Degrading plastics then curing cancer using Aspergillus nidulans with Berl Oakley
Alisa Nappa
 Berl Oakley and his team are using Aspergillus nidulans to degrade plastic and then using the secondary metabolites to then cure cancer, make antibiotics, statins, antifungals and more to save people's lives.
 Talk about killing two birds with one stone. Berl Oakley is the Irving Johnson Professor of Molecular and Cellular Biology at the University of Kansas dedicating the last 40+ years to solving the world's biggest problems with fungi.
 
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TRANSCRIPT
Unknown Speaker 0:11 Welcome, welcome. You are listening to the mushroom revival podcast. I'm your host Alex store. And we are absolutely obsessed with the wonderful, wacky, mysterious world of fungi and mushrooms. We bring on guests from all over the world to geek out with us and go down this mysterious rabbit hole. And today we have burl Oakley, joining us today to talk about degradation of plastics with fungi and producing novel compounds that we can use as humans to help better the planet and ourselves. So burl, how're you doing today? I'm good, good. Thanks for having me on. Yeah. So why don't you tell the listeners what you're up to and what your work is about? Well, I should mention that I'm the Irving Johnson Distinguished Professor of Molecular and Cellular Biology, since a lot of my salary gets paid by the KU endowment, I like to give them credit. Unknown Speaker 1:11 So I've started off as a cell biologist, and we've done a lot of work in cell biology over the last 50 years, which shows you them pretty old. Unknown Speaker 1:25 And then we moved from that we developed a really good gene targeting system for Aspergillus nidulans, which is kind of a model filamentous fungus for our cell biology work. And that sort of led us to some work effect a lot of work on secondary metabolites, which I'm sure you've touched on in this series. Before. That work. A lot of it was done with collaborators, and notably clay Wong at the University of Southern California. And that sort of gradually sort of led naturally in to our recent work on plastics, digesting Unknown Speaker 2:09 plastic breakdown products and so forth. So Clay was involved in that and also Travis Williams at the University of Southern California, both of them at University of Southern California. Unknown Speaker 2:20 And how did your journey begin with both fungi and then Aspergillus nidulans to begin with? Yeah, so it's been a long journey. Unknown Speaker 2:32 I've worked on mitosis and algae in graduate school, and I actually postdoc with RIT Heath, who was doing electron microscopy and fungi. But I continued to work on algae in his lab. Unknown Speaker 2:49 I want to run Morris's lab in 1977. So Ron was developing Aspergillus nidulans as a system for studying mitosis microtubule function. The field was sort of stagnant and his sort of genetic approach seemed like a really interesting, new approach at that time. And so I started working on Aspergillus, in Ron's lab, and I've been working on it ever since. So Unknown Speaker 3:22 do you do you still work with with algae at all? Unknown Speaker 3:27 I don't, I like algae. Unknown Speaker 3:32 But, but no, we don't have some of it's kind of interesting because there's some really fascinating groups of algae. And some of the people that I've worked with in the past have sort of moved gradually to work on things like dinoflagellates, which is what I started out working in the early 1970s. What came to him at a time. Yeah, that's right. Unknown Speaker 3:59 Yeah, you sound like you have your hands full. You know, it sounds like you know, from everybody that I talked to you and even myself, I mean, fungi had as a whole is so overwhelming, even picking one little niche thing. It's so under, Unknown Speaker 4:19 discovered and under study that you can you can pick the most niche thing and have your hands full for five lifetimes. If you want. There's so so much to discover so much to study so much to do. And I recently read your paper, conversion of polyethylene sand to fungal, secondary metabolites paper. Can you give a brief synopsis on what you're studying on this paper? different outcomes, etc. Yeah, so as all of you are listening to will know, plastics are a huge problem. I mean, I don't know how many I think I looked at Unknown Speaker 5:00 How many turns are produced each year, but it's kind of a frighteningly large figure. Unknown Speaker 5:05 And most of them are not recycled, even the some some that Unknown Speaker 5:11 sort of are claimed to be recycled. That is, they're bundled up and shipped abroad. But when they get abroad, they'd sort of pick out the ones that are valuable and dump the rest of them. Unknown Speaker 5:22 So probably five to 10% get recycled. Unknown Speaker 5:27 So that's kind of background. Unknown Speaker 5:31 So Unknown Speaker 5:33 Clay, Wong and Unknown Speaker 5:36 clave, in particular, became interested in this problem, and also Travis Williams, who wasn't working with us at the time, Travis Unknown Speaker 5:44 likes to go out to Catalina Island, and it's on the edge of the Great Northern Pacific Garbage Patch. And that, you know, so part of the island gets a lot of plastic floating in on it, okay. Unknown Speaker 5:59 And there's been a lot of reports over the years where people will go to like landfills or whatever, and find some Unknown Speaker 6:07 organisms, fungi or bacteria that, that have some activity in digesting plastics, but it's really, really slow, right? I mean, they just not practical at all. Unknown Speaker 6:22 So Clay was sort of thinking of looking at looking