Here is an overview of all of the 76 parts we have used for this years project.
Click on the navigation bar below to see the different parts!
Parts from Professor Uffe Mortensen's Lab
The plasmids pFC330 (Nødvig et. al, 2015) and pFC902 (Nødvig et al., 2018) have built the foundation for our project. pFC330 is a plasmid containing an optimized Cas9 for our project. By coupling pFC330 to gRNA's made using the pFC902 as a template, one is able to make CRISPR-Cas9 mediated double stranded breaks to knock genes out of the genome. These parts have been designed, built and supplied by Uffe Mortensen's Lab. These parts are new to the iGEM registry.
CRISPR plasmid components
Part name
Part number
Short description
Aspergillus nidulans glycin tRNA
BBa_K3385002
tRNA spacer used to cleave transcribed sgRNA.
gRNA backbone
BBa_K3385003
gRNA backbone used for Cas9 mediated double-stranded breaks.
Aspergillus fumigatus U3 promoter
BBa_K3385004
Aspergillus fumigatus U3 promoter, chosen for it's ability to stimulate sgRNA production.
Aspergillus fumigatus U3 terminator
BBa_K3385005
Aspergillus fumigatus U3 terminator chosen for efficiency in generating sgRNA.
Ptef
BBa_K3385006
Promoter domesticated from Aspergillus nidulans.
Aspergillus niger Cas9
BBa_K3385007
Cas9 adapted from Streptococcus pyogenes and codon optimized for A. niger . This part is the very base for knocking out genes from the genome and was used for all our knockouts.
pyrG
BBa_K3385072
This is the selection marker pyrG, which is detrimental for pyrimidine biosynthesis.
E_coli_backbone
BBa_K3385073
This is the E. coli backbone used in pFC330 and pFC902. Includes ori and ampR
NLS
BBa_K3385074
It's a nuclear localization signal for Cas9, which ensures that the Cas9 is guided to the nucleus.
PacI/Nt.BbvCI cassette
BBa_K3385075
This is the PacI/Nt.BbvCI cassette which enables RE digestion of the pFC330 plasmid to insert the CRISPR constructs.
CRISPR-Cas9 backbone and CRISPR template plasmid
Part name
Part number
Short description
pFC330
BBa_K3385000
This Cas9 vector contains an A. niger codon optimized Cas9 for gRNA mediated knockout, the selection marker pyrG, and the plasmid replicator AMA1.
pFC902
BBa_K3385001
This vector was used as a template for the construction of the CRISPR parts for CRISPR-Cas9 mediated K/O of genes from the A. niger genome.
Morphology Toolbox
The Morphology toolbox has been built around the knock-out of specific genes. The gene sequences were found in aspgd.org (Cerqueira et al., 2014). The genes stem from A. niger or are orthologs from N. crassa and have been shown to affect morphology. The crRNA's have been designed to target the starting and ending positions of each of the seven genes. Below the crRNA's are the CRISPR and repair oligo combinations. The CRISPR construct needs to be integrated into pFC330 using the PacI/Nt.BbvCI cassette and transformed into A. niger protoplasts along with the repair oligos to complete the K/Os. To make double K/Os, one can:
However, the latter may show decreased efficiency, as more fragments need to enter the cells.
crRNA's
Part name
Part number
Short description
crRNA_chsC_KO_up
BBa_K3385012
crRNA targeting upstream chsC
crRNA_chsC_KO_down
BBa_K3385013
crRNA targeting downstream chsC
crRNA_spaA_KO_up
BBa_K3385016
crRNA targeting upstream spaA
crRNA_spaA_KO_down
BBa_K3385017
crRNA targeting downstream spaA
crRNA_gul-1_KO_up
BBa_K3385020
crRNA targeting upstream gul-1
crRNA_gul-1_KO_down
BBa_K3385021
crRNA targeting downstream gul-1
crRNA_arfA_KO_up
BBa_K3385024
crRNA targeting upstream arfA
crRNA_arfA_KO_down
BBa_K3385025
crRNA targeting downstream arfA
crRNA_racA_KO_up
BBa_K3385028
crRNA targeting upstream racA
crRNA_racA_KO_down
BBa_K3385029
crRNA targeting downstream racA
crRNA_aplD_KO_up
BBa_K3385032
crRNA targeting upstream aplD
crRNA_aplD_KO_down
BBa_K3385033
crRNA targeting downstream aplD
crRNA_pkaR_KO_up
BBa_K3385036
crRNA targeting upstream pkaR
crRNA_pkaR_KO_down
BBa_K3385037
crRNA targeting downstream pkaR
CRIPSR and repair oligo combinations
Part name
Part number
Short description
Repair oligo part number
CRISPR_chsC_KO
BBa_K3385014
Full guide construct for knockout of the Putitative Chitin synthase gene (chsC) in A. niger.
BBa_K3385015
CRISPR_spaA_KO
BBa_K3385018
Full guide construct for knockout of the Polarisome component gene (spaA) in A. niger.
BBa_K3385019
CRISPR_gul-1_KO
BBa_K3385022
Full guide construct for knockout of the uncharacterized N. crassa ortholog gul-1 gene (AN08g03530) in A. niger.
BBa_K3385023
CRISPR_arfA_KO
BBa_K3385026
Full guide construct for knockout of the Putative ADP-ribosylation factor gene (arfA) in A. niger.
BBa_K3385027
CRISPR_racA_KO
BBa_K3385030
Full guide construct for knockout of the Rho GTPase gene (racA) involved in regulation of cell polarity in A. niger.
