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SUBMITTED TO:
PROF. A. DIKSHIT
PROF. H . K. KEHRI
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 -
1) Primary metabolites.
2) secondary metabolites.
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 .
• 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
PRIMARY METABOLITES
Aspergillus niger is used in industrial microbiology for mass
production of citric acid. (primary metabolite).
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.
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
(Calvo et. al 2002).
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.
Categories of secondary metabolites
1) Mycotoxins
2) Antibiotics
3) Alkaloids
4) Amino acids
5) Steroids
6) Vitamins
Mycotoxins
 Mycotoxins refer to the toxic secondary metabolites.
 They 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
Crops getting infected are as follows :-
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
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.
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.
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.
 Ochratoxin A  Ochratoxin
B
 Ochratoxin
C
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
Citrinin producers
 Aspergillus niveus
 Aspergillus ochraceus
 Aspergillus oryzae
 Aspergillus terreus
 Monascus ruber
 Monascus purpureus
 Penicillium citrinum
 Penicillium camemberti
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
Selman
Waksman
ANTIBIOTICS CAN BE DIVIDED
ACCORDING TO THEIR BIOACTIVITY INTO
:-
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
ANTIBIOTICS:
 PENICILLIN
 CEPHALOSPORINS
 STREPTOMYCIN
 GRISEOFULVIN
 CYCLOSPPORIN
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.
Florey (pictured), Fleming and
Chain shared a Nobel Prize in
1945 for their work on penicillin.
MOULD OF FUNGUS,
Penicillium
Chemical structure of Penicillin G
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
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.
Streptomyci
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.
GRISEOFULVI
N
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
• 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.
Alkaloids
Alkaloids are a group of naturally occurring chemical
compounds which mostly contain nitrogen atoms.
Beside carbon and hydrogen molecules of alkaloids may
contain-
• Sulfur
• Rarely chlorine
• Bromine Or phosphorus
ALKALOIDS BEING COSIDERED HERE ARE:
• Ergotamine
• Oxaline
• Paramine
EGROTAMINE
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 .
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.
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.
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.
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
Vitamins are secondary metabolites
VITAMINS CULTURE
RIBOFLAVIN (B2) Ashbya gossypii
L-SORBOSE Gluconobacter oxidans
5-KETOGLUCONIC
ACID
Gluconobacter oxidans
VITAMIN B12 Propionibacterium
shermanii,
Streptomycin,
Amino acids are secondary
metabolites
AMINO ACID CULTURE
Tryptophan Claviceps purpurea,
Escherichia coli
Threonine Streptomyces
racemosus
Phenyl alanine Corynebacterium
glutamicus
QUESTIONS
1) What are secondary metabolites?
2) Name different categories of secondary metabolites?
3) What are mycotoxins?
4) Name kinds of vitamins under secondary metabolites?
5) Secondary metabolite are produced in which phase?
References
 Principles of Microbiology , by Ronald Atlas
 A text book of basic and applied microbiology , K R Aneja , Pranay
jain , raman aneja
 Web sources
Thank you
THANK
YOU

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secondary metabolites

  • 1. 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 - 1) Primary metabolites. 2) 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 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 (Calvo et. al 2002).
  • 8.
  • 9. 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.
  • 10. Categories of secondary metabolites 1) Mycotoxins 2) Antibiotics 3) Alkaloids 4) Amino acids 5) Steroids 6) Vitamins
  • 11. Mycotoxins  Mycotoxins refer to the toxic secondary metabolites.  They 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
  • 12. Crops getting infected are as follows :-
  • 13. 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
  • 14. 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.
  • 15. 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.
  • 16.
  • 17. 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.
  • 18.  Ochratoxin A  Ochratoxin B  Ochratoxin C
  • 19. 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
  • 20. Citrinin producers  Aspergillus niveus  Aspergillus ochraceus  Aspergillus oryzae  Aspergillus terreus  Monascus ruber  Monascus purpureus  Penicillium citrinum  Penicillium camemberti
  • 21. 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 Selman Waksman
  • 22. ANTIBIOTICS CAN BE DIVIDED ACCORDING TO THEIR BIOACTIVITY INTO :-
  • 23. 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
  • 24. ANTIBIOTICS:  PENICILLIN  CEPHALOSPORINS  STREPTOMYCIN  GRISEOFULVIN  CYCLOSPPORIN
  • 25. 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.
  • 26. Florey (pictured), Fleming and Chain shared a Nobel Prize in 1945 for their work on penicillin. MOULD OF FUNGUS, Penicillium
  • 27. Chemical structure of Penicillin G
  • 28. 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
  • 29. 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. Streptomyci
  • 30. 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. GRISEOFULVI N
  • 31. 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
  • 32. • 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.
  • 33. Alkaloids Alkaloids are a group of naturally occurring chemical compounds which mostly contain nitrogen atoms. Beside carbon and hydrogen molecules of alkaloids may contain- • Sulfur • Rarely chlorine • Bromine Or phosphorus
  • 34. ALKALOIDS BEING COSIDERED HERE ARE: • Ergotamine • Oxaline • Paramine EGROTAMINE
  • 35. 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 .
  • 36. 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.
  • 37. 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.
  • 38. 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.
  • 39. 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
  • 40. Vitamins are secondary metabolites VITAMINS CULTURE RIBOFLAVIN (B2) Ashbya gossypii L-SORBOSE Gluconobacter oxidans 5-KETOGLUCONIC ACID Gluconobacter oxidans VITAMIN B12 Propionibacterium shermanii, Streptomycin,
  • 41. Amino acids are secondary metabolites AMINO ACID CULTURE Tryptophan Claviceps purpurea, Escherichia coli Threonine Streptomyces racemosus Phenyl alanine Corynebacterium glutamicus
  • 42. QUESTIONS 1) What are secondary metabolites? 2) Name different categories of secondary metabolites? 3) What are mycotoxins? 4) Name kinds of vitamins under secondary metabolites? 5) Secondary metabolite are produced in which phase?
  • 43. References  Principles of Microbiology , by Ronald Atlas  A text book of basic and applied microbiology , K R Aneja , Pranay jain , raman aneja  Web sources