for things that might digest plastic. And that's it, you should look at the literature plate is going to hit here. Everything so far just says it's forever. And that wasn't the case. But then it occurred to us that maybe we could help out by doing some of the initial breakdown at the plastics using sort of chemical catalysis to break it into things that fungi could use. So Unknown Speaker 6:53 so that's when clay sort of contacted Travis and Travis is a polymer chemist. And so he knows how to break these things down. He was working on Unknown Speaker 7:05 breaking down aerospace composites and stuff. So after they've been used their problem, too. Unknown Speaker 7:13 So we came up with a way of breaking Unknown Speaker 7:18 polyethylene down into smaller pieces. Basically, they're oxidized. So if you think about a chain of carbon molecules, right? Unknown Speaker 7:31 What Travis is able to do is just add oxygen, and then some relatively benign catalysts like manganese and cobalt. Unknown Speaker 7:42 And that catalyzes the breakage of the chain, so it's oxidized. So oxygen, so the the carbon carbon bond is broken, and it's replaced, but two oxygens, one of which has a hydrogen on it, and that's what's called a carboxylic acid, which is kind of a frightening term. But if you think about like vinegar, vinegar is a carboxylic acid, it's not, it's not so Unknown Speaker 8:06 frightening. So you have a carbon, test two oxygens, and then there's a hydrogen when that hydrogen comes off, it becomes negatively charged, so it's an acid. Unknown Speaker 8:19 And so he found that he could treat polyethylenes with oxygen warm, it has to be warmed up and you have to have these catalysts. And it would cleave these changed a polyethylenes kind of at random score Quasar random places, right. And that created a watered dicarboxylic acids that is they've got one acid group at each end, okay. Unknown Speaker 8:47 So so that you know, so broke for the molecule down and there was some literature that said that Aspergillus could Unknown Speaker 8:59 could grow on dicarboxylic acids. The problem is that the small back or back silica acids are one under about 10 in length 10 carbons in length or toxic and so if if you try to grow it on this sort of mixture, you got mixture of the long ones and the short ones and so it doesn't grow very well because the toxic short ones, so they developed a way of making that cut so that you could separate the small ones and the large ones and the smallest out of their own uses you can like make nylon out of them and things like that, but the large ones Aspergillus can use as a carbon source. Unknown Speaker 9:40 fungi and I'm sure you've run into this fungi and Aspergillus in particular are really good at using a variety of foods because they naturally grow in the soil and they have leaves around they have other organisms, worms, or are they just really good at Unknown Speaker 9:59 sustaining the Unknown Speaker 10:00 sells with almost anything that that's around. Unknown Speaker 10:05 So Unknown Speaker 10:08 we found that Aspergillus could grow on these long chain dicarboxylic acids. So we decided to see if we could make anything. So if you just take the wild type strain, it basically doesn't make anything of value Unknown Speaker 10:25 on this, these long chain dicarboxylic acids, but we have been engineering strains to make secondary metabolites. And so Unknown Speaker 10:39 we tried these engineers strain, we even developed a new system, a new promoter system to make the genes that are involved in the production of a particular compound called Astra benzaldehyde. Make it produced a lot more, it's got like a positive feedback loop in it. So it and that worked. And in fact, it worked. Surprisingly well. So if you take Unknown Speaker 11:08 take glucose, your normal carbon source, sugar and grow it, we could make on the order of like two grams of aspar benzaldehyde. Two or three grams of Astra benzaldehyde Unknown Speaker 11:24 per day, from 10 grams of the carbon source. With the dicarboxylic acids we got, with the Astra bins that don't have we got 42% mass recovery, that is we got 4.2 grams, the stuff out of Unknown Speaker 11:42 10 grams of the dicarboxylic acid mixture, which Unknown Speaker 11:48 is, you know, was was staggering. Unknown Speaker 11:51 You know, I figured we'll get a few micrograms or whatever, you got so much, it actually crystallized out, they got to both the limit of solubility and the stuff crystal solution. So it's pretty impressive. It's some of the others secure verad. And it makes more than on glucose and Moodle. And is the other one we did it's it's actually from a mushroom Obsidium. I see. So these are heterologously expressed in the case of sip, revered and mutal. And so we're taking genes from other fungi and hooking them up to promoters so that we can make them be expressed for them in Netherlands and tournaments, turning them on. So yeah, so we were able to make these compounds. And it's kind of a proof of principle, right? And if it worked better than we had hoped for. So I have a bunch of follow up questions for that. The the first being when you were describing, you know, the catalytic digestion process. Unknown Speaker 12:58 It sounded it sounded like a similar process of what fungi Unknown Speaker 13:04 use naturally to digest materials in the wild, like using enzymes like manganese peroxidase. Unknown Speaker 13:12 And using this kind of free radical oxygen mechanism to bind to electrons and cleave large molecules apart, right. Unknown Speaker 13:23 Is, am I right in that assumption that it's pretty similar to how fungi already digest or do a lot of organisms