secondary metabolites

Secondary Metabolism is a term for pathways for small molecule and products of metabolism that are not absolutely required for the survival of the organism.
A secondary metabolite has an important ecological function.
Examples include antibiotics, mycotoxins etc.

1. SUBMITTED BY : SHADMA AFZAL MSc. III Semester SECONDARY METABOLITES SUBMITTED TO: PROF. A. DIKSHIT PROF. H . K. KEHRI

2. What are metabolites? Metabolites are the intermediates and products of metabolism, are typically characterized by small molecules with various functions. Metabolites can be categorized into - Primary metabolites. secondary metabolites.

3. Primary Metabolism Primary Metabolism encompasses reactions involving those compounds which are formed as a part of normal anabolic and catabolic processes. Anabolism is the set of metabolic pathways that construct molecules from smaller unit. Catabolism where large molecules are broken down into smaller parts .

4. primary metabolites are involved in maintaining normal physiological processes thus, it is often referred to as a central metabolite. Essential for proper growth, development, and reproduction. Examples include alcohols such as ethanol, lactic acid, and certain amino acids. PRIMARY METABOLITES

5. Aspergillus niger is used in industrial microbiology for mass production of citric acid . (primary metabolite).

6. Secondary Metabolism Secondary Metabolism is a term for pathways for small molecule and products of metabolism that are not absolutely required for the survival of the organism . A secondary metabolite has an important ecological function. Examples include antibiotics, mycotoxins etc.

7. SECONDARY METABOLITES Because they are synthesized late in growth cycle in stationary phase ( idiophase ). Why secondary metabolites are of no use to the organism ? Secondary metabolites are structurally diverse low molecular mass molecules that are not essential for the growth and survival of the producing organisms. Secondary metabolite serve to increase the fitness of the producing organisms and to decrease the fitness of surrounding organisms. Metabolites play a role in initiation, regulation and process of sporulation ( C alvo et. al 2002).

8. Special features Secondary metabolites are known from the ancient times. The first crystalline fungal product from Penicillium flaucoma considered as microbial secondary metabolites was mycophenolic acid discovered in 1896 by Gosio . The secondary metabolites isolated from microbes and exhibits either antimicrobial(antibacterial, antifungal, antiprotozoal), antitumor and antiviral activities used to be called as antibiotics.

9. Categories of secondary metabolites Mycotoxins Antibiotics Alkaloids Amino acids Steroids Vitamins

10. Mycotoxins Mycotoxins refer to the toxic secondary metabolites. T hey are neither necessary for growth nor the development of the fungi. Some of these very severe effects on animal, plant and microbial system (fungal food poisoning- mycointoxication ). Mycotoxins are poisons produced by naturally occurring moulds growing on plant material. Symptoms of a mycotoxicosis depend on: The type of mycotoxin ; The concentration; As well as age Health And sex of the exposed individual

11. Crops getting infected are as follows :-

12. Mycotoxins present in different commodities and associated mycotoxins - Mycotoxins mycotoxicoses commodities Aspergillus toxins- Aflatoxins , B1,B2, Liver cancer CORN , PEANUTS G1, G2 Sterigmatocystin carcinogenesis green coffee Ochratoxins renal tumour corn coffee , Fusarium toxins monoliformin onlyai disease rice Fumornisins promote cancer corn Trichothecenes dermatitis corn, wheat Zearelenone cervical cancer corn meal Penicillium toxins Citroviridin cardiac damage mouldy , peanut Patulin capillary damage in vital organs cedar , apple

13. MODE OF MECHANISM Mycotoxins have the potential for both acute and chronic health effects via ingestion, skin contact, and inhalation. These toxins can enter the blood stream and lymphatic system. They inhibit protein synthesis, damage macrophage systems and inhibit particle clearance of the lung.

14. 1. AFLATOXINS   Naturally occurring mycotoxins that are produced by many species of Aspergillus , aflatoxinsB2a, aflatoxicol , aflatoxinsP1 are some species of aflatoxins . Aspergillus flavus and Aspergillus parasiticus are among the most carcinogenic substance producing species, disease like ergotism , alimentary toxic aluki (ATA) and the liver cancer or Reye’s syndromes caused by aflatoxins . Children are particularly affected by aflatoxin exposure which leads to stunted growth and delayed development. In Kenya in 2004, maize contaminated with Aflatoxins B1 caused liver disease and jaundice in 317 people, 125 people died.

15. 2. OCHRATOXIN Produced by  Penicillium   and  Aspergillus  sp.   Aspergillus carbonarius   is the main species found on vine fruit, which releases its toxin during the juice making process. Aspergillus ochraceus  is found as a contaminant  of a wide range of commodities  beverages.

