Fusarium
Mycotoxins:


Vomitoxin



Nivalenol



Lycomarasmin



Fusariotoxin
T2-Toxin,



Fusaric Acid



Fumonisin B1


New! Fusarium mycotoxins: chemical names list.


Chemical Herbicides


Soil Solarization


Español


This site is supported by a grant from Drug Policy Reform Fund of the TIDES Foundation.

 

MYCOTOXINS:
Note:
I
n the absence of hard data on mycotoxins potentially present in the Fusarium oxysporum and Pleospora papaveraceae strains being considered for use as mycoherbicides against drug crops, we can only speculate on what these strains may contain.  Below, therefore, is our informed speculation based upon previous research on Fusarium mycotoxins.           

Mycotoxins in general:

Mycotoxins are the toxic chemicals produced by fungi for a variety of reasons. These include to attack or gain access to hosts by helping to dissolve cell membranes, or as protective measures against encroaching organisms. The production of mycotoxins within the fungus depends on food sources and the particular enzymes of the fungus and other environmental factors.  Mycotoxins are usually not found in spores, but are generally produced in the next stage, that of mycelium.  Many mycotoxins, such as Mycotoxin T2 (Fusariotoxin) or the Amanita-toxins can be lethal to animals.  Others, such as Psilocybin, are entheogenic, producing altered states of consciousness that are usually associated with shamanism/religion.  Others, such as the ergot derivatives are used for migraine and post-partum hemorrhage. Still others, such as penicillin, Fusaric acid, and Wortmannin have antibiotic effects, and Zearalenone with anabolic effects, but which may or may not be beneficial to the host organism depending on the mode of administration and dose.  By definition, only  mycotoxin-producing fungi can be used as mycoherbicides to attack, colonize and kill plants.

The most-studied mycotoxins in Fusarium are toxic to both plants and animals.  Some have antibiotic properties.  The mycotoxins of Pleospora have yet to be identified, but we know from reports in the lab where it is being researched that it has toxic effects on humans.  After over a decade of work on EN-4 (a "coca-killing" strain of Fusarium oxysporum forma specialis erythroxyli), the USDA has neglected to examine strain EN-4 mycotoxins.  And by ignoring this research, an ARS spokesperson was still able to repeat the written USDA "talking points" mantra which state that EN-4 does not produce or contain mycotoxins dangerous to animals or humans to various members of the press. This claim is disavowed by her superiors, such as Eric Rosenquist, who candidly offers that the work on the safety of EN-4 as a mycoherbicide, including tests on its mycotoxins --have yet to be done.

In the absence of hard data on mycotoxins present in the Fusarium oxysporum and Pleospora papaveraceae strains being considered for use as mycoherbicides, we can only speculate on what these strains may contain. We also must caution the reader that fungi can produce different toxins and varying amounts of toxins depending on which media they are growing on, humidity, temperature, and light, among other variables. Even the USDA has published on this phenomenon: "Cultures of F. proliferatum established from these samples produced fumonisins when cultured on rice. They also produced other toxins, including moniliformin and beauvericin, which were not found in naturally-infected field samples of rice. It is not known why moniliformin and beauvericin were not found in field samples. There may be mechanisms by which viable rice kernels suppress synthesis of moniliformin and beauvericin by F. proliferatum, that are not operative in autoclaved rice cultures. A better understanding of the mechanisms by which mycotoxin production is controlled in Fusarium sp. may lead to methods to control these compounds in food and feed.". USDA has yet to persue this research.

However, here, for comparison's sake and taking the aforementioned caveats about the variability of Fusaria into consideration, we may examine the series of mycotoxins that have been already isolated from Fusarium oxysporum and other Fusarium species.

Fusarium mycotoxins:

"The genus Fusarium contains important mycotoxin-producing species that have been implicated in human diseases, such as alimentary toxic aleukia, Urov or Kashin-Beck disease, Akakabi-byo or scabby grain intoxication, and esophageal cancer. Many of these mycotoxin-producing species have also been implicated in several animal diseases, including hemorrhagic, estrogenic, emetic, and feed refusal syndromes, fescue foot, degnala disease, moldy sweet potato toxicosis, bean hulls poisoning, and equine leukoencephalomalacia. The interest in toxigenic Fusarium species is increasing world-wide due to the discovery of a growing number of naturally occurring Fusarium mycotoxins that have practical importance as threats to human and animal health."  quoted from Toxigenic Fusarium Species by Marasas et alia, Penn State U, 1984

Chemical Names of Fusarium Mycotoxins from Marasas et al. and other sources (Toxigenic Fusarium Species by Marasas et alia, Penn State U, 1984). Some of the names are redundant, and some are the result of research in different countries where two or more names have been given to the same compound, a common phenomenon in science.

  • 4-Acetoxyscirpenediol = 4$-3-acetoxy-3", 15-dihydroxy-12,13-epoxytrichothec-9-ene. A similar compound, monodeacetylanguidin = 4- or 15-acetylscirpentriol.
  • 3-Acetyldeoxynivalenol (= Deoxynivalenol monoacetate) = 3"-acetoxy-7",15-dihydroxy-12,13-epoxytrichothec-9-en-8-one
  • 8-Acetylneosolaniol (= Neosolaniol monoacetate) = 4$,8", 1 5-triacetoxy-3"-hydroxy-1 2,13-epoxytrichothec-9-ene
  • 4- or 15-Acetylscirpentriol. See 4-Acetoxyscirpenediol
  • Acetyl T-2 toxin = 3",4$,15-triacetoxy-8"-(3-methylbutyry(oxy)-1 2,1 3-epoxytricho-thec-9-ene
  • Anguidin. See Diacetoxyscirpenol.
  • Avenacein +1
  • Beauvericin +2
  • Butenolide = 4-acetamido-4-hydroxy-2-butenoic-acid -(-lactone.
  • Calonectrin = 3", 1 5-diacetoxy-12,13-epoxytrichothec-9-ene.
  • 15-Deacetylcalonectrin (= 1 5-De-0-acetylcalonectrin) = 3"-acetoxy-1 5-hydroxy-12,13-epoxytrichothec-9-ene.
  • Deoxynivalenol (= Rd toxin, = Vomitoxin) = 3",7",15-trihydroxy-12,13-epoxytricho-thec-9-en-8-one
  • Deoxynivalenol diacetate. See Diacetyldeoxynivalenol
  • Deoxynivalenol monoacetate. See 3-Acetyldeoxynjvalenol
  • Diacetoxyscirpendiol See 7"-Hydroxydiacetoxyscirpenol
  • Diacetoxyscirpenol (= Anguidin) = 4$,15-diacetoxy-3"-hydroxy12,13-epoxytrjchothec-9-ene.
  • Diacetoxyscerpentriol See 7",8"-Dihydroxydiacetoxyscirpenol
  • Diacetyldeoxynivalenol (= Deoxynivalenol diacetate) = 3",15-diacetoxy-7-hydroxy 12,13-epoxytrichothec-9-en-8-one.
  • Diacetylnivalenol (= Nivalenol diacetate) = 4$,15-diacetoxy-3",7"-dihydroxy-12,13-epoxytrichothec-9-en-8-one
  • 7",8"-Dihydroxydiacetoxyscirpenol (= Diacetoxyscirpentriol) = 4$,15-diacetoxy-3",7",8"-trihydroxy-12,13-epoxytrichothec-9-ene
  • Enniatins +1
  • Fructigenin +1
  • Fumonisin B1 1 1,2,3-propanetricarboxylic acid 1,-l-[1-(12-amino-4,9,11-trihydroxy-2-methyltridecyl)-2-(1-methylpentyl)
    -1,2-ethanediyl] ester; macrofusine +
  • Fusarenon. See Fusarenon-X.
  • Fusarenon-X (=Fusarenon, = Monoacetylnivalenol, = Nivalenol monoacetate) = 4$-acet oxy-3",7", 15-trihydroxy-12,13-epoxytrichothec9en8one
  • Fusaric acid (= Fusarinic acid) = 5-butylpicolinic acid.
  • Fusarinic acid. See Fusaric acid.
  • F-2. See Zearalenone
  • HT-2 toxin = l5-acetoxy-3",4$-dihydroxy-8"-(3-methylbutyryloxy)-12$-epoxytricho-thec-9-ene.
  • 7"-Hydroxydiacetoxyscirpenol (= Diacetoxyscirpendiol) = 4$,15-diacetoxy-3",7"-dihydroxy-12,13-epoxytrichothec-9ene
  • 8"-Hydroxydiacetoxyscirpenol See Neosolaniol.
  • 1,4-Ipomeadiol = 1-(3-furyI)-1 ,4-pentanediol
  • Ipomeanine = 1-(3-furyl)-1 ,4-pentanetione.
  • 1-Ipomeanol = 1-(3-furyl)-1-hydroxy-4-pentanone
  • 4-lpomeanol = l-(3-furyl)-4-hydroxy4pentanone
  • Lateritin +1 
  • Lycomarasmin +1
  • Moniliformin = potassium or sodium salt of 1-hydroxycyclobut-1-ene-3,4-dione
  • Monoacetoxyscirpenol = 15-acetoxy-3",4$~djhydroxy-12,13-epoxytrichothec-9ene
  • Monoacetylnivalenol See Fusarenon-X
  • Monodeacetylanguidin. See 4-Acetoxyscirpenediol
  • Neosolaniol (= 8"-Hydroxydiacetoxyscirpenol) = 4$,15-diacetoxy-3"8"-dihydroxy 12,13-epoxytrichothec-9-ene
  • Neosolaniolacetate See 8-Acetylneosolaniol
  • Neosolaniol monoacetate. See 8-Acetylneosolaniol
  • Nivalenol = 3",4$,7", 15-tetrahydroxy-12,13-epoxytrichothec-9-en-8-one
  • Nivalenol diacetate See Diacetylnivalenol
  • Nivalenol monoacetate See Fusarenon-X
  • NT-1 toxin (=T-1 toxin) = 4$, 8"-diacetoxy-3",15-dihydroxy-12,13-epoxytrichothec-9-ene
  • NT-2 toxin = 4$-acetoxy-3", 8", 1 5-trihydroxy-1 2,1 3-epoxytrichothec-9-ene
  • Rd toxin See Deoxynivalenol
  • Sambucynin +1
  • Scirpentriol = 3",4$, 1 5-trihydroxy-12,13-epoxytrichothec-9-ene
  • Solaniol See Neosolaniol
  • T-1 toxin See NT-1 toxin
  • T-2 toxin = 4$,15-diacetoxy-3"-hydroxy-8"-(3-methylbutyrlyloxy)-12,13-epoxytrichothec-9-ene
  • Triacetoxyscirpendiol = 4$,8",15-triacetoxy-3",7"-dihydroxy-1 2,1 3-epoxytrichothec-9-ene
  • Triacetoxyscirpenol = 3", 4$,15-triacetoxy-12,13-epoxytrichothec-9-ene
  • Vomitoxin See Deoxynivalenol
  • Yavanicin  +1
  • Zearalenol = 2,4-dihydroxy-6-(6, 1O-dihydroxy-trans-1 -undecenyl)-benzoic acid :-lactone
  • Zearalenone = 6-(10-hydroxy-6-oxo-trans-1-undecenyl)-$-resorcylic acid lactone

+ Other source
+1 N.A.Krasil'nikov, Soil Microorganisms and Higher Plants
+ Abbas et al.

Mycotoxins reported from Fusarium oxysporum:

  • Diacetoxyscirpenol *
  • Diacetylnivalenol *
  • 7",8"-Dihydroxydiacetoxyscirpenol *
  • Fumonisin B1 +
  • Fusarenon-X *
  • Fusaric acid *
  • 7"-Hydroxydiacetoxyscirpenol *
  • Moniliformin *
  • Neosolaniol *
  • T-2 toxin *
  • Zearalenone *

*  Marasas et al. Toxigenic Fusarium Species by Marasas et alia, Penn State U, 1984

Chemistry and toxicology of the Fusaria mycotoxins:

The mycotoxins produced by Fusarium species are structurally quite varied.  Often, there is a series of  closely related compounds which can be identified as a group, such as the Trichothecenes which lack nitrogen in their structure and Fumonisins and Lycomarasmins, which posses amine functions.  Rather than approach this field by chemical category or structure, we shall resort to an alphabetical listing of the compounds by their most-used common names, as registered in the Merck Index, Twelfth Edition, which we will quote extensively here.

Fusarium mycotoxins may leach into the soil, causing damage to plants and animals through leaching even after the fungus is no longer active.  Indeed, a very real risk may be extrapolated for humans, also.

 

Fusaric Acid

Fusaric Acid. 
"5-Butyl-2-pyndinecarboxylic acid
; 5-butylpicolinic acid. C10H13N02; mol wt 179.22. C 67.02%, H 7.31%, N 7.82%, 0 17.85%. Antibiotic (wilting agent) first isolated from the fungus Fusarium heterosporium, Nees: Yabuta et al., J. Agr. Chem. Soc. Japan 10, 1059 (1934). Isoln from other Fusarium species and from Gibberella fujikuroi and synthesis: Plattner et al, Helv. Chim. Acta 37, 1379 (1954). Prepn: Hardegger, Nikles, ibid. 39, 505 (1956); 40, 2428 (1957); Schreiber, Adam, Ber. 93, 1848 (1960); Umezawa, Nagatsu, Ger. pat. 2,005,255 (1970 to Microbiochem. Res. Found.); R. Tschesche, W. Führer, Ber. 111, 3502 (1978). Dopamine-hydroxylase inhibitor and hypotensive activity: Suda et al., Chem. Pharm. Bull. 17, 2377 (1969); Nagatsu et al, Biochem. Pharrnacol. 19, 35 (1970). Toxicity study: Ishii et al. Arzneimittel-Forsch. 25, 55 (1975).
Colorless crystals, mp 96-98°. LD50 orally in mice: 230 mg/kg (Ishii).
Copper Salt, bluish violet crystals from water, mp258-259°." Merck Index, Twelfth Edition


Fumonisin B1

Fumonisin B1. 
"1,2,3-propanetricarboxylic acid 1,-l-[1-(12-amino-4,9,11-trihydroxy-2-methyltridecyl)-2-(1-methylpentyl)
-1,2-ethanediyl] ester
; macrofusine; F B1. C34H59NO15 mol wt 721.84. C 56.57%, H 8.24%, N 1.94%, 0 33.25%. Most prevalent of a family of mycotoxins produced by Fusarium moniliforme, a common mold associated with corn; also isolated from other Fusarium species. Isolation: W.C. A. Gelderblom et al, Appl. Environ. Microbiol. 54, 1806 (1988). Structure elucidation of family: S. C. Bezuidenhout et al., Chem. Commun. 1988, 743. Causative agent of pulmonary edema in pig: L. R. Harrison et al, J. Vet. Diagn. Invest. 2, 217 (1990). Association of B1, B2 with human esophageal cancer: J. P. Rheeder et al, Phytopathology 82, 353 (1992). Metabolism: G. S. Shephard et al, Toxicon. 30, 768 (1992). Toxicity and carcinogenicity in rat: W.C. A. Gelderblom et al, Carcinogenesis 12, 1247 (1991). Toxicology in pig: W. H. Haschek et al, Mycopathologia 117, 83 (1992). LC determn in corn of B series fumonisins: M.E. Stack, R. M. Eppley, J. Assoc. Offic. Anal Chem. 75, 834 (1992); P. A. Murphy et al., J. Agric. Food Chem. 41, 263 (1993). Review of animal toxicoses: P. F. Ross et al., Mycopathologia 117, 109-114 (1992). Review: W. P. Norred, J. Toxicol Environ. Health 38, 309-328 (1993)." Merck Index, Twelfth Edition

