- Open Access
Recent advances in the intellectual property landscape of filamentous fungi
Fungal Biology and Biotechnology volume 7, Article number: 16 (2020)
For centuries, filamentous fungi have been used in the making of food and beverages, and for decades for the production of enzymes and pharmaceuticals. In the last decades, the intellectual property (IP) landscape for fungal technology has seen an ever increasing upward trend, introducing new and promising applications utilising fungi. In this review, we highlight fungi-related patent applications published during the last 5 years (2015–2020), identify the key players in each field, and analyse future trends. New developments in the field of fungal technology include the increased use of filamentous fungi as a food source (mycoprotein), using fungi as biodegradable materials, in wastewater treatment, in integrated biorefineries and as biological pest agents. Biotechnology companies in Europe and the US are currently leading when it comes to the number of patents in these areas, but Asian companies and research institutes, in particular in China, are becoming increasingly important players, for example in pesticide formulation and agricultural practices.
Fungi are eukaryotic organisms that have characteristics of both plants and animals but are placed in a distinct kingdom . Fungi in general can be microscopic to macroscopic, and include unicellular organisms, such as yeasts, and multicellular organisms, such as filamentous fungi. Filamentous fungi grow as long, 2–10 μm thin filaments (hyphae) into intricate network structures (mycelium) that are observable to the naked eye and can grow to centimetre- to metre-scale. Filamentous fungi represent an incredibly rich and diverse group of species, with tens of thousands of fungal strains that have been identified, characterised, utilised and modified to this day. There is significant growth in the number of catalogued fungal strains, with an estimated 95% of fungal species estimated to be undescribed yet , and the scientific community is building an increasingly vast body of knowledge around these complex and valuable organisms. The large and growing interest in filamentous fungi mostly stems from the fact that their metabolic processes can be used to produce and refine a wide range of products and solutions  that create value for science, industries, and consumers.
Filamentous fungi, along with other microorganisms such as bacteria, yeast and algae, have been proven to be very useful for industrial applications . Historically, their metabolites have created massive values in areas ranging from pharmaceuticals  to cosmetics  and commodity chemicals , and the production of these metabolites has had significant impact across the entire biotechnology spectrum. Starting with breakthrough developments of antibiotics in the early twentieth century, filamentous fungi have since then been used for applications that include producing biological control agents, enzymes, alcoholic beverages, organic acids, food and feed [8, 9]. With the rapid developments in strain discovery, strain engineering and industrial product development, it is certain that filamentous fungi will continue to be a key contributor in the creation of a biotechnology-based future.
Filamentous fungi and intellectual property rights
As a result of these breakthrough solutions taking shape, activity in the intellectual property (IP) space is increasing as well. As the value and potential of filamentous fungi become more and more established and recognised, efforts to capture and control that value through the use of intellectual property rights (IPRs) have intensified across the globe . Patents are arguably the most important IPRs for protection solutions, and the landscape unveils a growing body of patents surrounding novel processes and products related to filamentous fungi. This is indeed a strong indicator that international markets are realising the great potential that these organisms have, and that key industry players are doing what they can to secure value creation and value capturing through the use of IPRs.
Protecting filamentous fungi and other microorganisms with patents and other IPRs is challenging for two reasons. The first reason is that inventions relating to biological material are, by their nature, much more difficult to disclose than inventions in other areas. Patent law requires that a patentable invention be disclosed in a manner elaborate and clear enough so that a person skilled in the art can carry it out. With inventions relating to microorganisms, such disclosure is usually impossible. The Budapest Treaty, first signed in 1977 and entered into force in 1980, attempts to circumvent this problem by allowing instead for depositing samples of biological material to recognised institutions [11, 12]. Thus, all patenting procedures of new and modified strains of microorganisms, including filamentous and yeast-type fungi, follow the provisions of the treaty. The second reason is that much of the legislation around patenting of microorganisms is highly bureaucratic and difficult to comply with . An example can be found in the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement, whose provisions are well-known among industry players as very challenging to understand and live up to. A range of other issues have been created as a result of the ratification of TRIPS, all of which deserve analysis and discussion, but for the scope of this report it is sufficient to mention that many challenges are present.
