Potential Application Of Fungi In IndustryApplied Mycology and PhycologySubject Code-MB104

Prepared and presented byDeepika RanaRoll No. 1601M.Sc. Microbiology1st SemesterMD University, Rohtak

•Fungi are prominent sources of pharmaceuticals and are used in many industrial fermentative processes, such as the production of enzymes, vitamins, pigments, lipids, glycolipids, polysaccharides and polyhydric alcohols.

•Fungi are extremely useful in making high value products like myco-proteins and acts as plant growth promoters and disease suppressor.

•Fungal secondary metabolites are important to our health and nutrition and have tremendous economic impact. In addition to this, fungi are extremely useful in carrying out biotransformation processes.

•Recombinant DNA technology, which includes yeasts and other fungi as hosts, has markedly increased market for microbial enzymes. 

Fungi in Industry•Fungi in enzyme production

•Major Vitamins from fungi•Organic acids from fungi•Fungi in medicine•Fungal metabolites of pharmaceutical importance•Fungi in beverage industry•Designing of vectors

•There are several multinational companies having stake in manufacturing industrial enzymes from fungi. Biocon India Ltd. is a major bulk enzyme producer in India.• Use of Enzymes for different purposes• Food 45 %• Detergent 34 %•Textile 11 %•Leather 3 %•Pulp/paper 1 %•Others 6 %

Fungi in enzyme production

THE MAJOR ENZYMES SOURCED FROM FUNGIENZYME SOURCE USES•Acid, alkaline & Aspergillus oryzae; A. niger Meat tenderization, Bakeryneutral proteases A. flavus; A. sojae •Cellulase Trichoderma koningi Paper industry, Detergent, Coffee•Diastase Aspergillus oryzae Acid reflux, Food Supplement•Glucoamylase Aspergillus niger; A. oryzae Sweeteners•Invertase Saccharomyces cerevisiae Sugar Candies •Lactase S. lactis; Rhizopus oryzae Lactose intolerant patients•Ligninase Phanerochaete chrysosporium Pulp and Paper industry•Lipase Rhizopus spp. Baking, Pancreatic disorders•Pectinase A. niger; Sclerotinia libertina Fruit juices

Major vitamins from fungiVitamin Fungus

producing Uses

Riboflavin (Vitamin B2)

Ashbya gossypiiCandida famata

Increasing energy levels; boosting immune system function; maintaining healthy hair, skin, mucous membranes, and nails; slowing aging

Panthothenic acid (Vitamin B5)

Fusarium oxysporum

Used orally for osteoarthritis, rheumatoid arthritis, Parkinson's disease, nerve pain, premenstrual syndrome (PMS), enlarged prostate,

NADH Candida boidinii

Treating high blood pressure, high cholesterol, depression, and Parkinson’s diseasereducing signs of aging; and protecting against the side effects of an AIDS drug called zidovudine (AZT)

S-adenosylmethionine(SAMe)

Sachharomyces saké

used for depression,   osteoarthritis, chronic lower back pain, Alzheimer's disease, slowing the aging process, attention deficit-hyperactivity disorder (ADHD),migraine, headache, and lead poisoning.

Glycolipid Mannosylerythritol lipids

Ustilago scitamineaNBRC 32730

Biosurfactant 11 Vitamins and Related Compounds: Microbial ProductionSAKAYU SHIMIZU, Kyoto, Japan

Other products of fungi•Mycoprotein is the protein from fungi. The main mycoprotein on sale in Europe and North America is called Quorn. It was originally developed as a food source to combat food shortages.•Quorn is the leading meat free brand within the UK and Ireland. All Quorn products contain mycoprotein which is derived from the fungus Fusarium venenatum.

•Pullulan is a polysaccharide produced by Aureobasidium pullulans and can be woven into fibers and has potential in the production and strengthening of fabrics. Special fishing lines and bulletproof vests are some of the products that contain these special polysaccharides. 

Aureobasidium pullulans

•Beta-glucans produced by certain yeast are being used for encapsulation of foods and medicines. They control the slow release of flavors and drugs.

