LECTURE 8 Fungal Seconary Metabolites (Their relevance)

Question 1

The major groups of fungal SMs

Answer 1

• Polyketides (PKS)
• Nonribosomal peptides (NRPs)
• Terpenes
• Alkaloid

Question 2

Polyketide Biosynthesis

Answer 2

• Multi-domain proteins involved in polyketide biosynthesis.
• Related to eukaryotic fatty acid synthases.

Question 3

Polyketide Synthase Domains

Answer 3

• Ketoacyl CoA synthase (KS)
• Acyltransferase (AT) domain
• Acyl carrier protein (ACP)
• dehydratase (DH) domain.
• ketoreductase (KR) domain
• CYC, cyclase
• (TE) thioesterase.
• ER (Enoyl Reductase): Leads to the formation of unsaturated intermediates.
• MT (Methyltransferase): for thioester methylation.

Question 4

When were Aflatoxins discovered

Answer 4

early 1960s

Question 5

Aflatoxin name and production

Answer 5

• Named after Aspergillus flavus.
• Produced not only by Aspergillus flavus but also by other species.

Question 6

Health Impact of Aflatoxin

Answer 6

• Aflatoxicosis: Disease resulting from exposure to high levels of aflatoxin through ingestion or inhalation.
• Associated with sudden dog deaths due to Brazilian peanut meal and aflatoxin-contaminated maize outbreaks in Kenya.

Question 7

Aflatoxin Types

Answer 7

B1, B2, G1, G2

Question 8

Lovastatin role

Answer 8

Functions as a reducer for cholesterol and triglycerides.

Question 9

Lovastatin source

Answer 9

Isolated from Aspergillus
terreus

Question 10

LDL Cholesterol

Answer 10

Associated with atherosclerosis and coronary artery disease

Question 11

Lovastatin Cholesterol Impact

Answer 11

• Lovastatin is an inhibitor of HMG-CoA reductase in liver
• It reduces (bad cholesterol) LDL, and increases HDL (good cholesterol)

Question 12

Penicillin origin

Answer 12

Discovery by Mary Hunt, also known as “Mouldy Mary” in Illinois Peoria.

Question 13

Species Variability in Peniciilin

Answer 13

• Penicillium Species: More than 20 penicillin varieties identified in P. chrysogenum, surpassing P. notatum.
• Penicillin Varieties: Existence of more than one type of penicillin within the species.

Question 14

Penicillin Production

Answer 14

• P. notatum Surface Culture: Produces 2-pentenyl penicillin or Penicillin I.
• P. chrysogenum Cultivation: Yields benzylpenicillin or Penicillin II.

Question 15

Cyclosporine Composition

Answer 15

11 amino acid Cyclic NRP with D-
amino acid

Question 16

Cyclosporine in Medicine

Answer 16

• Immunosupressive agent
• Used in capsule and solution forms to prevent organ transplant rejection (e.g., liver, kidney, heart).
• Employed in managing autoimmune disorders like rheumatoid arthritis and psoriasis, particularly when steroids are ineffective.

Question 17

Cyclosporine production

Answer 17

Produced by Tolypocladium inflatum

Question 18

Mechanism of Action: Cyclosporine

Answer 18

T-Cell Inhibition: Influences T-cells within the immune system, reducing their activation by inhibiting the secretion of Interleukin-2.

Question 19

Gliotoxin name

Answer 19

Epipolythiodioxopiperazine

Question 20

Antibiotic & Immunosuppressive mycotoxin causes…

Answer 20

apoptosis in immune system cells

Question 21

Gilotoxin Fungal Producers:

Answer 21

Produced by various fungi, including human pathogens like Aspergillus fumigatus, Trichoderma, and Penicillium species.

Question 22

Gliotoxins contain what structural Element?

Answer 22

Essential Disulfide Bridge

Question 23

Gliotoxin toxicity mechanisms in host Cells.

Answer 23

• Direct inactivation of essential protein thiols
• Inhibits NADPH oxidase complex formation in neutrophils
• Production of Reactive oxygen species (ROS) formation, H2O2

Question 24

what cells in the immune system does gliotoxin target?

Answer 24

Macrophages, neutrophils, eosinophils

Question 25

α-Amanitin Structure and production

Answer 25

- Comprises a cyclic 8-amino acid peptide containing D-amino acids. - Produced by Amanita phalloides.

Question 26

α-Amanitin Toxicity

Answer 26

- Notably recognized as the most lethal mycotoxin, known as the Death Cap. - Distinct from other toxins due to its inner loop.

Question 27

α-Amanitin mechanism of Action

Answer 27

- Functions by inhibiting RNA polymerase II.

Question 28

α-Amanitin Health Impact

Answer 28

- Causes liver damage, kidney damage, organ failures, death 2- 7 days - Survivers suffer from liver damage

Question 29

Gibberellins Function

Answer 29

- Plant Hormones: Responsible for regulating plant development phases like germination, dormancy, and flowering. - Seed Dormancy Breakdown: Activate starch hydrolysis, facilitating seed dormancy breaking.

Question 30

Gibberellins Source

Answer 30

Initially isolated from Fusarium fujikuroi (formerly Gibberella fujikuroi).

Question 31

Biological Advantage:

Answer 31

Adaptation Role: Adaptation towards plant pathogenic or mutualistic lifestyle.

Question 32

Terpenes (Trichothecene)

Answer 32

* Mycotoxins, * Produced by Fusarium ssp. * Health hazard for animals and humans * They inhibit protein synthesis in ribosomes * Trichothecene mycotoxins can remain toxic for years in a normal environment. Ultraviolet light does not destroy trichothecenes and they are not soluble in water.

Question 33

Ergotamine

Answer 33

Tryptophan derived metabolites

Question 34

Ergotamine source

Answer 34

- Primarily associated with Claviceps purpurea. - infamous as a pathogen affecting rye, wheat, and various other crops.

Question 35

Ergotamine Pharmacological Effects:

Answer 35

- Neurotransmitter Similarity: Shares similarities with neurotransmitters such as serotonin and epinephrine. - Ingestion Impact: Ingestion leads to convulsions, vasoconstriction, and hallucinations.

Question 36

Ergotamine Medical Applications

Answer 36

- Historical Use: Initially employed to stop post-birth hemorrhages due to its vasoconstriction properties. However, it accelerates labor and encourages abortion. - Migraine Treatment: Due to its ability to narrow blood vessels in the brain, it's used in combating migraines. - CIA Use: Allegedly used by the CIA as a truth serum, possibly due to its psychological effects.

Question 37

Ergotamine) *