16. Ochratoxin A Ochratoxin B Ochratoxin C

17. 3. Citrinin   Citrinin is a mycotoxin originally isolated from Penicillium citrinum . Citrinin is associated with yellow rice disease in Japan and acts as a  nephrotoxin ( excretory system). Citrinin

18. Citrinin producers Aspergillus niveus Aspergillus ochraceus Aspergillus oryzae Aspergillus terreus Monascus ruber Monascus purpureus Penicillium citrinum Penicillium camemberti

19. Antibiotics The term ‘antibiotic’ was coined by Selman Waksman in 1942. The secondary metabolites isolated from microbes and exhibits either antimicrobial(antibacterial, antifungal, antiprotozoal ), antitumor and antiviral activities used to be called as antibiotics. It is used to treat infections caused by microorganisms, including fungi and protozoa. Selman Waksman

20. ANTIBIOTICS CAN BE DIVIDED ACCORDING TO THEIR BIOACTIVITY INTO :-

21. ANTIBIOTICS PRODUCING MICROORGANISM BACTERIAL ORIGIN AMPHOTERICIN B Streptomyces nodosus BACITRACIN Bacillus subtilis CHLORAMPHENICOL Streptomyces venezuelae ERYTHROMYCIN Streptomyces erythreus KANAMYCIN Streptomyces kanamyceticus NEOMYCIN Streptomyces fradiae NOVOBIOCIN Streptomyces niveus FUMAGILLIN Aspergillus fumigatus AMPICILLIN Penicillium CEPHALOSPORIN cephalosporium FUNGAL ORIGIN

22. ANTIBIOTICS : PENICILLIN CEPHALOSPORINS STREPTOMYCIN GRISEOFULVIN CYCLOSPPORIN

23. 1. PENICILLIN Penicillin is a secondary metabolite or idiolite ; not required for growth of fungus. Production of fungal biomass occurs in growth phase called trophophase . Accumulation of penicillin occurs in idiophase . Its production only begins after near exhaustion of carbon source. High levels of glucose repress penicillin production.

24. Florey (pictured), Fleming and Chain shared a Nobel Prize in 1945 for their work on penicillin. MOULD OF FUNGUS, Penicillium

25. Chemical structure of Penicillin G

26. 2. CEPHALOSPORINS Cephalosporin are a group of broad spectrum ,semi- synthetic beta –lactam antibiotics derived from the mould Cephalosporium acremonium . They are divided into three groups-cephalosporin N and C are chemically related to penicillins and cephalosporin P a steroid antibiotic.

27. 3. STREPTOMYCIN Discovered by Selman Waksman. Streptomycin is a secondary metabolite produced by Streptomyces griseus an actinobacterium . Used in treatment of diseases; infective endocarditis, tuberculosis, tularemia , in veterinary medicine for use against gram negative bacteria in large animals. Streptomycin

28. 4. Griseofulvin   Griseofulvin also known as Grisovin is an antifungal drug that is administered orally. It is derived from the mould Penicillium griseofulvum and streptomyces griseus . It is used both in animals and in humans, to treat fungal infections of the skin and nails.   GRISEOFULVIN

29. STEROIDS A steroid is an organic compound with four rings arranged in a specific configuration. Use of micro-organisms to carry out biotransformations of steroids is important. To relieve pain , associated with rheumatoid arthritis. Steroid hormones regulate human sexuality & human reproductive cycles. Oral contraceptives

30. Rhizopus arrhizus :- hydrolytes progesterone forming another steroid with introduction of oxygen. Cunnighamella blakesleeana :- can hydroxylate steroid cortexolome to form hydrocortisone. Rhizopus nigricans :- Numerous similar transformations are carried out to produce various steroid derivatives for medicinal uses.

31. Alkaloids   Alkaloids are a group of naturally occurring chemical compounds which mostly contain nitrogen atoms. Beside carbon and hydrogen molecules of alkaloids may contain- S ulfur R arely chlorine Bromine Or phosphorus 

32. ALKALOIDS BEING COSIDERED HERE ARE: Ergotamine Oxaline Paramine EGROTAMINE

33. 1. Ergotamine It was first discovered by Arthur Stoll at Sandoz in 1918 and marketed as Gynergen in 1921. Possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor. Ergotamine is a secondary metabolite, the principal alkaloid produced by the ergot fungus, Claviceps purpurea , and related fungi in the family Clavicipitaceae .

34. Mechanism of action The mechanism of action of ergotamine is complex. The molecule shares structural similarity with neurotransmitters such as Serotonin dopamine epinephrine, thus bind to several receptors. 

35. ERGOT-DERIVED DRUG It can increase uterine contractivity therapeutically immediately post-partum to decrease uterine bleeding. Ergotamine continues to be prescribed for migraines. Its medicinal usage began in the 16th century to induce childbirth.

36. 2. Oxaline Derived from Penicillium oxalicum , which usually grows on dead and decaying matter . This alkaloid was found to arrest the cell cycle by inhibition of tubulin polymerisation .

37. 3 . Paramine Produced by some grass infecting Neotyphodium species . The alkaloid protects the grass against grazing by mammals and insects . This alkaloid can also be used as bio-insecticide and bio-pesticide . grass infecting Neotyphodium species

38. Vitamins are secondary metabolites VITAMINS CULTURE RIBOFLAVIN (B2) Ashbya gossypii L-SORBOSE Gluconobacter oxidans 5-KETOGLUCONIC ACID Gluconobacter oxidans VITAMIN B12 Propionibacterium shermanii , Streptomycin, Aureomycin .

39. Amino acids are secondary metabolites AMINO ACID CULTURE Tryptophan Claviceps purpurea , Escherichia coli Threonine Streptomyces racemosus Phenyl alanine Corynebacterium glutamicus

40. QUESTIONS What are secondary metabolites? Name different categories of secondary metabolites? What are mycotoxins ? Name kinds of vitamins under secondary metabolites? Secondary metabolite are produced in which phase?

41. R eferences Principles of Microbiology , by Ronald Atlas A text book of basic and applied microbiology , K R Aneja , Pranay jain , raman aneja Web sources

42. Thank you THANK YOU