LECTURE 10 Secondary Metabolite Gene Clusters Flashcards
The biosynthesis genes for fungal secondary metabolites are located where?
in clusters
The size of gene clusters
10 kbp- 70 kbp
what is an exception?
two separate gene clusters located on different chromosomes are required for the biosynthesis of the meroterpenoids austinol and dehydroaustinol
Most of the clusters contain one or several central biosynthesis genes encoding what?
large multidomain, multimodular enzymes belonging to the PKS or NRPS
what do some secondary metabolites require for their biosynthesis
trans-prenyltransferases
biosynthesis of ergot alkaloids
requires a tryptophan dimethylallyltransferase that catalyses the prenylation of I- Tryptophan
The transcription factors of SM gene clusters are often
zinc finger TFs
example of zinc finger TFs
- Cys2His2
- Fungal Zn2Cys6
Many of the fungal secondary metabolism gene clusters encode
a single transcription factor
two regulatory zinc finger proteins for Aflatoxin gene cluster in A. flavus & A. parasiticus
aflR and aflS
Sterigmatocystin gene cluster in
A. nidulans
the gliotoxin biosynthesis genes are arranged in a cluster consisting of
13 genes regulated by zinc finger transcription factor GliZ in A. fumigatus
Deletion of the GliZ-encoding gene results in
the loss of gliotoxin production
OE of the GliZ-encoding gene results in
a substantial increase in the gliotoxin level
examples of carcinogenic PKS compounds
AflatoxinandSterigmatocystin
β-Lactam antibiotics are produced by
both filamentous fungi and
bacteria, including Gram-negative and Gram-positive microorganisms
list the three amino acids Penicillins and cephalosporins are synthesized from
l-α-aminoadipic acid (l-α-AAA), l-cysteine and l-valine
These precursors are condensed to
the tripeptide δ-(l-α-aminoadipyl)-l- cysteinyl-d-valine (ACV) catalysed by a single enzyme, ACV synthetase (ACVS).
what are ACVS encoded by
a single structural gene designated acvA (pcbAB)
what occurs In the second step?
oxidative ring closure of the linear tripeptide leads to formation of a bicyclic ring
where and when were Secondary metabolite superclusters First discovered
in A. fumigatus in 2013
FTC C is a fungal toxin of the
diketopiperazines family of compounds
in mammalian cells, FTC is
tremorgenic and causes cell cycle arrest.
Fumitremorgin C is a specific, selective, and potent inhibitor at micromolar concentrations of the
breast cancer resistant protein (BCRP/ABCG2), an ABC transporter associated with chemotherapy resistance.