Clearly, protecting technology surrounding filamentous fungi with patents and other types of IPRs is not an entirely easy ordeal. To truly realise and capture the great potential value of filamentous fungi, these challenges need to be thoroughly understood and taken care of. Related to this fact is that any industrial player should be mindful and attentive of past and current trends within the patent landscape of filamentous fungi. Despite the clear importance of filamentous fungi in developing ground-breaking biotechnology, efforts to summarise the critical and current IPR trends around filamentous fungi is lacking. This report therefore sets out to provide a thorough analysis of the recent patent landscape surrounding filamentous fungi and its various (industrial) applications. In addition, we seek to identify the key global players in the most important markets, and to make predictions about developments within this technological area for the coming years.
Before analysing more specific fields of application, we will discuss the general patent landscape regarding filamentous fungi. First of all, it can be clearly seen that there has been a considerable increase in publications of patent families discussing filamentous fungi starting in 1990 (Figs. 1 and 2a). For the patent search and analysis the software Orbit Intelligence (Questel) was used (details in “Methods” section).
The top 5 players in terms of numbers of patents in the field of fungal technologies over the last 30 years were Novozymes (311), Dupont (289) incl. Danisco & Genencor, DSM (133), Meiji Holdings (44), and AIST (38)—International Institute of Advanced Industrial Science Technology. All are established biotechnology institutions that provide biological solutions for a variety of applications. The major technology areas over the same time frame were the following: 37.6% biotechnology, 15.0% basic chemical materials, 10.9% food chemistry. The majority of the patents categorised as biotechnology were found within the subgroup of enzymes and microorganisms.
During the last 5 years the distribution of patent classification in the field has not changed much, with 36.8% of patent applications being classified as belonging to the domain of biotechnology, while 15.7% were classified as basic materials chemistry, and 10% as food chemistry. The biggest observable trend concerned the countries of origin of patent applications. Here, an increase in patent families originating from Asian countries (mostly China and Japan) was noticeable. The key players of the last five years were: Dupont (137) incl. Danisco & Genencor, Novozymes (99), DSM (57), Toray Industries (24) and Dalian Institute of Chemical Physics (23) (Fig. 2b).
In the following sections, we describe the patent landscape in seven different subfields. Selected patents do not represent a complete list of published inventions, but instead were chosen to give an overview of the trends in the field and highlight important developments.
Food and feed
Fungi have been used all over the world for millennia to produce various fermented foods and beverages [14, 15]. Traditional fermentation processes involving fungi and yeast are for example used to create soy sauce, miso, tempeh, “mould-cheeses” and beverages like beer, wine and spirits (Table 1). Mushrooms, the fruiting bodies of fungi, are of course also an important food, with the global mushroom market estimated to be worth over USD 42 billion . However, in this study we did not include applications and inventions related specifically to mushrooms.
Because of the many challenges related to global supply and demand for food, biotechnology has become an increasingly important solution for creating ways to feed the world. More recently, during the last decades, different microorganisms such as bacteria, yeast and algae have been heavily researched for their ability to create various types of biomass and compounds that can be used in production of food and animal feed [17, 18], with filamentous fungi being no exception, as they can produce a variety of useful food ingredients like enzymes, fatty acids, flavouring, organic acids, pigments and vitamins (Table 2).
Within the area of food and feed applications, three main patenting sub-trends could be identified: production of food additives, using fungi as the main ingredient in new food products and using fungi for production of animal feed. All patents mentioned in this section can be found in Table 3.
Looking at the patent landscape regarding food additives and filamentous fungi it could be seen that most patents relate to the production of enzymes or other compounds by either using a fungus as recombinant production host (i.e. inserting genes into its genome to produce new substances), or by using specific metabolites or enzymes native to the fungus. Filamentous fungi are highly important for their ability to selectively produce certain compounds of interest than can be used for areas such as nutritional supplementation, dyeing, and texture improvement. To name just a few examples of this, the patent landscape revealed new methods for producing sweeteners like steviol (EP3063286, WO2019006244A1) and other flavouring agents like sesaminol (WO2018/056388), as well as special dietary proteins (CN110746494) and a range of vitamins and minerals. Even some enriched nutritional products that include the whole fungi biomass have been developed, such as an iron supplement made with Aspergillus oryzae (EP3462915) or fungi that are enriched in vitamin D through UV irradiation (US20180021405). When looking at proteins and enzymes as food additives, the patents focus mostly on ones that improve textures and processability of materials, such as glucose oxidases for baking processes (EP3182829), xylanase to improve the storage of crisps (EP2869701) or ice structuring proteins to improve the freezing process of foods (EP3302076).
