Fungal Biology-Based Technologies in Biotech Startups

How are technologies from the broad field of mycology being used to build biotech startups? IndieBio hosted an event with mycologists working in cutting-edge technologies, each who described their use of fungal biology in creating innovative products.

Panelists included:

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Watch the event or read snippets of the conversation below:

 

How does your company use fungi to create its products?

We’re very interested in the circular bioeconomy: using lignocellulosic waste from agriculture and industry to create something that can be useful and will biodegrade and return resources back into the system.    —Rachel Linzer, MycoWorks Lead Biologist for Process Development

Mauricio Braia: Michroma is a company developing novel natural ingredients, mainly for the food and cosmetics industry. Our technology is based on submerged fermentation of proprietary strains of filamentous fungi.

There are a lot of industrial activities that produce tons of lignocellulosic waste that are a matter of environmental concern. Our main product is a red fungal metabolite aimed to replace petroleum-based red colorants.

Rachel Linzer: MycoWorks is a biomaterials company that uses the vegetative mycelium structure of fungi to create our first launch product, called Reishi, from mycelium. It can be used in leather-like applications. Like Mauricio, we’re very interested in a circular bioeconomy: using lignocellulosic waste from agriculture and industry to create something that can be useful and will biodegrade and return resources back into the system.

Kevin Chen: At Hyasynth, we engineer yeast to produce the active compounds of cannabis. Our yeast uses enzymes that come originally from bacteria, other fungi. and even a protozoan. We take a yeast from the fungal world with bacterial enzymes and use that to make a plant product: we’re all about cannabinoid biosynthesis.

Cannabinoids have been shown to be really important products in medicine, health, and wellness. Right now, growing cannabis is cost prohibitive; there are a lot of challenges in growing that plant at large scales. We like this system because it’s an industrial fermentation and there are industrial fermenters all over the world.

Christopher Kong: The food system of the world is broken; we produce excessive greenhouse gases as well as biodiversity collapse through extensive use of land, driven largely by the meat industry. So at Better Nature, we provide protein without compromise.

We do this by leveraging an ancient technology, a fungal fermentation called tempeh fermentation. It originated in Indonesia 300 years ago and is still widely eaten in Indonesia but has failed to gain mainstream appeal in part because of limited creativity around the use of tempeh fermentation. We’re the world’s first foodtech company focused on this process; by using our proprietary blend of starter cultures and our proprietary blends of substrates, we’re creating the alternatives that look, cook, and taste just like meat using the fermentation process.

 

What convinced you that fungal technologies uniquely solved the problem you were addressing?

Filamentous fungi have natural features that make them great for submerged fermentation, and we think that in the coming years that filamentous fungi will become major biofactories.     —Mauricio Braia, Michroma CSO

Christopher Kong: One of the main challenges when creating protein alternatives is: how to create the right mouthfeel?

If you use pure plant-based sources, you run into all sorts of different problems. A really cool thing about fungal fermentation is that you inherently get that texture from that fermentation process, so you bypass a lot of the issues with trying to emulate or recreate that structure post-fermentation or post-process. 

Mauricio Braia: Our technology is a submerged fermentation instead of a solid state fermentation. Filamentous fungi have natural features that make them great for submerged fermentation, and we think that in the coming years that filamentous fungi will become major biofactories to produce ingredients and molecules: they have natural secretions systems, they can naturally produce secondary metabolites, some of which are toxic for yeast or bacteria. There are a lot of advantages within the filamentous fungi that we believe make them the future of fermentation.

Kevin Chen: The broad strategy when it comes to thinking about secondary metabolite production is to examine the metabolism of different organisms you want to use, different yeasts or different materials and choose the one that makes the most sense or has the thing closest to your target product. For yeast in particular, you do have a pretty wide selection of metabolisms to play with and the existing infrastructure and tools and methods to do engineering with the genome as well.

The big difference between today’s era of genetic engineering versus the 1970s when insulin was first produced in bacteria is that nowadays you can work with fungi with super high-throughput tools like DNA synthesis to make a lot of gene edits and really play with the metabolism of these organisms. 

 

How to systematically determine which fungi are best for scaling production needs?

Christopher Kong: It’s very different developing the technology at the bench and growing to the industrial scale, especially with food. There are so many regulations and so many health and safety measures that need to be controlled for. For us, the appearance of the end product is a big issue, and typically when a fungi sporulates they become black, which can be quite unappealing to customers. For us, finding a strain to resist that sporulation and yet still grow quite quickly and resist heat stress, water stress, and moisture stress was quite important. 

A lot of our decisions were guided by bench top analysis of the nutritional as well as sensory profile of the end product we wanted to create, so it’s been a bit of both: a bit of picking the right strains that can create the optimal product and controlling for the fermentation conditions to create a product at scale, to do it efficiently and reliably.

Mauricio Braia: When we talk about scalability, we are working with bioreactors. In terms of the technology, there are a lot of bioreactors in the industry and available for scale up. Working with filamentous fungi can be very challenging but there is a lot of knowledge around some species, like Aspergillus, Penicillium or even Fusarium

One of the reasons we decided to use filamentous fungi is because of the alternative feedstocks you can naturally use with these fungi, even if you are working in submerged fermentation. You can use agro-industrial wastes, which is an appealing feature. The most difficult part of working with these filamentous fungi is not the fermentation but is the strain engineering.

Rachel Linzer: In biomaterials, you’re not using your fungus as a factory to make something else, but your biomass is actually your product. It becomes a complex interplay between the material properties of the filamentous fungus, the aesthetic properties, the fermentation speed, and the feedstock. You have to find a bio-safe fungus if you’re not going to purify the product from the fungus; if people are in physical contact with the materials, then you want to make sure that safety is a big part of strain selection.

 

Where is the future of mycology technology headed?

The ability to control and manipulate biology means that you can invent new things as well: it’s one of the things that most excites me…you will have brand new colors, brand new kinds of tempeh, and brand new materials that you can’t even imagine now.    —Kevin Chen, Hyasynth Bio CEO

Mauricio Braia: Filamentous fungi are going to be key to produce materials, foods, for use as a factory and for remediation. They’re going to be key to tackle all the challenges that you might have in the near future; I can’t imagine a place where they won’t have a crucial impact. Today, filamentous fungi are used to produce enzymes and antibiotics and other molecules—I think that the spectrum will quickly become much broader.

Rachel Linzer: It’s a really exciting time to be in the biomaterials space, but also to think about other applications for fungal biology as we have the molecular tools to understand fungi and fungal relationships. In addition to the amazing materials, we can also start exploring the contribution of mycorrhizal fungi to agriculture and the contribution of microbial consortial to flavor profiles and robust response to climate change. 

There are so many applications that we’re just starting to touch on and things we haven’t even talked about today, or don’t have represented here today. We can identify fungi, we can see where they are and what they’re doing, better than we ever could before. 

Kevin Chen: Look around and see how many things weren’t made by fungi—then imagine a future where everything is made by a fungi! Sustainability is a great benefit for the biological synthesis of things. 

The ability to control and manipulate biology means that you can invent new things as well: it’s one of the things that most excites me. Of course we can produce specific cannabinoids, but we can also produce new kinds of cannabinoids that cannot be made by nature. You will have brand new colors, brand new kinds of tempeh, and brand new materials that you can’t even imagine now.

 

Thanks to Kevin Chen, Rachel Linzer, Mauricio Braia, and Christopher Kong for their participation.

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