The tool is dividied in multiple sections. The upper part contains the TU to be selected by the user, clicking the color squares.
The middle are is the blackboard where it is possible to select the receptor vector, the structure and the parts to create a construction. And the bootom part is the section with the multiple actions to do with the construction.
Note: This wizard allows the assembly of maximun of 6 TUs, the process to create a more complex assembly can be found in (Blazquez et al 2022)
Golden Standard contains three possibilities, PUC, RK2 y pBRR1
The user can select the option to design a basic structure with promoter, RBS, cds and terminator or include tags in N-terminal or C-terminal position.
Based on the structure selection, the construction showed in the bottom panel is changing to acomodate the new parts.
The first step is the TU selection clicking on the colored squares in the top section.
- Click on a specific part (squared name) and select a element. It can be repeated as many times as elements to edit. The following image shows the output of the process after selection of the promoter Pem7, the RBS T7RBS, and so on. It is important to select the right parts based on their fusion sites, for example, if N-Tag is included, only a RBS with a BC fusion site is right. The tool shows all of them but only a RBS with a BC fusion site can give a right construction.
When a new sequence is included into the server some previous steps are required to perform a correct assembly.
Part |
Position |
modifications |
Fixed sequences |
Manual check point |
|
Promoter |
AB |
Remove restriction enzymes |
5' |
GGTCTCAGGAG |
|
3' |
TACTAGAGACC |
|
|||
RBS |
BD |
Remove restriction enzymes |
5' |
GGTCTCATACT |
|
3' |
AATGAGAGACC |
|
|||
CDS |
DG |
Remove restriction enzymes |
5' |
GGTCTCAAATG |
stop codon included |
Remove ATG from sequence |
3' |
GCTTAGAGACC |
|
||
Terminator |
GI |
Remove restriction enzymes |
5' |
GGTCTCAGCTT |
|
3' |
CGCTAGAGACC |
|
2. If the assembly contains tags:
2.1 One N-tag:
The sequence require the following modifications, change the sequence according the type of the part.
Number of tags | Part type | Position | modifications | orientation | Fixed sequences | Manual check point | |
---|---|---|---|---|---|---|---|
1 x N-Tag |
Promoter |
AB |
|
5' |
GGTCTCAGGAG |
|
|
3' |
TACTAGAGACC |
|
|||||
RBS |
BC |
|
5' |
GGTCTCATACT |
Distance to ATG |
||
3' |
CCATAGAGACC |
|
|||||
N-tag_1 |
CD |
Remove ATG from original sequence |
5' |
GGTCTCACCATg |
Reading frame |
||
|
3' |
gcAATGAGAGACC |
|
||||
CDS |
DG |
Remove ATG from original sequence |
5' |
GGTCTCAAATG |
Reading frame |
||
|
3' |
GCTTAGAGACC |
stop codon included |
||||
|
|
|
|||||
Terminator |
GI |
|
5' |
GGTCTCAGGCT |
|
||
3' |
CGCTAGAGACC |
|
|||||
2x N-tags |
Promoter |
AB |
|
5' |
GGTCTCAGGAG |
|
|
3' |
TACTAGAGACC |
|
|||||
RBS |
BC |
|
5' |
GGTCTCATACT |
Distance to ATG |
||
3' |
CCATAGAGACC |
|
|||||
N-tag_1 |
CD |
Remove ATG from original sequence |