•Chitin is second behind cellulose as the most abundant compound in nature. Commercially produced chitin in used in threads for suturing and as fillers in different foods.

Organic acids from fungiOrganic acid Source Uses

Citric acid Aspergillus niger In food preservation, powerful cleaning agent and in cosmetic products

Fumaric acid Rhizopus nigricans Used in food and beverage products, as oral pharmaceutical formations

Gluconic acid Aspergillus niger Acidity regulator as food additive, cleaning products

Itaconic acid A. terreus Prepare acrylic fibres and rubbers, reinforced glass fibre, in water treatment systems, artificial diamond and lens

Kojic acid A. oryzae Used in food and cosmetics as skin lightening agent, change colour of substances

Fungi in medicine•Fungi in antibiotics

Medicine Fungus involved Use

Penicillin Penicillium chrysogenum

Anti-bacterial(gram +ve)

Cephalosporin Cephalosporium Anti-bacterial(gram +ve)

Griseofulvin Penicillium griseofulvum

Fungi-static, treatment of dermatophytes

Lentinan Lentinus sp. Against Mycobacterium tuberculosis, Listeria sp. and Herpes Simplex Virus-I(HSV-1)

Schizophyllan Schizophyllum Antibacterial(against Staphylococcus aureus) and Antifungal(against Candida albicans)

•Mushrooms and polypores are rich source of natural antibiotics. The cell wall glucans are well known for their immunomodulatory properties, and the secondary metabolites are active against bacteria and viruses. Exudates from mushroom mycelia are active against protozoa such as the malarial parasite Plasmodium falciparum.

•Non-antibiotic Therapeutics from Fungi•There are non-antibiotic therapeutic agents obtained from fungi that have revolutionized medical practice. Cyclosporin is an important immunosuppressant drug that is used in organ transplantation surgery. Cyclosporin-A is derived from Tolypocladium inflatum, and Aspergillus sp. • About 20% of the drugs produced by pharmaceutical industry today are derived from fungi •Lovastatin is a cholesterol biosynthesis inhibitor derived from Aspergillus terreus. It is one of the many drugs used as a cholesterol reducing agent. A similar cholesterol reducing drug is produced from Penicillium citrinum, and it is called Pravastatin.

•Fungi are the source of vitamin B12 (Saccharomyces cerevisiae) and other vitamins (S. cerevisiae, Ashbya sp., Blakeslea sp.), hallucinogens (Psylocybe sp.), and steroids useful in fertility regulation (Rhizopus spp.).

Lovastatin

Griseofulvin

Cyclosporin

Lentinan

Penicillin

Pravastatin

Fungal metabolites•The metabolite named gibberelic acid, is used as a plant growth stimulator, produced by growing the fungus Giberella fujikuroi on solid substrates.•Gibberelic acid stimulates both cell division and cell elongation and hastens plant maturation and seed germination. It is applied to growing crops (field crops, small fruits, vines and fruit trees) ornamentals and shade trees, and ornamental plants, shrubs and vines.Claviceps purpurea The ergots contain many alkaloids. Their strongest effect is intoxication, caused by lysergic acid amides, one of which is the recreational (and illegal) drug, LSD. Ergot alkaloids have a number of medicinal uses. Perhaps the most widespread use is in the treatment of migraines. The vasodilator activity reduces tension during an attack. The drugs also reduce blood pressure, though with untoward side effects. Alkaloids are now produced in culture by strains of C. fusiformis and C. paspalii.

Giberella fujikuroi

In Beverage Industry•Distilled Alcohol:   Saccharomyces and Schizosaccharomyces•Industrial alcohol •Alcoholic beverages •Whiskey is made largely from barley.•Bourbon is a form of whiskey made from fermented corn.•Vodka is produced largely from potatoes in Russia and other east

European countries because they are cheap. •Rum is a distilled spirit made from sugar-containing substrates like molasses and cane juice. •Cognac is made from distilled grape wine to prevent spoilage in shipment. •Brandy is made in a similar way as cognac, initially from grape wine but later in North America from fermented juices of pears and peaches.•Tequila is a briny liquor made exclusively in Mexico from fermented juice of the Agavecactus.