BBa_K3385031
CRISPR_aplD_KO
BBa_K3385034
Full guide construct for knockout of the aplD gene, which encodes a transport involved protein, in A. niger.
BBa_K3385035
CRISPR_pkaR_KO
BBa_K3385038
Full guide construct for knockout of the regulatory subunit (repressor) of the cAPM-dependent protein kinase gene (pkaR) in A. niger.
BBa_K3385039
Protein Secretion Toolbox
Since we chose glaA as our reporter protein, a K/O was needed. The K/O was realised using the already mentioned pFC330 with a CRISPR construct consisting of two sgRNA's targeting the upstream and downstream of glaA. The signal peptides should be integrateable in front of any protein, such as the homologous glucoamylase or the hetrologous mCherry or GFP.
Glucoamylase
Part name
Part number
Short description
crRNA_glaA_KO_up
BBa_K3385008
crRNA targeting upstream glaA
crRNA_glaA_KO_down
BBa_K3385009
crRNA targeting downstream glaA
CRISPR_glaA_KO
BBa_K3385010
CRISPR_glaA_KO
glaA_repair_oligo
BBa_K3385011
Repair oligo to be used in combination with pFC330 with CRISPR_glaA_KO integrated.
Gene_glaA
BBa_K3385040
Glucoamylase gene from A. niger
Gene_glaA_SigP
BBa_K3385041
Glucoamylase gene from A. niger with its native signal peptide
Signal Peptides
Part name
Part number
Short description
SigP_glaA
BBa_K3385042
Signal peptide for Glucoamylase (glaA).
SigP_faeA
BBa_K3385043
Signal peptide for Feruloylesterase A (faeA).
SigP_pmeA
BBa_K3385044
Signal peptide for Pectinesterase (pmeA).
SigP_pgaI
BBa_K3385045
Signal peptide for Endopolygalacturonase I (pgaI).
SigP_xlnD
BBa_K3385046
Signal peptide for Exo-1,4-beta-xylosidase (xlnD).
SigP_lacA
BBa_K3385047
Signal peptide for Beta-galactosidase (lacA).
SigP_eglA
BBa_K3385048
Signal peptide for Xyloglucan-specific endo-beta-1,4-glucanase A (eglA).
SigP_eglB
BBa_K3385049
Signal peptide for Endo-beta-1,4-glucanase B (eglB).
SigP_cbhA
BBa_K3385050
Signal peptide for 1,4-beta-D-glucan cellobiohydrolase A (cbhA).
SigP_cbhB
BBa_K3385051
Signal peptide for 1,4-beta-D-glucan cellobiohydrolase B (cbhB).
SigPower
BBa_K3385052
This synthetic signal peptide was predicted by the model SignalPrepper.
SigPilot
BBa_K3385053
This synthetic signal peptide was predicted by the model SignalPrepper.
SigPineapple
BBa_K3385054
This synthetic signal peptide was predicted by the model SignalPrepper.
SigPeanut
BBa_K3385055
This synthetic signal peptide was predicted by the model SignalPrepper.
SigPuppy
BBa_K3385056
This synthetic signal peptide was predicted by the model SignalPrepper.
Integration Parts
Part name
Part number
Short description
T1G3R_SglaA_glaA
BBa_K3385057
Insert of glaA expression cassette for A. niger. It is made to be integrated in albA, which will lead to white/yellow conidia upon correct integration in the genome.
T1G3R_SfaeA_glaA
BBa_K3385058
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_faeA.
T1G3R_SpmeA_glaA
BBa_K3385059
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_pmeA.
T1G3R_SpgaI_glaA
BBa_K3385060
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_pgaI.
T1G3R_SxlnD_glaA
BBa_K3385061
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_xlnD.
T1G3R_SlacA_glaA
BBa_K3385062
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_lacA.
T1G3R_SeglA_glaA
BBa_K3385063
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_eglA.
T1G3R_SeglB_glaA
BBa_K3385064
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_eglB.
T1G3R_ScbhA_glaA
BBa_K3385065
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_cbhA.
T1G3R_ScbhB_glaA
BBa_K3385066
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigP_cbhB.
T1G3R_Spower_glaA
BBa_K3385067
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigPower.
T1G3R_Spilot_glaA
BBa_K3385068
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigPilot.
T1G3R_Spineapple_glaA
BBa_K3385069
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigPineapple.
T1G3R_Speanut_glaA
BBa_K3385070
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigPeanut.
T1G3R_Spuppy_glaA
BBa_K3385071
Insert of glaA expression casette for A. niger, with its signal peptide changed to SigPuppy.
References
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Nødvig, C., Nielsen, J., Kogle, M., & Mortensen, U. (2015). A CRISPR-Cas9 System for Genetic Engineering of Filamentous Fungi. PLOS ONE, 10(7). doi:10.1371/journal. Pone.0133085
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Nødvig, C., Hoof, J., Kogle, M., Jarczynska, Z., Lehmbeck, J., Klitgaard, D., & Mortensen, U. (2018). Efficient oligo nucleotide mediated CRISPR-Cas9 gene editing in Aspergilli. Fungal Genetics And Biology, 115, 78-79. doi: 10.1016/j.fgb.2018.01.004
- Cerqueira, G., Arnaud, M., Inglis, D., Skrzypek, M., Binkley, G., & Simison, M. et al. (2014). The Aspergillus Genome Database: multispecies curation and incorporation of RNA-Seq data to improve structural gene annotations. Nucleic Acids Res., 42(1). doi: 10.1093/nar/gkt1029