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BI441 > LECTURE 8 Fungal Seconary Metabolites (Their relevance) > Flashcards

LECTURE 8 Fungal Seconary Metabolites (Their relevance) Flashcards

1
Q

The major groups of fungal SMs

A
  • Polyketides (PKS)
  • Nonribosomal peptides (NRPs)
  • Terpenes
  • Alkaloid
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2
Q

Polyketide Biosynthesis

A
  • Multi-domain proteins involved in polyketide biosynthesis.
  • Related to eukaryotic fatty acid synthases.
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3
Q

Polyketide Synthase Domains

A
  • 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.
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4
Q

When were Aflatoxins discovered

A

early 1960s

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5
Q

Aflatoxin name and production

A
  • Named after Aspergillus flavus.
  • Produced not only by Aspergillus flavus but also by other species.
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6
Q

Health Impact of Aflatoxin

A
  • 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.
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7
Q

Aflatoxin Types

A

B1, B2, G1, G2

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8
Q

Lovastatin role

A

Functions as a reducer for cholesterol and triglycerides.

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9
Q

Lovastatin source

A

Isolated from Aspergillus
terreus

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10
Q

LDL Cholesterol

A

Associated with atherosclerosis and coronary artery disease

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11
Q

Lovastatin Cholesterol Impact

A
  • Lovastatin is an inhibitor of HMG-CoA reductase in liver
  • It reduces (bad cholesterol) LDL, and increases HDL (good cholesterol)
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12
Q

Penicillin origin

A

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

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13
Q

Species Variability in Peniciilin

A
  • 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.
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14
Q

Penicillin Production

A
  • P. notatum Surface Culture: Produces 2-pentenyl penicillin or Penicillin I.
  • P. chrysogenum Cultivation: Yields benzylpenicillin or Penicillin II.
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15
Q

Cyclosporine Composition

A

11 amino acid Cyclic NRP with D-
amino acid

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16
Q

Cyclosporine in Medicine

A
  • 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.
17
Q

Cyclosporine production

A

Produced by Tolypocladium inflatum

18
Q

Mechanism of Action: Cyclosporine

A

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

19
Q

Gliotoxin name

A

Epipolythiodioxopiperazine

20
Q

Antibiotic & Immunosuppressive mycotoxin causes…

A

apoptosis in immune system cells

21
Q

Gilotoxin Fungal Producers:

A

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

22
Q

Gliotoxins contain what structural Element?

A

Essential Disulfide Bridge

23
Q

Gliotoxin toxicity mechanisms in host Cells.

A
  • Direct inactivation of essential protein thiols
  • Inhibits NADPH oxidase complex formation in neutrophils
  • Production of Reactive oxygen species (ROS) formation, H2O2
24
Q

what cells in the immune system does gliotoxin target?

A

Macrophages, neutrophils, eosinophils

25
Q

α-Amanitin Structure and production

A
  • Comprises a cyclic 8-amino acid peptide containing D-amino acids.
  • Produced by Amanita phalloides.
26
Q

α-Amanitin Toxicity

A
  • Notably recognized as the most lethal mycotoxin, known as the Death Cap.
  • Distinct from other toxins due to its inner loop.
27
Q

α-Amanitin mechanism of Action

A
  • Functions by inhibiting RNA polymerase II.
28
Q

α-Amanitin Health Impact

A
  • Causes liver damage, kidney damage, organ failures, death 2- 7 days
  • Survivers suffer from liver damage
29
Q

Gibberellins Function

A
  • Plant Hormones: Responsible for regulating plant development phases like germination, dormancy, and flowering.
  • Seed Dormancy Breakdown: Activate starch hydrolysis, facilitating seed dormancy breaking.
30
Q

Gibberellins Source

A

Initially isolated from Fusarium fujikuroi (formerly Gibberella fujikuroi).

31
Q

Biological Advantage:

A

Adaptation Role: Adaptation towards plant pathogenic or mutualistic lifestyle.

32
Q

Terpenes (Trichothecene)

A
  • 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.
33
Q

Ergotamine

A

Tryptophan derived metabolites

34
Q

Ergotamine source

A
  • Primarily associated with Claviceps purpurea.
  • infamous as a pathogen affecting rye, wheat, and various other crops.
35
Q

Ergotamine Pharmacological Effects:

A
  • Neurotransmitter Similarity: Shares similarities with neurotransmitters such as serotonin and epinephrine.
  • Ingestion Impact: Ingestion leads to convulsions, vasoconstriction, and hallucinations.
36
Q

Ergotamine Medical Applications

A
  • 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.
37
Q

Ergotamine)
*

A

BI441 (9 decks)

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