Also see:  NC-129 Fusarium mycotoxins in cereal grains

and:  

Reduction of Fusarium Mycotoxins as concerns in Agricultural Commodities. 

and:

Fumonisin in US corn: Corn toxin examined in border birth defects: Diet may have put Hispanics at risk


T-2 Toxin, Fusariotoxin, Mycotoxin T-2

T-2Toxin.
"(3",4$,8")-12,13,-Epoxytrichothec-9-ene-3,4,8,15-tetrol 4,15-diacetate 8-(3-methylbutanoate); 3" -hydroxy -4$, 15-diacetyloxy-8"-(3-methylbutyryloxy)-12,13-epoxy -)9 -tricothecene; 8"-(3-methylbutyryloxy)-4$, I 5-diacetoxyscirp-9-en-3"-ol; fusariotoxin T-2; insariotoxin; mycotoxin T-2; NSC-138780. C24H34O9; mol wt 466.53. C 61.79%, H 7.35%, 0 30.87%. Trichothecene mycotoxin isolated from Fusarium tricinctum: J. R. Bamburg et al, Tetrahedron 24, 3329 (1968). Physicochemical data: A. E. Pohland et al, Pure Appl. Chem. 54, 2119 (1982). Synthesis: M.C. Wani et al., J. Org. Chem. 52, 3468 (1987). Biosynthetic study: F. Van Middlesworth et al., J. Org. Chem. 55, 1237 (1990). Toxicology studies: W. F. 0. Marasas et al., Toxicol. Appl. Pharmacol. 15, 471 (1969); H. B. Schiefer, D. S. Hancock, ibid. 76, 464 (1984); D. A. Creasia et al, Fund. Appl. Toxicol 14, 54 (1990). Implicated as a chemical warfare agent in Southeast Asia with nivalenol, q.v.: N. Wade, Science 214, 34 (1981); R. T. Rosen, J. D. Rosen, Biomed Mass Spectrum. 9, 443 (1982). Review: Developments in Food Science vol. 4, Y. Ueno, Ed., entitled "Trichothecenes: Chemical, Biological and Toxicological Aspects" (Kodansha Ltd. and Elsevier, New York, 1983) 310 pp. Review of pharmacokinetics and metabolism: B. Yagen, M. Bialer, Drug Metab. Rev. 25, 281-323 (1993).

Crystals, mp l51-152°. ["]26/D = 15° ( c = 2.58 in ethanol). Freely soluble in ethyl alcohol, ethyl acetate, chloroform, DMSO and other organic solvents; slightly soluble in petroleum ether; very slightly soluble in water. LD50 orally in female rats: 4.0 mg/kg (Marasas). LD50 (mg/kg) in mice: 5.2 i.p., 4.2 i.v.; in rats: 7.0 intragastric, 0.9-1.3 i.p., 0.9 iv., 2.0 s.c.; in guinea pigs: 3.0-4.0 orally, 5.3 intragastric, 1.0 i.m., 1.0-2.0 i.v., 1.0-2.0 s.c.; in pigs: 5.0 orally, 3.0 iv. (Yagen, Bailer).

Caution: May be highly irritating to skin and mucous nembranes. Direct contact may cause extensive inflammation and tissue necrosis (Marasas). Topical exposure has lead to systemic toxicity and death in experimental animals (Scheiffer, Hancock)." Merck Index, Twelfth Edition


Lycomarasmin

Lycomarasmine.