Wine in the strict sense is the fermented juice of grapes. Wines are named after the type of grapes or the geographic area or specific village where they were first produced. For example,Burgandy, Bordeaux, Champagne, andAlsacs are important wines of France.  There are red, white, and pink (rosé) wines,  The common muscadine grape.Beer is a beverage obtained by the alcoholic fermentation by yeasts of a malted cereal, usually barley malt, with or without other starchy materials, and to which hops have been added .  There are two types of beers, lager and ales.  The yeast used in beer brewing isSaccharomyces cerevisiaeKanji: A beerlike beverage made with carrots and beets fermented with Hansenula. Taste much like cherry wine.Rice Beer: Rice beer is called sake in Japan, murcha or pachwai in India. It is made with rice plus species of Mucor or Aspergillus oryzea and sugar.

Yeast being added to the mash during beer making.

Designing of vectorsThe most important recent development in microbial biotechnology is the use of fungi as expression hosts for recombinant proteins used as therapeutic agents for human diseases. Yeasts have been the expression vectors for more than 500 mammalian proteins. Among eukaryotes, fungal cell cultures have the advantage that they are easy to grow and inexpensive to maintain.Production of Hepatitis-B Vaccine from Pichia pastorisPichia pastoris expression vector has been the classical example of how a fungal expression host can reduce the cost of a vaccine considerably. Earlier, a single dose of Hepatitis-B vaccine was costing about Rs. 800/- but now the cost has been reduced to Rs. 80/- per dose. This is because P. pastoris can be grown easily and economically in large bioreactors. Development of P. pastoris as a host organism for the production of heterologous proteins would provide a means of achieving high yields of fully active products.

Some important therapeutic recombinant proteins expressed in Pichia pastorisProtein Indication Firm •Angiostatin Anti-angiogenic EntreMed•Elastase Cystic fibrosis Dyax•Endostatin Anti-angiogenic EntreMed

•Epidermal Diabetes Transitiongrowth factor Therapeutics•Hepatitis-B Serum hepatitis Glaxo surface antigen -SmithKline•Human serum Stabilizing Mitsubishialbumin blood in Pharma burn/shock•Insulin-like Deficiency of Cephalongrowth factor-1 of the sameNote: Data from Tillmann U. Gerngross, Nature Biotechnology, 2004

BRAND NAME RECOM. PROTEIN COMPANY •Actrapid Insulin NovoNordisk • Ambrix Hepatitis-B GlaxoSmithKline surface antigen • Comvax …….”……. Merck • Elitex Urate oxidase Sanofi-Synthlabo • Glucagen Glucagon Novo Nordisk • HBVAXPRO Hepatitis-B Aventis Pharma Surface antigen • Leukine Granulocyte Berlex macrophage CSF • Regranex rh Platelet-derived Ortho-McNeil Growth factor & Janssen-Cilag

SOME THERAPEUTIC RECOMBINANT PROTEINS EXPRESSED BY SACCHAROMYCES CEREVISIAE

References NOVEL APPLICATIONS OF FUNGI. S. B. SULLIA. Emeritus

Professor, Department of Microbiology & Biotechnology. Bangalore University

Vitamins and Related Compounds: Microbial Production SAKAYU SHIMIZU, Kyoto, Japan

Production of glycolipids biosurfactants, Mannosylerythritol Lipids by a smut fungus Ustilago scitaminea NBRC 32730

Tomotake Morita, Yuko Ishibashi, Tokuma Fukuoka Biosc. Biotechnol. Biochem., 73 (3), 788-792, 2009

Production of food and beverage www.angelfire.com Mycology - Feeding - Secondary Metabolites

www.bugs.bio.usyd.edu.au Mycology - Uses of Fungi - Fungal Drugs

www.bugs.bio.usyd.edu.au LOVASTATIN TABLETS, Usp www.dailymed.nlm.nih.gov Google images

Thank you