Even though fermentation with filamentous fungi has been used in food production for a long time, there are still improvements to be made. Accordingly, there was a surprisingly high number of new patents that relate to traditional food products and traditional food production processes. Improvements include hydrolases to increase soy sauce production (JP2016136843A), pre-cultures for faster koji production (US20190159495) and tea fermentation (CN107494809), removing off flavours in rice wine (KR20180055255), increased fermentable sugars in beer production (WO2019/067287) and better production of tempeh and other fermented bean-based foods (JP2016123395, JP2019129802).
One area that has seen a noticeable increase in patent applications in the last years is the production of food products that contain biomass or proteins of filamentous fungi as a or the main ingredient. Often, the application of the fungi here is called mycoprotein or, if the target area is animal feed, single cell protein (SCP). So far, there are only a handful of players in this field, but the trend certainly points towards an increase in this segment. The reasons for this are the high demands by consumers for more variety in the vegetarian and vegan product segment (e.g. to have an alternative to soy), the general increase of vegetarian and vegan products on the market, as well as the increased knowledge about the nutritional advantages and benefits of fungi-based protein. Mycoprotein is becoming an increasingly popular alternative to meat and even to meat alternatives like soy and pea, due to a very favourable amino acid profile and texture. We also identified examples of inventions related to further improving the attractiveness of filamentous fungi as a nutrient source by boosting the contents, ratios or availability of nutrients, as discussed below. One of the earliest patents in the area of mycoprotein were filed by Marlow Foods and describe production of what is now known as Quorn. Even though the original patents were filed in the 80ies (e.g. EP0804086), continuous improvements and inventions have been made, such as different ways to bind the proteins together (EP3474685) or reducing RNA levels in the final product (WO2018/002581). In recent years, the landscape has diversified, with more actors starting to file patents in the sector, in particular companies and organisations from Sweden, the UK and the US. They differ mostly in the use of different edible fungal species; while Quorn-related patents typically only use Fusarium venenatum, others use Neurospora crassa (WO2019/121697, US20190373934) or Zygomycete species (Rhizopus oligosporus, R. oryzae). We saw a clear indication that actors are moving to develop and protect more industrially focussed processes. Examples include patents that describe a possible integration of production of filamentous fungi for food (and feed) applications with bioethanol production (EP3464555, EP3080282, EP3209789). Furthermore, most patents describing mycoprotein production use a form of submerged fermentation (WO2017/181085), but some actors developed solid-state or surface-growth fermentation (WO2019046480A1, US20200268031A1).
Patents related to animal feed are mostly focussed on improving the digestibility of feed for the animal (IPC code A23K+). Most of these patents are protected in China and an increase has been seen in the last couple of years. Interestingly, many of the patents in this category can also have applications for human food, but do not necessarily mention this in the patent, nor is the patent categorised in human food applications.
Many examples of new patents related to animal feed, as will be expanded in more detail further below, were enzyme-related patents, such as the production of mannanases (EP3385376) and xylanases (WO2020/009964), as well as enzymes that break down fish guano for aquafeed (CN106805002). Other areas were related to preparing functional feed additives by using fungal fermentation (CN108450656, CN109497259). Pet food is another area where IP regarding filamentous fungi has increased in the last years, either as supplements produced by fungi, or as the whole fungi biomass to produce vegetarian pet food (CN108719578).
Historically, food-related applications of filamentous fungi have mainly been developed within the world of academia, however nowadays the landscape is dominated by established biotech companies which produce enzymes used in the food production. More specifically, of 324 identified relevant patent families in the field of food products, 38% were owned by the top 10 organisations. The key players from the last five years were DuPont (47 patents), DSM (16), AB Enzymes (13), Novozymes (11), Toray Industries (10). Marlow Foods had seven patents solely related to meat alternatives based on filamentous fungi. From a geographical perspective, the majority of patents were filed in China, closely followed by Europe, the US and Japan. Patents originating from Asia heavily focussed on traditional fermentation products, such as those of Kikkoman and Yasama, while Europe and the US focussed on patents related to the protein shift towards mycoprotein as a complete food source.
The economic significance of filamentous fungi to the pharmaceutical industry cannot be overstated. Fungi have been widely exploited due to their capacity of producing a wide range of valuable compounds. Antibiotics, small molecules that inhibit the growth of microorganisms, in particular bacteria, are probably the best-studied fungal secondary metabolites . However, although over a thousand antibiotic substances have been discovered in the past decades, less than around a hundred have been granted permission by regulatory agencies to be used in humans and animals, due to their toxic and adverse effects . Most currently available antibiotics of fungal origin are found within the Aspergillus and Penicillium groups. Other fungi-produced pharmaceuticals include immunostimulants, anti-infectives, immunosuppressants and statins.
To identify the most important trends related to the production of antibiotics and other pharmaceuticals, we considered activities both within the healthcare sector, as well in sectors like agriculture and animal husbandry. The contents of recently published patents revealed for example that the growth inhibitory activity of certain antibiotics can be used against agricultural pests such as nematodes, arthropods and other parasites (EP3058939). Other compounds related to agricultural use of pharmaceuticals included biological fertilisers (CN107828699) and pesticides (WO2017188049), as well as fungal extracts that fight bee colony collapse disorder (US9474776B2).
In the healthcare sector, patents describing fungal technology were found for diverse applications, from biomaterials for the treatment of wounds (EP3165233) to products inhibiting the growth of oral bacteria in humans (WO201965124). Most new inventions, however, were not related to native fungal compounds, but to compounds produced in fungi as a production host, and are therefore related to the optimisation of cultivation techniques by genetically engineering the fungus (see also “Fungi cultivation methods” section). These included the production of antibodies (WO2019/175477, CN109575130, CN110256557) and glycan-based antibody-drug conjugates (EP3426288, US2017036233), the improvement of the production system itself (EP3004145), or the transformation of compounds through fungal fermentation (EP3442553) (Table 4).
Overall, large organisations were not as prevalent in the pharmaceuticals field compared to other fields in this study. In the performed patent search, 23% of patents could be assigned to the top 10 organisations, the most prominent being Merck, Alder, DuPont, CNRS and Novozymes. While most of these are established biotech/pharmaceutical companies, a lot of IP was generated by universities and research centres such as CNRS and Shandong University, both of which are also among the top 10.
The production of bulk chemicals—such as low molecular weight organic acids—by filamentous fungi has attracted considerable attention due to their industrial applications. The demand for sustainable alternatives to petroleum as a source of fuel and a precursor for chemicals is high and has driven advancements in synthetic biology, genetic engineering and microbiology. Filamentous fungi are natural producers of a variety of molecules with potential applications. In addition, some species are capable of a high production of organic acids (e.g. citric acid, AU2008223787B2, US20150232892A1), which are often used as food additives and cosmetic ingredients. Organic acids are fully biodegradable molecules and can also be used as chemical intermediates for the production of biodegradable polymers. Furthermore, filamentous fungi are used to produce dyes, artificial aromas and flavourings. Chemically speaking, these include a wide range of aromatic molecules, polypeptides, oligo- and polysaccharides and phenolic compounds (US9637763, EP2754716, CN107987183). An interesting feature of the literature around fungi-based production of organic acids, and also of the patents covering the same, is that it is often sharply focused on the ability to produce individual compounds, and not so much on the general production processes of the fungi.
The wide variety of applications of organic acids was well reflected in the patenting landscape of filamentous fungi. Several patents disclosed novel methods for production and uses of C4-dicarboxylic acids (WO2018051837A1, US2013288321, EP2473600B1, US20150104543A1) which have the potential to create commercial value in several ways. Other patents disclosed fungi-based methods for production of oxalyl-CoA, glyoxylate and glycolic acid (WO2019020870A, US9783809B2) and fumaric acid (WO2017110970A1). We detected an increase in patents related to fungal production of itaconic acid over the last years. This acid has gained recent interest as a future bio-based platform chemical [21, 22] and efforts are being made to increase space–time yield and the fungal production system (EP2183367B1, WO2014142647A1, WO2017074533A1, WO2018037123A1, US10443077B2, CN105274153A). Other developments lie in the integration of different production processes and the use of low-cost raw materials (US20190360004A1). All patents mentioned in this section can be found in Table 5.
As with other trends described, major biotechnological industry players were prominent in this field as well, such as Novozymes and DSM. There were, however, organisations who are less active in other use areas of filamentous fungi that were present within this patenting space. Examples are companies such as RHO Renewables, KAO and Shonan Technology Center. On the academic side, we saw a strong presence of biology-oriented research institutions such as the Technical Research Centre of Finland (VTT).
The advances in fungi and enzyme research have had fundamental implications for industrial biotechnology . Filamentous fungi are natural producers of a variety of different enzymes and are excellent at secreting them into the culture medium. For that reason, they are often successfully used as a chassis for the development of recombinant production strains. Again, this area is indicative of the incredible versatility and flexibility that can be obtained by using filamentous fungi for the production of various compounds of interest, and we saw a very wide range of topics and inventions covered in the patent landscape of fungi-based enzyme production (Table 6).
Many disclosed inventions related to the production of specific enzymes, in particular lignocellulolytic enzymes, and related compounds of interest, such as laccases (EP1799816, WO2012023021A1) xylanases (EP3099794), phytases, cellulases (EP2766471, WO2019122520A1, WO2019219804A1, WO2016090474A1), amylases (EP2906692), mannanases (EP3385376) and lytic polysaccharide monooxygenases (LPMOs; WO2016142536A1) to give a few examples. As would be expected, these patents have diverse application areas, and there are clear connections to industries ranging from pharma to food to pulp and paper. Competition between actors producing these enzymes can be high, as the patent landscape revealed several patent disputes and invalidity actions between some of the strongest companies working within the field. This is perhaps not entirely surprising, as this part of the market space is inhabited by organisations with high levels of IP sophistication.
The main fungal production hosts have not changed much in the last decades, and were also in the selected patents mostly limited to Trichoderma reesei and Aspergillus species.
In the area of processes for enzyme production, patents were heavily focused on the general ability and potential of filamentous fungi to produce enzymes for a vast variety of purposes. The patents related to this field will be discussed in more detail in “Fungi cultivation methods” section.
Among the most prominent developers of fungi-based solutions for enzyme production is Novozymes, a leading Denmark-based biotechnology group. AB Enzymes stands out as a rising actor within the field, having filed several significant applications during the last few years. Other renowned names from the biotechnology space, such as Dupont, DSM, Codexis and Toray Industries, appear in the records as well. Academia is of course also well represented, with reputed organisations such as the Technical University of Denmark (DTU), India’s Council of Scientific & Industrial Research, VTT and Nagakoa University of Technology showing up repeatedly.
The domain of environmental technology holds a variety of inventions, with most patent inventions being associated with treatment of water (wastewater, sewage or sludge) or biological processes for separation. There has been a significant increase in inventions in this technical domain in recent years.
Interestingly, the area of using filamentous fungi in wastewater treatment is predominantly protected in China. In most of these inventions, fungi are integrated in the solution either as biomats or microbial sludge (US20190316077, CN206886941U, CN109370943, CN109092048, WO2018/014037). However, some patents were identified where enzymes from filamentous fungi are used, such as cellulases (EP3219797) and amylases, to break up compounds in the waste stream. Recent patents also included examples of degrading solid waste and transforming it into something with more value (CN108219887, EP2576213). The mentioned patents can be found in Table 7.
Most of the patents we analysed that fall into the area of biological water treatment were filed and protected in China (around 70%). The key players were Asia-based universities such as Central South University, Beijing University of Technology and Hohai University. Currently most patents are coming from research-based institutions, as it is still such a recent field. Another reason why the adoption by companies has not been as fast as in other segments is perhaps that it is not quite as straightforward to make money from wastewater treatment as it is through production and sales of chemicals, enzymes or pharmaceuticals. However, it is expected that in the future more companies will enter this landscape due to governmental incentives, penalties for environmental pollution and increasing value of clean production processes.
Fungi cultivation methods
To keep up with the rapid developments within all aspects of filamentous fungi applications, the methods and tools for cultivation need to improve accordingly. It is clear from the patent landscape that companies and public actors are seeking new ways in which we grow and manage these interesting microorganisms. Different needs sprout these solutions, but the common goals to improve fungal cultivation have to do with increases in titre, rate or yield (TRY) of the process in question, as well as the efficient genetic modification of the production strain. Two main patenting sub-trends were identified: one that relates to novel cultivation techniques and molecular biology methods, and one that relates to physical equipment for improved production.
In the subcategory of novel cultivation techniques fall patents that deal with metabolic and genetic engineering, as well as the ways that fungi are cultivated, maintained, manipulated and stored. Examples include methods for continuous production of filamentous fungi (FR3071507), innovative solutions for producing fungi pellets of extraordinary density (WO2018/221482), novel biomat formation (KR20180117131A) and changing the viscosity phenotype of the organism (EP2673290). Furthermore, several novel processes have been disclosed in conjunction with the product patents described in the section below.
As mentioned above, inventions in the area are also focused on the ability and potential of filamentous fungi to produce enzymes for a vast variety of purposes. In this regard, many patents describe methods for modifying the fungal strains themselves at a molecular level. Examples include, but are not limited to, methods for continuous enzyme production (FR3071507), general genome editing applications using CRISPR-Cas9 (JP2018525983A, US20190194692A1), regulating gene expression in fungi and improving protein production or secretion (EP2576793B1, US9499826B2, US9512415, JPWO2017170917A1, CN109661402A, JP2018504936A), and using genetically modified filamentous fungi for producing various biosynthetic products (EP3004145).
In the area of cultivation equipment, the majority of patent-protected inventions relates to physical tools. These include new vessels for efficient fermentation of filamentous fungi (CN207062292), equipment for mechanical control of filamentous fungi ball size (CN108893254) and devices for maintaining fungal cultures (CN209002501U, CN109628275). In contrast to other microorganisms, filamentous fungi often form mycelial macrostructures during cultivation, and depending on the process this can be either a benefit or a challenge. Aside from aspiring to improve fungi cultivation in general, we interpret this apparent demand for improved hardware as an increasing interest in integrating fungal cultivation solutions into existing industrial infrastructure. All patents mentioned in this section can be found in Table 8.
There was not a particularly strong presence of the otherwise dominating actors in this particular field, even though they were present (e.g. Novozymes, Dupont, KAO). Rising in this landscape was AB7 Industry. However, most inventions relating to cultivation methods and equipment came from within academia, with organisations such as Shandong University of Medical Sciences, Lingnan Normal Universitym, VTT and Jiangnan University appearing repeatedly.
A nascent field that is picking up momentum is the application of mycelium of filamentous fungi as a material. Pure, composite and cross-linked mycelium materials have been created, as well as polymers of mycelium and fungi-derived chitin–glucan films. A recent paper by Cerimi et al.  gives an overview of patents that cover the production or use of fungi as biomaterial between 2009 and 2018. Recent patents describe fungi biomaterials that include textiles (CN106758447B), insulations (US10407675B2, WO2018120823A1), packaging (CN108249037, US20180148682), leather-like materials (CN102329512A), composite materials (US20190090436A1, US20130202855, US20190390156A1, US20190284307A1), as well as methods on how to achieve these materials (US20200196541A1, WO2020115690A1). See Table 9 for more details.
In most cases, the mycelium is grown into molds or as a biofilm, inactivated, dried and processed to become a stiff or elastic material. A variety of different fungal strains, mostly Basidiomycetes such as Pleurotus ostreatus and Ganoderma lucidum, were mentioned in the associated patents.
The recent patent landscape for fungi-based materials is still fairly small with only four main players, three of which are US-based companies: Ecovative (21 patents), Ford (9), Shenzhen Technical University (8) and Mycoworks Inc. (3).
