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Secondary Metabolism

Secondary metabolism

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Page 1: Secondary metabolism

Secondary Metabolism

Page 2: Secondary metabolism

Primary metabolism: known function

Example of primary metabolites: Pyruvate Ethanol Lactic acid

Primary metabolism is used for: Growth and development of hyphal structure Energy metabolism Regulation of metabolism Intermediate in biosynthesis of compound

Widely distributed in nature

Primary Metabolites

Page 3: Secondary metabolism

Often lack known function

Found in few species or genera

Specialised distribution peculiar to individual species or small groups of species: idiosynchratic- very unique, special and specific

Production of these compounds often after growth has stopped. Why?- limitation/nutrients depression- Contamination- competition- Fungal cell death due to physical and chemical factors

Secondary Metabolites

Page 4: Secondary metabolism

Primary metabolism Secondary metabolism

Function are known Function are usually unknown- lack

Widely distributed in nature Only found in few species or genera - idiosynchratic

Usually used for growth, energy and as intermediate

Produced usually after growth has stopped

Examples: Pyruvate, lactic acid, ethanol

Examples: Penicillin, cephalosporin, gibberellin,

lovastatin

Differences between primary metabolism and secondary metabolism

Page 5: Secondary metabolism

Common metabolites generated from secondary biosynthesis pathways in fungi

Page 6: Secondary metabolism

Some fungi accumulate primary metabolites

Citric acidFumaric acidEthanolLactic acid

Page 7: Secondary metabolism

What are the reasons for interest in secondary metabolites?

industries: i. Antibiotic: Penicillin and cephalosporinii. Itaconic acid: textile industriesiii. Gibberellin: plant growth regulatoriv. Animal feed

Pigment Bioluminiscences

Page 8: Secondary metabolism

Mycotoxin Aflatoxin: attack crops and cereals, by Fusarium. Zearalenone: attack animals (poultry and swine)-

cause infertility and abortion. Can be absorbed by human skin.

Phytotoxin and plant growth regulators produced by pathogenic fungi HC toxin: attack Zeamays (maize), from

Cochliobolus carbonum, it is a host specific toxin Amatoxin: by Amanita phalloides- A subgroup toxin Gibberellin and cytokinins: plant growth regulators

Toxic Metabolites by Fungi

Page 9: Secondary metabolism

Classified based on 5 main metabolic sources:

1. Amino acid2. Shikimic acid pathway for biosynthesis of aromatic

amino acid3. Polyketide biosynthetic pathway from Acetyl CoA4. Mevalonic pathway from Acetyl CoA5. Polysaccharides and peptidopolysaccharides

*3 and 4- most involved in production of secondary metabolites

*amino acid- biosynthetic origins in gycolysis and TCA cycle

Biosynthesis of secondary metabolites

Page 10: Secondary metabolism

Many Ascomycetes and several bacteria (e.g., Streptomyces) make the β-lactam antibiotic, Penicillin and Cephalosporin.

Penicillium chrysogenum, Aspergillus nidulans, Acremonium chrysogenum

The precursor substrates for biosynthesis β-lactam are amino acids

- Show the clear interaction of secondary with primary metabolites.

β-Lactam antibiotic

Page 11: Secondary metabolism

Penicillins and cephalopsorins share the initial steps of their biosynthesis, beginning with Val, Cys and α-aminoadipic acid.

These amino acids have their origins in the TCA

Naturally occurring penicillins produced in the absences of the side chain precursor supplement in the medium all contain fatty acid side chains

Peniciilin F, Penicillin K –derivatives of penicillin with different side chains

Page 12: Secondary metabolism

The evolutionary origin of secondary metabolic pathway comes from sequence comparisons of the cloned genes

The genes cloned from Penicillin chrysogenum, Aspergillus nidulans, Acremonium chrysogenum

Revealed in comparison with the analogous genes from the prokaryotes Streptomyces lipmanii and S. clavuligerus, striking similarity in both the nucleic acid and amino acid sequences.

Page 13: Secondary metabolism

Common evolutionary origin and cross kingdom transfer of the genes may have occurred about 370 mil years ago

P. chrysogenum produces 17 secondary metabolites

PATULIN- polyketide-related antibiotic produced by P. Urticae also known as P. Patulum and P. griseofulvum

Biosynthesised by acetate malonate pathway

Page 14: Secondary metabolism

Aspergillus flavus and A. parasiticus

Carcinogenic properties

Belong to the polyketide family of secondary metabolites derived from Acetyl CoA

Aflatoxin

Aspergillus flavus- stained by lactophenol blue