use? I know, like, ozone uses a similar process of using free radical oxygen to cleave things. Unknown Speaker 13:41 Is that pretty common in nature? Oh, Unknown Speaker 13:45 is it common in nature certainly occurs? I don't. I think there's a big Unknown Speaker 13:52 unknown space there, you know, so I don't know whether I'd be comfortable saying whether it's common or not. But if it did, seems likely that same mechanism would be used. The difference is, we're doing it at 150 degrees and with a lot of oxygen. So it goes fast. Yeah, other than the fungus, which is doesn't have the luxury of warming things up to 50. Right. And I'm guessing this isn't like a big, like Biodigester or something. It's it's Yeah, sort of not being done on premises lab is not doing this on a large scale yet. I mean, that's something proof of concept. Yeah, right. Right. Yeah, absolutely. Cool. And then Unknown Speaker 14:39 so I'm trying to wrap my head around these the secondary metabolize metabolites that you're producing, are they Unknown Speaker 14:50 are they the end result after the Unknown Speaker 14:55 after the? Unknown Speaker 14:58 Is it the diacid are Unknown Speaker 15:00 It digested Unknown Speaker 15:03 Yeah, there. Yeah. Are they being used to digest the diacetate? Yeah, that the, we had assumed that that that the acids would be just used as a carbon source to grow the fungus. Right. And so Unknown Speaker 15:22 we had assumed that it that the production of the compounds would be worse than with glucose, because glucose is nice, simple sugar. And so it should grow, as well on glucose is on any thing. Yeah. So it was a surprise that we got higher yields on the plastic breakdown products, the dicarboxylic acids. And that makes one wonder whether there isn't something some sort of shunt pathway or something that's causing more production than you'd get from just growing and then sort of be producing this as Unknown Speaker 16:04 you know, there's the Serbians to Mel O'Neill, Koay, and things like, like that. We don't know that. But Unknown Speaker 16:11 it's really interesting that you get more production on these carboxylic acids, then what you would think would be weird. Yeah. What, what inspired you to, to use that as a food substrate in the first place? And not say glucose? Or any, you know? Well, substrates? Yeah, so so Unknown Speaker 16:37 the idea was to see if we could get some way to break down plastics. And the hope is to be able to break down a lot of plastic. And so this is, you know, Unknown Speaker 16:52 what we came up with this, you know, when we digest plastic, you know, the chemistry of the plastic doesn't give you sort of carte blanche, you've got only a certain number of possibilities. And so they, you know, oxidizing it Unknown Speaker 17:06 gave these dicarboxylic acid, then you sort of look at the literature of weight, you know, Aspergillus shouldn't be able to grow on this. So yeah. So that's, that's where we were kind of on, is there concern of any kind of Unknown Speaker 17:20 toxic residue, or microplastics, or anything like that, or for the, the Unknown Speaker 17:28 it's, it's, you're only using a non toxic part of the plastic residue. I'm not a chemist, so I'm just trying to wrap my head, right. Unknown Speaker 17:40 Yeah, we don't fully know that. So we know that we're able Unknown Speaker 17:47 to digest it, we know that this stuff we feed to Aspergillus is basically dicarboxylic acids. Unknown Speaker 17:56 We know it uses most of it, or much of it to make products. Unknown Speaker 18:02 Plastics have things in them. And one of the problems with recycling plastics is that they have pigments in them. They have Unknown Speaker 18:14 a variety of plasticizers and accelerants and all these sorts of things, most of which you don't really know what they are, because it's sort of proprietary information and stuff. So when we Unknown Speaker 18:32 cleave these things, I'm sure that you know, there's going to be stuff left behind now. It's stuff that, you know, it would be contained. So we could do something with it. It's not like dumped right South China Sea and let nature take its course it's like, you know, we know what we've got, we've got in this and we can see what's in it. And if it's a problem, then we'll try to dispose of it properly lay. Unknown Speaker 19:00 So there's that I think with the fungus growing, a lot of it goes directly to the products and the stuff that does it should be just benign biomass, you know, he should be able to matter, whatever you want to stick it, you know, put it in the ground as compost and stuff like that to be good. So the three compounds that you made Asper benzaldehyde, sit, TREO, verodin to noodle in those three compounds. Unknown Speaker 19:34 Were you intentionally seeking out to make those compounds or was it a discovery on on your part that oh, we get this secondary metabolite? Unknown Speaker 19:46 It was very intentional. Okay, so Aspera benzaldehyde is a compound that we had discovered a number of years ago. So Unknown Speaker 19:58 we've done a lot of work on Unknown Speaker 20:00 secondary metabolites, you know, fungi have a lot of clusters of genes that make secondary metabolites. Most of those clusters are silent under normal lab conditions, so they don't make them. So we've spent a lot of the last 1520 years working out ways to produce the secondary metabolites. Just to digress a little bit. Unknown Speaker 20:24 There's over a million species of fungi. Unknown Speaker 20:29 We started sequencing genomes, we found that they had lots of clusters of genes that are predicted to make secondary metabolites. Unknown Speaker 20:40 And we had no