The Chemistry of Mycotoxins

UMD Chemical Ecology

TIP Group 2A

What is a Mycotoxin?• Mycotoxins are toxic chemicals produced by fungi (molds),

that cause a wide variety of harmful effects.[1] • When ingested, they are known to cause: general toxic

affects, immune system suppression, mutations, cancer, and teratogenic affects (mutations in offspring). [1]

• Because many fungi are not well studied and not all species have been identified some researchers suggest that there could potentially be 300,000 mycotoxins. [2]

• There is no confirmed reason for the existence of mycotoxins. [2]

Why are they important?

•They are usually ingested in contaminated food•They can cause cancer, birth defects, liver damage, and nervous tissue damage, etc.•Most are not destroyed in normal cooking procedures.•Usually no treatment for mycotoxin poisoning•Mycotoxins have played an important role in some historical events (St. Anthony’s fire, Yellow rain, others)•Annual losses in the USA and Canada, arising from the impact of mycotoxins on the feed and livestock industries, are of the order of $5 billion. [1]

http://www.foodtech-international.com/papers/images/mycotoxins/figure1.gif

How do Mycotoxins cause damage to living organisms?

• Mycotoxins have unique chemical structures. These structures react/interact with the chemicals in living organisms causing harm.

http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/21738.jpg

Functional groups

• A functional group is a group of atoms that bonds to a carbon chain which changes the chemical properties of the carbon chain.

• Functional groups react in predictable ways

Common Functional groups

http://www.chemheritage.org/EducationalServices/pharm/tg/asp/ester/ester01.htm

How do mycotoxins cause other effects?

• Trichothecenes interfere with the active site of peptidyl transferase on ribosomes. This inhibits protein synthesis. [4]

• The special chemical structure that allows trichothecenes to bond to peptidyl transferase is the epoxytricothecene ring. [4]

• Since proteins (enzymes) catalyze almost every reaction in the body, not being able to produce enzymes can be very harmful.

Epoxytricothecene ring

Mycotoxins and livestockhttp://www.thebeefsite.com/articles/1808/mycotoxins-in-cattle

How do mycotoxins cause cancer?

• The chemical structure of some myxotoxins allows them to fit in between (intercalate) the double helix of DNA. This causes problems for DNA replication. Mutations in genes that control the cell cycle can lead to cancer.

• If the mutations happen in sperm and eggs they can cause birth defects or mutations in a person’s offspring.

http://4.bp.blogspot.com/_DZH2cmCoois/RqDJo5IavwI/AAAAAAAACl4/gIwPKe10FME/s400/DNA_intercalating_agent.jpg

Aflatoxins

Species: Genus Aspergillus, A. Flavus, A. parasiticus, A. Nomius

Affected foods: peanuts, maize, cottonseeds, spices

Aflatoxins M1, M2: Metabolites of aflatoxins B1 and B2:

Affects Milk and dairy products

Aflatoxins ContinuedInteresting facts:

• No animal species is immune to the acute toxic effects of aflatoxins including humans.

• Aspergillus can grow and produce aflatoxins on black pepper.

• In 1960 approximately 100,000 turkeys died as a result of eating peanut in their food that had aflatoxin. (Orginally thought to be caused by a virus and named Turkey X disease)

• Turkey X disease led to more research on mycotoxins.

Ochratoxin A

Species: P. Verrucosum and A. ochraceusFood affected: Cereals, coffee beans, and grapes.Interesting Facts: Ochratoxin can be transmitted from pork to humans by eating pork that is fed with contaminated food.

Zearalenone

Species : Fusarium roseum, F.graminearum, F. poae, F. culmorum

Food affected: corn, wheat, barley, oatsInteresting facts: • Zearalenone has estrogenic effects.• Fusarium species grows and produces mycotoxins at

times of high moisture 22% - 25%, and alternating high and low temp. (7-21ºC )

Patulin• Species: in the genus Aspergillus and

Penicillium• Food affected: Apple juice and apple

related products• Interesting Facts: One of the few

mycotoxins associated with apples.

Fumonisin B-1 B2

• Species: Many species from the Fusarium genus. Ex: F. verrucosum, F. proliferatum

• Affected foods: Maize (corn), wheat and other cereals

• Interesting facts: Inhibits an enzyme causing liver and kidney problems.

Trichothecenes• Species: Many species from the

Fusarium genus. Ex: F. sporotrichioides, F. poae, F. graminearum, F. culmorum.

• Foods affected: Maize (corn) Fusonisin toxin, Cereals, wheat

• Interesting facts: Can be produced in indoor environments, which can contribute to health problems among unsuspecting building occupants.

Trichothecene structure

http://en.wikipedia.org/wiki/Trichothecenes

Trichothecenes Cont.

• The damage to the immune systems of both rats and human could have caused decreased immune system response, which could have been a contributing factors that led to the high mortality during the Bubonic Plague. [4]

• Mycotoxin (T-2) caused an epidemic outbreak when grain that was supposed to be harvested in the fall was harvested in the following spring due to WWII. This extra time allowed fugal growth that contaminated the grain. [4]

Trichothecenes Cont.

• In 1981 secretary of state Alexander Haig alleged the Soviet Union supplied trichothecenes which were used as chemical weapons in Vietnam war. This was later disputed. [4]

Ergot• Species: Claviceps purpurea, and Aspergillus and

Penicillium• Affected foods: rye, barley, wheat, and oats• Interesting facts: • First documented case of ergot poisoning was in 857. [5]• Responsible for St. Anthony's fire. Monks of the order of St.

Anthony the Great specialized in treating ergotism victims. Some symptoms of ergotism are hallucinations and “rotting” of limbs which often lead to amputation. [5]

• Ergot contains a chemical precursor to lysergic acid (LSD).

Ergot Continued

• In 944 AD, in southern France, 40,000 people died of ergot poisoning. [5]

• Some people have speculated that ergot poisoning could have caused the strange behavior described during the Salem Witch Craft Trials. (you will research this later) [5]

Functional Group Assignment

• Identify the functional groups in mycotoxins provided.

Mycotoxin Assignment

• You are to read the articles provided by your teacher and answer the questions, followed by a discussion.

Extension Assignment• Research one of the following mycotoxin topics in greater

detail and write a one page summary. • Turkey X disease• St. Anthony’s fire• Yellow Rain• Salem Witch Craft Trials• Mycotoxins and biological weapons• Mycotoxins and the discovery of LSD• Mycotoxins and Religion- What effect did mycotoxins have

on historical religious activity? Give three examples

Interesting mycotoxin links• Yellow Rain –

http://cns.miis.edu/npr/pdfs/81tucker.pdf http://cns.miis.edu/stories/020805.htm

• Turkey X disease and yellow rain

www.botany.hawaii.edu/faculty/wong/BOT135/Lect09.pdf

• Historical mycotoxins, Ergot emphasis http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM

Resources• [1] Agriculture and Consumer protection [online]

www.fao.org/DOCREP/005/Y1390E/y1390e02.htm

• [2] Top ten [online] www.engormix.com/the_top_ten_most_e_articles_198_GDL.htm

• [4] Rocha O, Ansari K, Doohan F. 2005. Effects of trichothecene mycotoxins on eukaryotic cells: A review. Food Additives and Contaminants. 22[4]:369-378.

• [4] www.botany.hawaii.edu/faculty/wong/BOT135/Lect09.pdf

• [5]http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM