''Rhizomucor pusillus'' is a

thermophilic A thermophile is a type of extremophile that thrives at relatively high temperatures, between . Many thermophiles are archaea, though some of them are bacteria and fungi. Thermophilic eubacteria are suggested to have been among the earliest bact ...

filamentous The word filament, which is descended from Latin ''filum'' meaning "Thread (yarn), thread", is used in English for a variety of thread-like structures, including: Astronomy * Galaxy filament, the largest known cosmic structures in the universe * ...

fungus A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

belonging to the family Lichtheimiaceae, within the order

Mucorales The Mucorales is the largest and best-studied order of zygomycete fungi. Members of this order are sometimes called pin molds. The term mucormycosis is now preferred for infections caused by molds belonging to the order Mucorales. Systematic ...

. It is known for its role in various industrial applications, particularly in

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

production and

food fermentation In food processing, fermentation is the conversion of carbohydrates to alcohol or organic acids using microorganisms—yeasts or bacteria—without an oxidizing agent being used in the reaction. Fermentation usually implies that the action of mi ...

, and has been studied for its safety and potential use in human consumption.

Diversity and ecology

''Rhizomucor pusillus'' belongs to the order

and the class

Mucoromycetes The Mucorales is the largest and best-studied order of zygomycete fungi. Members of this order are sometimes called pin molds. The term mucormycosis is now preferred for infections caused by molds belonging to the order Mucorales. Systematics ...

. ''R. pusillus'' is a member of the phylum

Mucoromycota Mucoromycotina is a subphylum of uncertain placement in Fungi. It was considered part of the phylum Zygomycota, but recent phylogenetic studies have shown that it was polyphyletic and thus split into several groups, it is now thought to be a para ...

(previously Zygomycota), which includes ''

Rhizopus microsporus ''Rhizopus microsporus '' is a fungal plant pathogen infecting maize, sunflower, and rice. A domesticated variant of this species is used in the preparation of traditional soy fermentation such as tempeh and sufu (see ''Rhizopus oligosporus''). ...

'', '' R. oligosporus'', and '' R. oryzae'', fungi that have been used for centuries to produce

tempeh Tempe or tempeh (; , ) is a traditional Indonesian food made from fermented soybeans. It is made by a natural culturing and controlled fermentation process that binds soybeans into a cake form. A fungus, '' Rhizopus oligosporus'' or '' Rhizopu ...

from the

fermentation Fermentation is a type of anaerobic metabolism which harnesses the redox potential of the reactants to make adenosine triphosphate (ATP) and organic end products. Organic molecules, such as glucose or other sugars, are catabolized and reduce ...

soybeans The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean. Soy is a staple crop, the world's most grown legume, and an important animal feed. Soy is a key source of f ...

. The Mucorales order belongs to the early diverging ancient fungi and is characterized by rapidly growing

mycelium Mycelium (: mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Its normal form is that of branched, slender, entangled, anastomosing, hyaline threads. Fungal colonies composed of mycelium are fo ...

and amorph structures formed in large quantities. The ''Rhizomucor'' genus can be recognized by a morphology intermediate between ''Rhizopus'' and ''Mucor''. ''R. pusillus'' is a filamentous fungus that is known as a pioneer species in compost, quickly utilizing easily accessible substrates. Currently, around 10 different '' Rhizomucor'' species are known, among which ''R. pusillus'', ''R. miehei'', and ''R. variabilis''. ''R. pusillus'' can grow at temperatures between 40-70 °C and is known for its thermostable enzyme production. ''R. pusillus'' is predominantly found in geothermal places that create and produce heat, such as compost piles, garbage, or landfills.

Applications in food industry

Fermentation has a long history of use in the

preservation Preservation may refer to: Heritage and conservation * Preservation (library and archival science), activities aimed at prolonging the life of a record while making as few changes as possible * ''Preservation'' (magazine), published by the Nat ...

and production of foods like

soy sauce Soy sauce (sometimes called soya sauce in British English) is a liquid condiment of China, Chinese origin, traditionally made from a fermentation (food), fermented paste of soybeans, roasted cereal, grain, brine, and ''Aspergillus oryzae'' or ''A ...

yogurt Yogurt (; , from , ; also spelled yoghurt, yogourt or yoghourt) is a food produced by bacterial Fermentation (food), fermentation of milk. Fermentation of sugars in the milk by these bacteria produces lactic acid, which acts on milk protein to ...