idea there were that many because they're just not produced in, in culture. So you have to figure out some ways to get them turned down. So it's a it's a whole other podcast out there. So the the idea and the proof of concept that you demonstrated is that pretty much any compound that we can imagine we can bioengineer a fungus to not only degrade certain types of plastics, but also create a pharmaceutical factory at the same time, right. So within reason, yeah. So aspirins, aldehyde is actually made by Aspergillus nidulans as an intermediate, so what we did with that was we deleted the gene that stopped the pathway. And so it accumulated, and then we've engineered a promoter system. So that doesn't make microgram quantities, it makes gram quantities of stuff. The scenario viridans is from another species of Aspergillus. And so we engineered that to be expressed in Netherlands and butylene is actually from a mushroom basidiomycete. So, yeah, so Unknown Speaker 22:03 you can Unknown Speaker 22:05 do that? Unknown Speaker 22:07 Well, Unknown Speaker 22:09 so Unknown Speaker 22:12 it turns out, so the big obstacles in this. Unknown Speaker 22:18 So if you, for example, try to get used to produce these things, and so they're not very good at splicing introns. So as some of your listeners may know, many genes in filamentous fungi, most of the genes have sequences in them that aren't, that don't code for protein. So what happens is, when you when the, when the RNA is made, it's then processed, that bits are removed. And so then you wind up with a coding sequence and gives you the right protein sequence. So it turns out that Aska my seats generally use the same mechanism. So you can put genes from other Aska my seats into Aspergillus nidulans, and express them and they're Express correctly, the entrance is price wise correctly, there are almost no exceptions to that. Unknown Speaker 23:17 With basidiomycetes there are more problems, but you know, it's splices most of them correctly, but a few may not be spliced properly, but the middle and Unknown Speaker 23:31 it was placed properly. So you have to change the promoters, but you know, we're really good at molecular genetics and fungi. Now we can do lots of things, too. So we take the coding sequence over you change the promoter and turn the gene on and it makes compounds. I mean, it makes the protein which then can do Unknown Speaker 23:53 to make compounds. I was talking to somebody else about this and they said with fungi, it's it's it's really hard. And they were exploring something called Protoplast fusion. I don't know if you're using a separate process. It sounds like it wasn't difficult for you. Well, so we have been refining the Aspergillus nidulans molecular genetic system for a long time. So we are really good at it specifically with that fungi it's Unknown Speaker 24:26 Yeah, well, it's we Yeah, it's easy after you've worked on it for 20 years to make sure you get better and better like we've we engineered strains that make it easy to transport to get Unknown Speaker 24:42 genes properly targeted so that they almost always go in in the right place. You know, that just does a lot of stuff life but it does work well in our hands. I had an undergraduate that really deleted Unknown Speaker 25:00 or replace the promoters of 125 jeans in let's see in Unknown Speaker 25:07 from January to August when you're working part time, so Wow. That's pretty Yes. Yeah. Yeah, it's like five or six papers, but she graduated from college. Unknown Speaker 25:21 So yeah, it's, it's possible. Unknown Speaker 25:26 Yeah, to put it lightly. So. So these three secondary metabolites that you produced, why why did you pick them? What? What can they do? Why are they useful? And do you have more on the horizon that you you want to target? Yeah. So this is basically a proof of principle, they asked for bins out ahead, is useful, because we'd already shown this clays lab and some other collaborators and stuff. Unknown Speaker 26:01 You can take the asthma benzaldehyde and use it as kind of a platform to modify and the products that one gets, some of them have efficacy. Well, some of them are lipoxygenase inhibitors, which are, it's potentially useful in some types of medicine. Unknown Speaker 26:23 Some of them have efficacy against tau filament. So tau is a Unknown Speaker 26:33 it's a molecule that's associated with microtubules. And you get aggregates of tau in a bunch of dementia like Alzheimer's and Alzheimer's is the best known but Unknown Speaker 26:48 front of temporal dementia and Unknown Speaker 26:52 chronic traumatic encephalopathy effects. And it's not good enough, I think, to Unknown Speaker 27:01 actually use to treat patients but it's, it's been so as per ISO Quinlan, which is derivative of this, so you get the Astra benzaldehyde. And then you can use that modified chemical in a number of ways to come up with with things. So one of them has asked her I said, Quinlan, that's been very useful, because and I don't want to Unknown Speaker 27:25 digress too much on this. But one thing about Unknown Speaker 27:29 tau films, people have tried, you know, people working on dementia is have tried to get compounds that will break down tau filaments, because they're in any of these tau aggregates are in people with various forms of dementia. And they've done a lot of screens. And they get things that seem promising, and then they don't work out now. And to make a long story short, Chris Gamblin colleague of mine, and I was excellent on the paper as well showed that the way that you assemble the tau filaments is important because certain compounds that are good at breaking down filaments assembled in one way or not good and breaking down to fill filaments that are assembled in another way. And Unknown Speaker 28:22 the basic take home message is that if you're going to try to find compounds that are effective against disease, you're going to have to assemble your filaments in a way that's disease relevant. Right? Okay. Yeah. So that's the sort of basic science stuff that's come out of that. Also, some of the things bind to RNAs that bind to proteins that are that are involved in, in, in cancer and so forth. So Unknown Speaker 28:52 so it's you know, that the compounds me first a proof of principle, and in secondary, these are interesting things. Anyway, symmetry of Verdun is Unknown Speaker 29:06 a, Unknown Speaker 29:08 it people, it's toxic, it's a mycotoxin then people wonder if it may be useful in certain types of cancer, chemotherapy. And then they Mulan is sort of a molecule that that can be made into antibiotics. It's another platform molecule. So proof of principle, but you might as well do it with some things that look interesting. And these look interesting. You know, I never thought of using a mycotoxin for cancer therapy. I mean, it makes sense but it's yeah, I you know, if it kills one thing, why wouldn't it kill? Yeah. Yeah, it's super interesting. Unknown Speaker 29:57 Well, you know, if you think about it a little bit like this Unknown Speaker 30:00 statins, you know, like Lova, statin and so forth that are made by fungi in the wild. They're inhibiting Unknown Speaker 30:10 biological processes in there. Yeah. Competitors, you know, and so we just we just use that. Okay, you know, it it Unknown Speaker 30:22 other fungi inhibits kills them with us. We don't take it at doses that kill us. We take doses that didn't have cholesterol by ourselves. Right. So what? What is the quote? Unknown Speaker 30:39 Every medicine is a poison. It's just about dose or something like yeah, I don't know the quote, but it's Unknown Speaker 30:45 right. Yeah. Yeah, that's right. Yeah. Unknown Speaker 30:50 So I think it was in your paper, you were talking about how other researchers were exploring very similar processes. One group of researchers was using E. coli and ended up with the nellen as a end product, which is pretty crazy. Unknown Speaker 31:11 Is is the reason that Unknown Speaker 31:16 researchers might use E. coli versus Aspergillus, the array of of end compounds that you can produce. So Aspergillus can, you know, can't make the nellen but they can make this group of compounds and ecoli can make this group of compounds that Aspergillus can't. Unknown Speaker 31:38 Or levels of degradation. Yeah, so Unknown Speaker 31:44 Aspergillus, various species of Aspergillus make an incredible amount of important compounds, I mean, off the scale, so more than a billion kilograms of citric acid each year is produced by Aspergillus Niger. Okay, I mean, think of us nuts. Yeah. Unknown Speaker 32:07 And Unknown Speaker 32:09 they Unknown Speaker 32:11 produce lipases that are, you know, used in detergents they used and they even used in like, semiconductor stuff, because they take out waxes and stuff. I mean, it's just, you know, Unknown Speaker 32:25 the companies that make these enzymes and stuff, usually quiet about it, because they make a lot of money. And they don't Oh, yeah. Yeah, no, I'm I don't know if you've heard of no designs? Oh, yeah. Yeah, they're huge. I really wanted to do an internship with them. Yeah, unfortunately, I didn't get it. Because I'm, again, terrible at chemistry. Unknown Speaker 32:48 But I would love to to are there, you know, one of their facilities one day, but it's surprising how little that people want to know about them. But fungal enzymes are pretty much in everything. And they're just not really talked about by a lot of people. It's, it seems really weird that it's not talked about more than it is. So thanks for appreciating it. Yeah, definitely. No, it's it's very much the case would you say? So? Novo is one of the Novus times. It's one of the big ones. And then Unknown Speaker 33:25 there was a company called genetica, that was bought by DuPont. And then I think international foods and fragrances. Now, these people don't go to the meetings, and they listen, but they don't you. Unknown Speaker 33:39 Hey, we're making this now. Right, right. Yeah. So the reason I bring that up, in addition to the fact that it's just kind of generally interesting is that Unknown Speaker 33:51 if you're going to didn't make a dent in the plastics problem, you need a potential Unknown Speaker 33:58 use, you need potential uses that are large, right? So but nil, and I'm sure we can engineer Aspergillus to make vanillin. But you're talking about, you know, 20,000 kilos a year or something, right? And so that's not going to, you know, with millions of tonnes of plastic, that's not going to help you get rid of whole lot of plastic. So the notion is that, you know, we could feed into some of these other systems and Unknown Speaker 34:30 use a lot. So I think you Unknown Speaker 34:34 are helping to solve a big problem in the world right now, which is, there's there's lack of incentive for environmental cleanup. And I've talked about this with a lot of people. You know, I think we were trying or we've tried the whole like Carbon Credit Initiative of trying to, we're trying to like monetize sustainability in a way Unknown Speaker 35:00 But which is unfortunate that we have to do that. But it's Yeah, I mean, we have so much mind boggling toxic waste in the world. So like, an astronomical amount of of talk like plastic waste. And at this point, no one's really incentivized to, to clean it up, there's no, you know, I've heard people Unknown Speaker 35:29 they want to include the cleanup costs in the price of the product. And so if it's, if it's really toxic, and there's a lot of toxic end results, that cost has to be one paid for by the company, but also, if it's included in the initial price, customers won't pay for it. And the end result is that there's less of it in the environment. Unknown Speaker 35:54 That's, that's one thing I've heard of, but this sounds to me like, it would incentivize a lot of companies to Unknown Speaker 36:04 yeah, there's there's just an extra incentive another foot in the door to, you know, not only clean up toxic waste, but make things that could, you know, save people's lives. So I think feeding feeding two birds with one one seed, which is great. Unknown Speaker 36:21 Yeah, what what other? Are you primarily focused on pharmaceutical compounds? Or are there are other secondary metabolite, other fields of interest that that you're curious about? Yeah. So a lot of this is, you know, we're sort of again, exploring the possibilities. One thing we have so we've published a second paper in this sort of series where we break down polystyrene into benzoic acid and and Aspergillus can grow on that, it can make some additional Unknown Speaker 36:59 compounds on that. But in addition, we can grow Aspergillus flavus. Own that. So actually, Aspergillus flavus can be nasty. It makes aflatoxin but there is a strain of that, that has a key gene and aflatoxin biosynthesis is a mutant. And so it doesn't make aflatoxins Wow. And so it's actually USDA approved as a bio control agent. That is you put that you put the spores from that owns to what your your corn or, or peanuts or whatever. And it will compete with the the aflatoxin that produces toxins. Oh, wow. Unknown Speaker 37:54 That's awesome. So that that strain at the end of the USDA approved strain will actually grow on the Polish during digestion products of benzoic acid and make spores and so you could you Oh wow. Yeah. So Wow. So there's probably lots of that's awesome. That's really cool. That's really cool. And so Unknown Speaker 38:19 it Unknown Speaker 38:23 I know, I know. Unknown Speaker 38:27 Polypropylene is a big talk right now, it seems like polyethylene 's are, are pretty much the only group of plastics right now that I've heard of that are pretty much feasible to be digested. And kind of more harder plastics, like polypropylene are just at this point and accessible. Is that something in the future? Have you heard of anything that can digest? I know, it's a big group and but yeah, so Unknown Speaker 39:04 we're actually working polypropylene is hard. So polystyrene we've been able to do that works. Well. polyethylenes work well, then you get to things like polypropylene, which are a really good plastics in the sense that they are really tough and they do what they do. Unknown Speaker 39:27 We're trying to Unknown Speaker 39:30 break them down. I mean, we're making some progress, but I you know, it's not it's not Unknown Speaker 39:37 it hasn't been submitted yet. So can't you know, too much detail? Yeah, it's, it's on our horizon. It you know, there's some of these others like polyurethanes and stuff that Unknown Speaker 39:51 are rarely recycled, Unknown Speaker 39:54 as well. So, yeah. The ultimate hope is that we will Unknown Speaker 40:00 Be able to digest mixed plastics. Because if you have to sort out everything, that's a big step, so we probably couldn't digest everything. But if we could, you know, get a bunch of stuff that's useful for the fungus, and then, Unknown Speaker 40:18 you know, the rest of the stuff, figured out how to deal with a lot of plastic is simply burned. I mean, you started looking at this, it's, it's, it's really. Unknown Speaker 40:30 Yeah, so one would hope we could come up with something better for that. But if we could reduce the mass by some substantial amount and do something useful with the breakdown products, that would be great. Unknown Speaker 40:44 Do you think that there is hope for you were talking about ocean plastics in the beginning? Do you think that there's hope to salvage, you know, to scoop up the, the islands of, of trash and our oceans and utilize that? Unknown Speaker 41:07 Well, some of the first stuff we do is actually from the ocean, but they're flooded, like floating bottles and things like that. Yeah. Unknown Speaker 41:16 So that is one of the things that Travis Williams wanted to make a priority was to be able to Unknown Speaker 41:27 deal with, you know, things from the ocean things from you know, not just not just plastics, which are nice and pure from supplier or something like that, you know, you can sometimes get nice reactions and all that stuff. And then when you start doing things in the real world, you're catalysts are poison, then you don't get anything from that. So his procedure is relatively resistance to things like pigments, and so forth, and salt and that sort of thing. So, so that's good. Yeah, I think the biggest challenge there are these microplastics? I mean, how do you I mean, I think we could digest them and use them, but how in the world do you scoop them out of, you know, however, many million square miles of North? Yeah. You know, that's, and not even in the ocean, they're everywhere. I mean, they're in the air, they're just on the surface of everything inside everything. We brought on some plastic experts. Unknown Speaker 42:28 Or maybe a year or so ago, a couple years ago, and Unknown Speaker 42:33 I had no idea that how Unknown Speaker 42:36 unbelievably abundant they are, floating in the air, every breath that we take, I mean, they're