" N-[2-[(2-Amino-2-oxoethyl)-amino]-2-carboxyethyl]-L-aspartic acid; Welkstoff. C9H15N3O7; mol wt 277.23. C 38.99%, H 5.45%, N 15.16%, O 40.40%. Antibiotic peptide (tomato-wilting agent) produced by the fungus Fusarium lycopersici. Isoln: Plattner. Clauson-Kaas, Helv. Chim. Acta 28, 188 (1945). Structure: eldem. Experientia 1, 195 (1945); Hardegger et al, Helv. Chim. Acta 46, 60 (1963). 
Crystals, dec 227-229°. [" ]20/D - 42° to -48° (aq. Soln at pH7). Acid reaction. Sparingly sol in water; freely sol in dil acids or alkalies."
  Merck Index, Twelfth Edition


Nivalenol

Nivalenol.

"(3",4B, 7")-1 2,13-Epoxy-3,4,7,15-tetra-hydroxytrichothec-9-en -8-one;

3",4$,7", I 5-tetrahydroxyscirp-9-en-8-one. C15H20O7; mol wt 312.32. C 57.69%, H 6.45%, 0 35.86%. Trichothecene mycotoxin isolated from Fusarium nivale: T. Tatsuno et al., Chem. Pharm. Bull. 16, 2519 (1968). Structure: eidem, Tetrahedron Letters 1969, 2823. Toxicology: T. Tatsuno, Cancer Res. 28, 2393(1968). Implicated as a chemical warfare agent in Southeast Asia with T-2 toxin, q.v.: N. Wade, Science 214, 34 (1981); R.T. Rosen, J. D. Rosen, Biomed. Mass Spectrom. 9, 443(1982).

Crystals, mp 222-223° (dec). ["]24/D +21.54° (c = 1.3 in ethanol). uv max (methanol): 218 nm (, 6300). Slightly sol in water; sol in polar organic solvents. LD50 i.p. in mice: 40 :g/1O g (Tatsuno).

Caution: Potential symptoms of overexposure include fever, nausea, vomiting, diarrhea, leukopenia, bleeding, sepsis; necrotic lesions of skin and mucosa. See M. J. Ellenhorn, D. G. Barceloux in Medical Toxicology: Diagnosis and Treatment of Human Poisoning (Elsevier, New York, 1988) pp. 1312-1314."  Merck Index, Twelfth Edition


Vomitoxin

Vomitoxin. 

"12,13.Epoxy-3,7,15-trihydroxytrichothec-9-en-8-one; deoxynivalenol; dehydronivalenone. C15H20O6; mol wt 296.32. C 60.80%, H 6.80%, 0 32.40% Isoln of the trichothecene mycotoxin from Fusarium roseum and structure: N. Morooka et al, J. Food Hyg. Soc Japan 13, 368 (1972); T. Yoshizawa, N. Morooka, Agr. Biol. Chem 37, 2933 (1973). Isoln from F. graminearum R. F. Vesonder et al, Appl. Microbiol. 26, 1008 (1973); eidem, Appl. Environ. Microbiol. 31, 280 (1976). Emetic and refusal activity in swine: D. M. Forsyth et al., ibid. 34, 547 (HPLC analysis: G. A. Bennett et al, J. Am. Oil Chem Soc. 58, 1002A (1981). Implicated as a chemical warfare agent with nivalenol, q.v. in Southeast Asia: N. Wade, Science 214, 34 (1981).

Fine needles from ethyl acetate + petr ether, mp 151-153°. [a]25/D+6.35 (c=0.07 in ethanol) uv maxd (ethanol): 218 nm (e 4500). LD50 i.p. in male, female mice (mg/kg): 70.0, 76.7 (Yoshizawa, Marooka)."  Merck Index, Twelfth Edition