, the chances that there aren’t lots of other examples of this, and so it’s a hugely important area for human health going forward.

Well, thank you for listening to The Future of Everything. I’m Russ Altman. If you missed any of this episode, listen anytime on demand with the SiriusXM app.


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