literally everywhere now. And yeah, they're like, We can handle the big plastics, but once they're micro level, which is they're varying sizes, but yeah, once, once they're there, there's not much we can do at this point. Hopefully, someone can make a super scrubbing filter for water. Oil, but yeah, yeah, there is. Unknown Speaker 43:10 Work that sort of going on to produce filters for like washing machines and stuff. So that oh, yeah, it stopped before it gets out, you know, so that they will be filled in and filters that are, you know, have small enough pore size to capture the microplastics before they go out. But it's a long way to get there. And these days, but you know, plastics are just Unknown Speaker 43:36 created. So sort of crudely, I mean, it is dumped or whatever, or bundled up and shipped abroad or whatever. So, you know, we're, you know, it's really ambitious to think of filtering out, you know, sort of, you know, five micron bits of plastic. Unknown Speaker 43:54 When we have trouble here, just getting rid of the big bottle. Unknown Speaker 43:59 What, uh, what has been the hardest hurdle for you and your research? Unknown Speaker 44:08 I sort of alluded to this earlier, it's actually been fairly easy this, that's easy, easy after working out it for Yeah, you're developing all of these techniques and so forth over the years, then the last step is fairly easy. You know, if Unknown Speaker 44:25 20 years ago, somebody had said, you need to do this, you need to delete this gene, replace the promoters of this and add another gene here and so forth. I wanted to just sort of say, your well, you know, give me five years. Unknown Speaker 44:40 You're, you're an overnight success after 20 years of hardware. That's right. Unknown Speaker 44:48 What has been your biggest breakthrough moment? Unknown Speaker 44:53 In this area, I think that was probably the surprise at how well the Unknown Speaker 45:00 The fungi produce the secondary metabolites. I mean, I figured they would produce them. But I was thinking, you know, tiny amounts because like crystals partner solution. That's right. That's right. That's awesome. That's awesome. If you had unlimited time, resources funding team, you name it, what what would you do? If anything differently? Yeah, well, I think where we are now one would probably want to try to scale up, they, you know, digestion of these things to see if it's practical, see if you know, how cheaply we can do these things. Because if we can produce these dicarboxylic acids, cheaply, and people can use them, then you know, they will use them. But if, if they're going to cost a lot more than, than their current food, carbon sources, stuff is not going to go go anywhere, I mean, there is a value and intrinsic value and getting rid of the plastic. So that should be figured in somehow. But it in terms of companies using these to grow fungus to make X, Y or Z, they're going to want it to be fairly close to what they are using, now, they're not going to want to pay a whole lot more for it. I think the way to get there is just, you know, see if you can scale up these things, you know, I mean, it would take a lot of money. And, you know, there are process chemists that are just really good at taking this sort of, you know, laboratory device procedures and, you know, making them better and bigger and so forth. So that I think would be where we would need to go to see how practical Unknown Speaker 46:54 This is. Unknown Speaker 46:56 Do you? Do you see that as possible to to you know, replace plastic was, say Unknown Speaker 47:05 petroleum or Atrazine or you know, other toxic compounds? Unknown Speaker 47:14 That certainly it's Unknown Speaker 47:18 hypothetically, yeah. So, yeah. So, for example, Unknown Speaker 47:24 Travis Williams, before he started working on this, he was working on composites, aerospace composites and so forth with some success there. And then there are other things that are likely things that would could look at like motor oil, things like that let you need to get rid of Atrazine. I don't know. But Unknown Speaker 47:51 it Unknown Speaker 47:53 toxic would be the fungus. But yeah, I would say but yeah, I think there's other possibilities there. Yeah. Unknown Speaker 48:03 That's crazy. What do you what do you see as the future of this space as a whole. Unknown Speaker 48:12 So again, sort of scaling up, if you know, if Unknown Speaker 48:17 money if money comes into the field, right? That's, that's one thing. There's an area that I haven't really talked about very much. That's related. And that is, Unknown Speaker 48:32 we generally think of the fungi is like, you know, attacking plastics, so whatever. But some groups have had good success in producing enzymes in organisms so that you can provide them plastic and sort of concentrate, you know, we have a lot of enzymes, you don't just have a fungus, or bacteria and producing a little bit, you just make a lot of that right enzyme so that it can then digest the plastic. That is an interesting approach. Unknown Speaker 49:06 It's, Unknown Speaker 49:08 it'll be interesting to see Unknown Speaker 49:13 what it potential advantage over our approach is, Unknown Speaker 49:19 our approaches it is now is that Unknown Speaker 49:24 now we have to sort of heat up things. So that takes some energy and so forth. If you could run reactions with enzymes at room temperature, let them chew the stuff into something that can be used as a carbon source, that would that would be a great way to go. And there are some people doing that sort of thing. And of course, these days, you can engineer enzymes and stuff, you can get things that don't work so