SecondarymetabolitesofFungi

MarliaSinggihWibowo

Fungalsecondarymetabolites
Secondarymetabolitesarecompounds
producedbyanorganismthatarenot
requiredforprimarymetabolicprocesses.
Fungiproduceanenormousarrayof
secondarymetabolites,someofwhichare
importantinindustry

 Manyfungiexpresssecondarymetabolites
thatinfluencecompetitiveoutcomes.
Thecompoundsareexpressedalongwith
enzymesnecessaryforextracellular digestion.
Theprecisefunctionofmanyofthese
compoundsinthenaturalenvironment,
however,isunclear.

 Secondarymetabolitesaregenerally
producedfollowingactivegrowth,andmany
haveanunusualchemicalstructure.Some
metabolitesarefoundinarangeofrelated
fungi,whileothersareonlyfoundinoneora
fewspecies.Therestricteddistributionimplies
alackofgeneralfunctionofsecondary
metabolitesinfungi.

 sixofthetwentymostcommonlyprescribed
medicationsareoffungalorigin.These
metaboliteshavebeensubjectedto
combinatorialchemistryfollowinggrowthin
selectivemedia.
Somemetabolitesaretoxictohumansand
otheranimals.Yetotherscanmodifythe
growthandmetabolismofplants.

Thepathway
Interestingly,themostimportantsecondary
metabolitesseemtobesynthesised fromone
oracombinationofthreebiosynthetic
pathways:polyketides arisingfromAcetyl
CoenzymeA,mevalonate pathwaythatalso
arisesfromAcetylCoenzymeA,andfrom
aminoacids.

 genesforthesynthesisofsomeimportant
secondarymetabolitesarefoundclustered
together,andexpressionofthecluster
appearstobeinducedbyoneorafewglobal
regulators.

Polyketide Metabolites
Polymerisation ofacetatemayresultinthe
formationofafattyacidorapolyketide.
Polyketides resultwhenaprimerotherthan
acetateisincluded,andprocessingduring
chainelongationresultsintheinclusionof
variousothercompounds.Thechainmaybe
furtherprocessedbycyclisation,lactonisation,
orformationofthioesters oramides.The
resultisastaggeringnumberofpossile
structuresbuiltfromthesimpleprimerunits.

 Includedamongthepolyketide secondary
metabolitesareorsellinic acid,
tetrahydroxynaphthalene (precursorfor
melanin),sterigmatocyctin,aflatoxins,statins,
andfumonisin.

Aflatoxin
Aflatoxins areproducedinmembersofthe
Aspergillus parasiticus groupviathe
polyketide pathway.Thepathwayhasaround
20steps,andtheendproductsincludea
diversityofrelatedcompounds
(bisfuranocoumarins)thatcanbereadily
convertedonetoanother.

 Aflatoxin B1isoneofthemosttoxiccompounds
known.Thetoxinisformedcommonlyinplant
materialsheldatrelativelyhighmoistureand
temperatureforlongperiods(ie growthin
tropicsandsubtropics).Peanuts,cornand
cottonarereadilycontaminatedinthefield.The
Aspergillus parasiticus groupoffungiare
commoninsoil.Thefungicancolonise rootsand
spreadthroughtheplant.Whenharvested,
contaminatedseedwillbecometoxicifnotdried
immediatelyandheldinadryform.

StructureofAflatoxin B1

 Aflatoxins aretoxicandcarcinogenic.
TheLSD50forducksis0.33mg/kg.Atlower
levelsandfollowingprolongedexposure,the
toxinscauselivercancerinhumans.
Aflatoxin B1isconvertedtoAflatoxin M(in
milk)onpassagethroughcows.Thoughless
toxic,itdoesillustratethepotentialdamage
causedbyconsumptionofcontaminated
product.

AromaticCompounds
Cycliccompoundscanbesynthesised viathe
polyketide orshikimic acidpathways.
Zearalenone isoneinterestingexamplefrom
thisgroup.Thecompoundregulates
perithecium formationinthefungus.Italso
hasanoestrogenic effectinmammals.

StructureofZearalenone

AminoAcidPathway
Penicillinandcephalosporinare lactam
antibiotics. lactam antibioticsareproduced
byafewAscomycota andseveralbacteria.
Theprecursorsoftheseantibioticsareamino
acids.Synthesisofactiveantibioticsis
directedbytheinclusioninthegrowth
mediumofdifferentorganicandfattyacids
resultingindifferentsidechainsonthe
compound.

 Asecondgroupofantibioticsderivedfromthe
aminoacidpathwayarethedefensins.
Defensins arepeptidesthatactagainst
bacteria.Theyarefoundinanimalswhere
theyfunctiontoprotectorganssuchasthe
gingiva wherebacterialdensitiesarevery
high.Thefirstdefensin foundinfungihas
beencalledplectasin.Theroleofplectasin in
itshostPseudoplectania nigrella isunknown.

 Toxinsderivedfromaminoacidsynthesis
includepsilocybin(Psilocybe)andBufotenine
(Amanita).
Thesecompoundsactonnerveimpulses,
resultinginhallucinations.Theresultis
thoughttobeduetothesimilaritiesbetween
thecompoundsandserotonin

CombinationofPathways
Ergotalkaloidsaresynthesised fromseveral
pathways.Trypotophan fromtheshikimic acid
pathwayisattachedtoanisoprenoid moiety
fromthemevalonate pathway,andseveral
aminoacidsfromprimarymetabolismareadded
dependingonthefinalproduct.Ergotalkaloids
areproducedasacomplexmixtureofrelated
compoundsfromabranchedpathway.
Theactivityofthealkaloidsisasvariedasthe
compounds.Inessence,thecompoundsmay
functionasvasodilators,hormoneregulators,
andfeedingdeterrents.Theycanbeactivein
mammalsandinsects.