Because of the constantly increasing demand for food, and the many challenges facing the food and feed industries, we believe that microbiological, and in particular fungal, solutions for the production of food products and nutrients will become ever more important in the future. While other microorganisms show great promise for rising up to the challenge as well, filamentous fungi have excellent prospects for assuming the role of the single most important source of microbial nutrition. This is related not only to the already high degree of consumer acceptance, but also to the robustness, (substrate) versatility, and speed of metabolic processes of filamentous fungi, as well as their favourable nutrient composition and naturally fibrous texture. The number of mycoprotein-related patents is expected to rise, from both small companies as well as multi-national organisations. But also inventions related to supplements, colours and aromas from fungal sources will further increase in the future. With the incredible versatility of filamentous fungi, we will continue to find novel application areas within the entire value chains of the food industries.
When looking at the pharma industry, there has been a clear decreasing trend among both academic and corporate organisations regarding antibiotics research. Novel antibiotic discovery has been stagnating for many years , and any newly created antibiotics are mere iterations of previous core concepts. The search for novel antibiotics is now considered a low-reward effort by research funding agencies. As for private players, the incentives for novel antibiotics research often do not match the effort required for development. Lack of interest comes not only from the high investment costs required, but also that, if discovered, novel antibiotics will only be prescribed as a last line of defence in order to prevent acquired resistance to these new drugs, generating rather low revenues for pharmaceutical companies. Instead, however, the recombinant production of pharmaceuticals in fungal production systems is steadily increasing, in particular with the rise of personalised medicine and antibody-focused treatments. With an efficient secretion system, and the ability to produce complex and glycosylated proteins and chemicals, fungi are well-suited as efficient production hosts, and genetic engineering tools will certainly make them even more efficient in the future.
The amount, as well as the types, of (bulk) chemicals produced by fungal fermentation will increase in the future, and IP will continually be generated even for traditional processes such as organic acid production. We see constant innovation with new products entering the market and enhanced microbes being used for improved production processes. The fermentation step to produce the chemicals is now in many cases a mature technology, and the main innovation lies in the bioengineering of the organisms.
Similar to chemicals, despite a long history of enzyme production with filamentous fungi, it is still an important topic of innovation today. Enzyme production has had a tremendous impact not only in technical industries, but also in healthcare and biochemical synthesis processes. The advancements of biotechnology in these fields pave the way towards lower production costs of enzymes, improved gene discovery methods and faster development of production hosts. The increased availability of optimised fungal enzyme production systems also increases their use in industries dealing with bulk and low value products. As a prime example, low enzyme production costs are a crucial part in making lignocellulose fermentation processes for biofuel and greener bulk chemical production (biorefineries) economically viable and competitive. Furthermore, with the accessibility of technologies for enzyme discovery and “bench-to-market” routines, we foresee the number of enzyme-related patents to steadily increase. This is expected to be populated mostly by large private players with access to high-throughput pipelines for enzyme discovery and testing.
The IP landscape in fungi-related environmental technology is also expected to grow in the near future as the need for efficient and benign waste(water) treatment becomes more and more crucial. Scarcity of water around the world will demand more advanced water and environmentally friendly treatment applications. Other important areas that demand solutions are more efficient resource use and protection of ecosystems from problematic eutrophication due to (over)use of fertilizers. Due to their versatile character filamentous fungi offer an excellent opportunity for solving these problems and can be regarded as crucial players in the circular economy . We expect that more integrated processes, where filamentous fungi play a part in adding value to resource streams that are seen as waste, will be seen in upcoming patents.
Future developments in the field of fungal cultivation methods are more difficult to predict. The creation of IP for new equipment and techniques for cultivating microbes could logically follow the trend of fermentation technology developments in general. However, with the development of breakthrough gene engineering techniques and increasingly permissive regulation when it comes to GMOs, biotechnology as a field is shifting from a traditional fermentation-technology focus to a more microbe-engineering focus, so it would not be surprising if IP creation in the field of cultivation equipment will be decreasing over time, while the amount of patents being filed related to metabolic and genetic engineering will increase.