, and

alcoholic beverages Drinks containing alcohol are typically divided into three classes—beers, wines, and spirits—with alcohol content typically between 3% and 50%. Drinks with less than 0.5% are sometimes considered non-alcoholic. Many societies have a di ...

. With the current advances in technology, the cultivation of fungi, in the form of fungal biomass, can be used to produce

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

- and

fiber Fiber (spelled fibre in British English; from ) is a natural or artificial substance that is significantly longer than it is wide. Fibers are often used in the manufacture of other materials. The strongest engineering materials often inco ...

-rich ingredients for human consumption. A well-known example of fungal biomass is

Quorn Quorn is a brand of meat substitute products. Quorn originated in the UK and is sold primarily in Europe, but is available in 11 countries. The brand is owned by parent company Monde Nissin. Quorn is sold as both a cooking ingredient and as ...

(produced via fermentation of ''

Fusarium venenatum ''Fusarium venenatum'' is a microfungus of the genus ''Fusarium'' that has a high protein content. One of its strains is used commercially for the production of the single cell protein mycoprotein Quorn. ''Fusarium venenatum'' was discove ...

''), which has been on the international market for decades as a meat replacer. ''Rhizomucor'' species have also emerged as a promising source for food applications. Both ''R. pusillus'' and ''R. miehei'' are reported to be used to produce milk-clotting enzymes for cheese manufacturing. Primarily ''R. miehei'' has been used for enzyme preparations by industrial biotechnology companies, such as

Novozymes Novozymes A/S was a global biotechnology company headquartered in Bagsværd, outside of Copenhagen, Denmark. The company's focus was the research, development and production of industrial enzymes, microorganisms, and biopharmaceutical ingredie ...

, in food. Furthermore, ''Rhizomucor'' species have been isolated from different starter cultures of typical Asian fermented food products.

Safety

Toxicological evaluation

Studies have demonstrated that ''R. pusillus'' can be safely used to produce a novel

mycoprotein Mycoprotein (lit. "protein from fungus"), also known as mycelium-based protein or fungal protein, is a form of single-cell protein derived from fungi for human consumption. Though these products derived from mycoprotein often are referred t ...

through fermentation. ''R. pusillus'' used for the production of this mycoprotein cannot produce

mycotoxins A mycotoxin (from the Greek μύκης , "fungus" and τοξικός , "poisonous") is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually r ...

which are toxins produced by certain moulds (fungi) that can cause adverse health effects. The

whole genome sequence Whole genome sequencing (WGS), also known as full genome sequencing or just genome sequencing, is the process of determining the entirety of the DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's ...

of this strain was annotated and no genetic elements were found that share significant sequence homology with protein toxins, including the absence of mucoricin, an essential toxin in the pathogenesis of

mucormycosis Mucormycosis, also known as black fungus, is a severe fungal infection that comes under fulminant fungal sinusitis, usually in people who are immunocompromised. It is curable only when diagnosed early. Symptoms depend on where in the body the ...

. For foods containing novel proteins, potential

allergenicity An allergen is an otherwise harmless substance that triggers an allergic reaction in sensitive individuals by stimulating an immune response. In technical terms, an allergen is an antigen that is capable of stimulating a type-I hypersensitivit ...

of the proteins is a key safety consideration. One such product is a fungal biomass obtained from the fermentation of ''Rhizomucor pusillus''. Scaife et al (2024) concluded that based on in silico analyses and a literature review, the risk of allergenic

cross-reactivity Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test or assay, including diagnostic tests in medicine, and can be a c ...

of ''R. pusillus'' is low.

Regulatory approval

A ''R. pusillus'' strain has obtained regulatory approvals for food use, including self-affirmed

GRAS Gras may refer to: People * Basile Gras (1836–1901), French firearm designer * Enrico Gras (1919–1981), Italian filmmaker * Felix Gras (1844–1901), Provençal poet and novelist * Laurent Gras (disambiguation) * N. S. B. Gras (1884–1956), ...