well. But then you start modifying and selecting for things that work better and you know, after a few years Unknown Speaker 50:00 usually get something works really? Well. Yeah. Unknown Speaker 50:05 Maybe a representative Novozymes will listen to Unknown Speaker 50:11 writing down notes right now, or they're already already working on it. Unknown Speaker 50:16 So where can people follow your work and and continue to be updated with all the exciting projects you're up to? Well, I don't do social media very much. My wife is probably good day. Unknown Speaker 50:32 I made a decision a few years ago, Unknown Speaker 50:36 by colleagues, Clay Wong and Travis Williams do a bit, we try to publish and sort of well known chemistry journals. This paper was in the German on Gervonta Chemi, which is the flagship journal of the German Unknown Speaker 50:55 key Chemical Society, these polystyrene paper was in the journal the American Chemical Society. Unknown Speaker 51:03 So we tried to do that. And then Unknown Speaker 51:06 our respective institutions have gotten interested in this. So they publicize some of this work as well, both University of Southern California and University of Kansas. Unknown Speaker 51:22 I'm on ResearchGate. So sometimes when we have a new paper, I will Unknown Speaker 51:28 be Unknown Speaker 51:30 posted that on Research Gate as well. Yeah. And I'm sure there's at least one person out there listening that Unknown Speaker 51:39 has been inspired by this episode. And potentially, is that the point of their life where they might want to pursue this? Unknown Speaker 51:47 How would you recommend they pursue this besides reading your papers? Do you don't know if you open up research assistants in in your lab? Or are there? What can you go to school? To study this? How would someone pursue this? Unknown Speaker 52:07 Well, Unknown Speaker 52:09 certainly, if you work with filamentous, fungi, there are lots of opportunities in biotech companies these days, when I started out, many of my graduate students went into academia and but in the last few years, they are tending to go into Unknown Speaker 52:29 companies. Unknown Speaker 52:31 There's a lot of scope for in these companies like Nova zams, and so forth them Unknown Speaker 52:40 in the the defiant, whatever they're calling it these days. Sometimes it's hard to keep up because, Unknown Speaker 52:48 yeah, changes that are made in the boardroom. So you have a intentional, yeah. The same people, but their badges change at the meeting. Great. Right? Unknown Speaker 53:01 So there's scope for that. Unknown Speaker 53:06 There's, Unknown Speaker 53:08 I think, unfortunately, fungal research is probably a bit underfunded in this country. It China, they're spending lots and lots of money and in Europe, is very interested in fungal biotech Knology, the US has been that we've been the leader in this sort of thing, but we're sort of leaders now, but without a lot of funding. So like, you know, right, in China, they just, you know, it's like, okay, you want to sequence the genome here, and you know, and next day, they got the sequence of what oh, yeah, like, where do you fit? Where do we get the money to do this? Unknown Speaker 53:51 So Unknown Speaker 53:54 yeah, but you know, they're they partment of energy and NSF does fund a certain amount of a lot of Unknown Speaker 54:01 money to be made in the the companies like Novo and stuff. And, you know, that can have a lot of positive outcomes as well. I mean, they're obviously in it to make money but you know, if they can make money and do something useful at the same time, that's a big plus as well. Unknown Speaker 54:22 Yeah, best best of both worlds for sure. Unknown Speaker 54:27 Awesome. Well, you got you definitely. Ah, something for me. I definitely want to go down ADHD research rabbit hole after this and see, you know, I already am so passionate and interested in all the things that fungi can do. And this definitely blew my mind today. So thanks. Thanks for the conversation and the work that you're doing. We need more people doing it because the plastic problem is a huge problem. And if we can make amazing Unknown Speaker 55:00 and things as byproducts that can save people's lives. That's, that's just doubly awesome. So thank you for the work that you're doing. And Unknown Speaker 55:09 everyone read, read his papers, follow his work. And thank you everyone for for tuning in and tuning in for another episode wherever you are tuning in from from around the world. Hopefully you learn something new from this episode. And if you have spread the word, we want more people not only studying mushrooms and fungi, but just connecting with nature as a whole and putting all the great minds together to come up with new solutions to tackle some of our world's biggest problems. And I think the world would be just a better place if if we're just a little bit more connected to the organisms around us, including humans. Unknown Speaker 55:54 And so if you want to support the show, we don't have a Patreon or anything. But we do have a website mushroom revival.com We have a whole line of functional mushroom products from capsules, gummies powders, and they're all certified organic, really good. If you want to win a free product. We have a giveaway going on. We pick a winner once a month. The link is in the bio. We have other resources, free ebooks, blogs, from recipes, cooking things, you name it on our site as well. Including my new book, little book of mushrooms, check it out. And apart from that, I hope everyone has a beautiful rest of your day. Much love and may the spores be with you Transcribed by https://otter.ai