Finally, in the field of fungal biomaterials, we expect an increase in IP generation over the next decade, as the need and desire for renewable and biodegradable materials, that replace petroleum-based products, increases. Fungal biomaterials will shape the future of material sciences, design, fashion, architecture and other material applications.
To summarise, the ability of filamentous fungi to produce a plethora of different compounds has been responsible for their past and continued industrial importance. The key trends that we identified regarding the patenting landscape in the last 5 years (2015–2020) are the use of filamentous fungi as a food source (mycoprotein) by a wider variety of players, the continued improvement of cultivation techniques mostly due to metabolic engineering and new genetic engineering techniques, and the use of filamentous fungi biomass as biodegradable alternatives to petroleum-based materials. Furthermore, the use of fungi in environmental technology is increasing, with China spearheading the inventions in this field, and filamentous fungi are also becoming an increasingly important part in pesticide formulation and agricultural practices. We will certainly see a further increase of IP being generated for filamentous fungi, since the need for green and sustainable technology in all areas of industry is increasing. With only a fraction of fungi characterised and still a lot to learn regarding their metabolism and production of secondary metabolites, the potential of these fascinating organisms has by far not yet reached its peak.
Most patents were searched and analysed by using Orbit Intelligence (v.1.9.8), a software provided by Questel. The patents were searched, not by individual record, but by invention-based families (FamPat). In addition, they were searched without a restriction on countries or regarding their legal status, hence patents that were lapsed, expired or revoked would also show up in the search. Initially a set of defined key words in the title or claims served as a basic set of search parameters. With or without a specifically set time limit focusing either on patents with a publication date from 2015-01-01 to 28-02-2020 or patents dating as far back as possible in the Orbit Intelligence database. Next, within these basic searches, we looked at specific technology domains as provided by the software based on International Patent Classification (IPC) and Cooperative Patent Classification (CPC) codes. In addition, a combination of the provided technical domains at IPC/CPC code was sometimes used to get a better understanding. As an example, to search within the field of food chemistry in relation to animal feed, IPC: A23K+ was used.
The standard script that was used for the searches was:
("FILAMENTOUS" "FUNGI" OR "FILAMENTOUS" "FUNGUS" OR "FILAMENTOUS" "FUNGAL" OR "FILAMENTARY" "FUNGUS" OR "FILAMENTARY" "FUNGI" OR "MYCOPROTEIN" "FUNGI" OR "MYCOLOGICAL" "FUNGI" OR "MYCOLOGICAL" "FUNGUS" OR "MYCOLOGICAL" "FUNGAL" OR "ASPERGILLUS NIGER" OR "ASPERGILLUS ORYZAE" OR "RHIZOPUS OLIGOSPORUS" OR "RHIZOPUS ORYZAE" OR "FUSARIUM VENENATUM" OR "MYCOPROTEIN" "FUNGUS" OR "MYCOPROTEIN" "FUNGAL" OR "FUNGI-BASED BIOMASS" OR "FUNGAL BIOMASS")/CLMS/TI.
The statistical analysis was performed by the Orbit Intelligence software, however additional rules were added (if necessary) to group assignees if they were from the same mother company (e.g. Danisco & Genencor are grouped with DuPont), or from the same company/institute but applied their patents with slightly different assignee names. While these search and analysis techniques were used as the basis for the paper, it does not include all relevant patents in this field. There are additional patents that do not comply with the search words used but do describe a filamentous fungi application. Hence, the paper discusses some patents that fall outside the search. It should also be mentioned that the patents in “basic” search were not filtered regarding their relevance nor were they validated, hence the search could still include patents that have the right ‘words’, but do not have anything to do with the usage of filamentous fungi. Furthermore, especially within the technical domain of pharmaceuticals patents, some feature inventions protecting against filamentous fungi instead of using them.
Availability of data and materials
Intellectual property rights
Trade-related aspects of intellectual property rights
Single cell protein
Titre, rate or yield
Genetically modified organism
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Hüttner, S., Johansson, A., Gonçalves Teixeira, P. et al. Recent advances in the intellectual property landscape of filamentous fungi. Fungal Biol Biotechnol 7, 16 (2020). https://doi.org/10.1186/s40694-020-00106-z
- Intellectual property
- Filamentous fungi