(Generally Recognized as Safe) status in the United States and

novel food A novel food is a type of food that does not have a significant history of consumption or is produced by a method that has not previously been used for food. Designer food Designer food is a type of novel food that has not existed on any regional ...

approval in Singapore.

Roles in disease

Mucorales fungi, especially ''

Mucor ''Mucor'' is a microbial genus of approximately 40 species of molds and dimorphic fungi in the family Mucoraceae. The genus includes both pathogenic and avirulent species, and some members of it can be utilized in biotechnical applications. ...

'' species, can lead to serious but rare fungal infections in humans, called

. Mucormycosis is most commonly caused by ''

Rhizopus ''Rhizopus'' is a genus of common saprophytic fungi on plants and specialized parasites on animals. They are found in a wide variety of organic substances, including "mature fruits and vegetables", jellies, syrups, leather, bread, peanuts, and t ...

'' or ''

'' species, affects the sinuses or the lungs and causes symptoms like

cough A cough is a sudden expulsion of air through the large breathing passages which can help clear them of fluids, irritants, foreign particles and Microorganism, microbes. As a protective reflex, coughing can be repetitive with the cough reflex fol ...

nasal congestion Nasal congestion is the partial or complete blockage of nasal passages, leading to impaired nasal breathing, usually due to membranes lining the nose becoming swollen from inflammation of blood vessels. Background In about 85% of cases, nasal ...

, and

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

. Although mucormycosis can be fatal, it occurs primarily in patients who are severely

immunocompromised Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affe ...

or with severe

metabolic diseases A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the ...

. Mucorales do most frequently enter the body via the

respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respirato ...

, through inhalation of

spore In biology, a spore is a unit of sexual reproduction, sexual (in fungi) or asexual reproduction that may be adapted for biological dispersal, dispersal and for survival, often for extended periods of time, in unfavourable conditions. Spores fo ...

s. Spores may also enter the body through the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

or directly through the

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

in case of

trauma Trauma most often refers to: *Psychological trauma, in psychology and psychiatric medicine, refers to severe mental and emotional injury caused by distressing events *Traumatic injury, sudden physical injury caused by an external force, which doe ...

wound A wound is any disruption of or damage to living tissue, such as skin, mucous membranes, or organs. Wounds can either be the sudden result of direct trauma (mechanical, thermal, chemical), or can develop slowly over time due to underlying diseas ...

catheter In medicine, a catheter ( ) is a thin tubing (material), tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. ...

s, and contaminated surgical devices.

Infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s with Mucorales have remained extremely rare compared to their abundance in our daily life. Fungal spores are ubiquitous in the air and are inhaled regularly. It is highly improbable that healthy individuals are infected upon ingestion of fungi since the invasion occurs mainly through inhalation of spores, which can then

germinate Germination is the process by which an organism grows from a seed or spore. The term is applied to the sprouting of a seedling from a seed of an flowering plant, angiosperm or gymnosperm, the growth of a sporeling from a spore, such as the sp ...

and grow in the

host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County * Host Island, in the Wilhelm Archipelago, Antarctica People * ...

. There is no evidence of mucormycosis caused by

ingestion Ingestion is the consumption of a substance by an organism. In animals, it normally is accomplished by taking in a substance through the mouth into the gastrointestinal tract, such as through eating or drinking. In single-celled organisms, inge ...

of mycelium from fungi or foods containing fungi, as they are most often heat-inactivated, which kills

vegetative cells Vegetative describes vegetation. Vegetative may also refer to: *Vegetative reproduction, a type of asexual reproduction for plants *Persistent vegetative state, a condition of people with severe brain damage *Plant community A plant community is ...

and spores. Additionally, ''Rhizomucor'' species have been shown to cause less than 5% of mucormycoses cases. Mucoricin, an essential toxin in the pathogenesis of mucormycosis, is absent in ''R. pusillus''.

References

{{Taxonbar, from=Q7320764 Fungi Fungus species