Primary & secondary metabolites of fungi

The metabolism is defined as the sum of all the biochemical reactions carried out by an organism.

Primary metabolites Are those that are essential for growth to occur. Associated with rapid initial growth phase of the organism. proteins carbohydrates nucleic acids lipids

Examples on primary metabolites produced in abundance include Enzymes, fats, alcohol and organic acid.

Secondary metabolites Compounds produced by an organism that are not required for primary metabolic processes and not used for growth. It is used for survival or nutrition storage.

Produced when organism enter the stationary phase. Secondary metabolites are produced when the cell is not operating under optimum conditions e.g. when primary nutrient source is depleted.

Metabolites produced in this phase are often associated with differentiation and sporulation and have biological activities.

Some examples of fungal secondary metabolites and its usage Penicillin (Penicillium chrysogenum) Antibiotics Cyclosporin (Trichoderma) Immunosuppressant Growth promoter Zearalonone (Gibberella zeae) Agriculture Amylase (Aspergillus niger) Enzymes Ancaflavin (Monascus purpureus) Pigments

similarities between the pathways that produce primary and secondary metabolites 1- The product of one reaction is the substrate for the next and the first reaction in each case is the rate-limiting step. 2- Also the regulation of secondary metabolic pathways is interrelated in complex ways to primary metabolic regulation.

Clear reasons exist for studying secondary metabolites Many have been found to have use in industry and medicine. Six of the twenty most commonly prescribed medications for humans are of fungal origin. Some metabolites are toxic to humans and other animals.

biosynthetic pathways 1-polyketides pathway 2- mevalonate pathway 3- amino acids pathway

* In addition, genes for the synthesis of some important secondary metabolites are found clustered together, and expression of the cluster appears to be induced by one or a few global regulators. * Some of the 'global regulators' are also involved with sporulation and hyphal elongation.

Polyketide Metabolites Acetate ح polymerizationح polyketide processing Staggering no. Of possible structure built from the simple primer unit Cyclisation, lactonisation, formation of amides

polyketide secondary metabolites tetrahydroxynaphthalene orsellinic acid -Sterigmato cyctin polyketide secondary metabolites fumonisin statins aflatoxins

Aflotoxins are produced in members of the Aspergillus parasiticus group via the polyketide Aflatoxin B1 is one of the most toxic compounds known.

The structure of Alphatoxin B1

- At lower levels and following prolonged exposure, the toxins cause liver cancer in humans. - Animals tend to avoid contaminated feed, but as B1 is so highly toxic, even large animals can be killed by small, almost undetectable quantities.

Patulin antibiotic synthesized on an acetate/malonate pathway. Its biosynthetic pathway is still unclear, but it appears that several alternate pathways may result in the same end product. Structure of Patulin

It is now also known to be a compound produced by Penicillium expansum in contaminated apples.

Aromatic Compounds Cyclic compounds can be synthesized via the polyketide pathway. Zearalenone is one interesting example from this group. The compound regulates perithecium formation in the fungus.

Structure of Zearalenone

penicillin & cephalosporin Amino Acid Pathway Antibiotics penicillin & cephalosporin defensin plectasin B lactams antibiotics Peptides act against bacteria

Toxins derived from amino acid synthesis psilocybin (Psilocybe) Bufotenine (Amanita). act on nerve impulses hallucinations The fungus Aminata

Plant Growth Regulators Many pathogenic and benign fungi produce auxin, cytokinins, gibberellins and abscisic acid. In fact the gibberlellins were first found in the fungus Gibberella fujikuroi, a pathogen that causes tall, straggly growth of rice.

The gibberellins are diterpenes produced by the mevalonate/isoprenoid pathway. The function of these compounds in fungi that colonise plants seem clear. Modification of host tissue enhances colonisation, releases nutrients for fungal metabolism and regulates host reproduction.

The function of plant growth regulation in fungi found outside plants is unclear. Some plant fungi appear to modify host production of growth regulators, resulting in alterations of host metabolism.

For instance, initiation of AM in roots results in a slowing of root tip elongation and increase in lateral formation.

The cause may be associated with a change in concentrations of auxins and/or cytokinins from the fungus or induced in the host, an increase in local concentration of phosphate due to the fungi, or a factor influenced by either. Increases in expression of plant hormones may be direct or indirect.

Toxins In general, toxins associated with fruiting bodies are important because consumption of the fruiting body can result in poisoning. Toxins associated with microfungi are important because they become evident after consumption of contaminated food.

In addition, toxins are produced from a myriad of pathways, and have enormously diverse effects. That they may be produced at a different point in the life cycle of a fungus is simply another aspect of the complex subject.

The function of toxins to fungi has been subject of much speculation The function of toxins to fungi has been subject of much speculation. Colonization (contamination) of organic materials is a prelude to the digestion of the material by the fungus. The production and expression of toxins is one mechanism the microbe has to protect the food, provided competitors detect the presence of the microbe and toxin.

The conditioned response to the fungus thus reduces the consumption of the fungal substrate. The “detection” molecule may be other than the toxin.

Objectionable flavors and smells may thus be warnings to competitors Objectionable flavors and smells may thus be warnings to competitors. Overall, the resultant reduction of feeding increases the chances of the fungi surviving

Thank You