5' |
GGTCTCACCATg |
Reading frame |
||
|
3' |
gcAATGAGAGACC |
|
||||
N-tag_2 |
DE |
Remove ATG from original sequence |
5' |
GGTCTCAAATG |
Reading frame |
||
|
3' |
tcAGGTAGAGACC |
|
||||
CDS |
EG |
Remove ATG from original sequence |
5' |
GGTCTCAAGGTcg |
stop codon included |
||
|
3' |
GCTTAGAGACC |
|
||||
Terminator |
GI |
|
5' |
GGTCTCAGCTT |
|
||
3' |
CGCTAGAGACC |
|
|||||
1 x C-Tag |
Promoter |
AB |
Remove ATG from original sequence |
5' |
GGTCTCAGGAG |
|
|
3' |
TACTAGAGACC |
|
|||||
RBS |
BD |
|
5' |
GGTCTCATACT |
Distance to ATG |
||
3' |
AATGAGAGACC |
|
|||||
CDS |
DF |
Remove ATG from original sequence |
5' |
GGTCTCAAATG |
|
||
|
3' |
TTCGAGAGACC |
No stop codon |
||||
|
|
|
|
||||
C-tag_1 |
FG |
|
5' |
GGTCTCACCATgc |
Reading frame |
||
|
3' |
GCTTAGAGACC |
Stop codon included |
||||
Terminator |
GI |
|
5' |
GGTCTCAGCTT |
|
||
3' |
CGCTAGAGACC |
|
|||||
2x C-tags |
Promoter |
AB |
|
5' |
GGTCTCAGGAG |
|
|
3' |
TACTAGAGACC |
Distance to ATGHola |
|||||
RBS |
BD |
|
5' |
GGTCTCATACT |
|
||
3' |
AATGAGAGACC |
|
|||||
CDS |
DF |
Remove restriction enzymes |
5' |
GGTCTCAAATG |
|
||
Remove ATG from sequence |
3' |
TTCGAGAGACC |
|
||||
C-tag_1 |
FG |
Remove restriction enzymes |
5' |
GGTCTCATTCGgc |
Reading frame |
||
Remove ATG from sequence |
3' |
GCTTAGAGACC |
|
||||
C-tag_2 |
GH |
Remove restriction enzymes |
5' |
GGTCTCATTCGcg |
Reading frame |
||
Remove ATG from sequence |
3' |
GGTAAGAGACC |
|
||||
Terminator |
HI |
Remove restriction enzymes |
5' |
GGTCTCAGGTA |
|
||
|
3' |
CGCTAGAGACC |
|
||||
1 x N-Tag + 1x C-Tag |
Promoter |
AB |
Remove restriction enzymes |
5' |
GGTCTCAGGAG |
|
|
|
3' |
TACTAGAGACC |
|
||||
RBS |
BC |
Remove restriction enzymes |
5' |
GGTCTCATACT |
Distance to ATG |
||
|
3' |
CCATAGAGACC |
|
||||
N-tag_1 |
CD |
Remove restriction enzymes |
5' |
GGTCTCACCATg |
Reading frame |
||
Remove ATG from sequence |
3' |
gcAATGAGAGACC |
|
||||
CDS |
DF |
Remove restriction enzymes |
5' |
GGTCTCAAATG |
|
||
Remove ATG from sequence |
3' |
TTCGAGAGACC |
|
||||
Remove stop codon |
|
|
|
||||
C-tag_1 |
FG |
Remove restriction enzymes |
5' |
GGTCTCATTCGgc |
Reading frame |
||
Remove ATG from sequence |
3' |
GCTTAGAGACC |
|
||||
Terminator |
GI |
Remove restriction enzymes |
5' |
GGTCTCAGCTT |
|
||
3' |
CGCTAGAGACC |
|
|||||
2x N-tags + 1 C-tag |
Promoter |
AB |
Remove restriction enzymes |
5' |
GGTCTCAGGAG |
|
|
|
3' |
TACTAGAGACC |
|
||||
RBS |
BC |
Remove restriction enzymes |
5' |
GGTCTCATACT |
Distance to ATG |
||
|
3' |
CCATAGAGACC |
|
||||
N-tag_1 |
CD |
Remove restriction enzymes |
5' |
GGTCTCACCATg |
Reading frame |
||
Remove ATG from sequence |
3' |
gcAATGAGAGACC |
|
||||
N-tag_2 |
DE |
Remove restriction enzymes |
5' |
GGTCTCAAATG |
Reading frame |
||
Remove ATG from sequence |
3' |
tcAGGTAGAGACC |
|
||||
CDS |
EF |
Remove restriction enzymes |
5' |
GGTCTCAAGGTcg |
|
||
Remove ATG from sequence |
3' |
TTCGAGAGACC |
|
||||
C-tag_1 |
FG |
Remove restriction enzymes |
5' |
GGTCTCATTCGgc |
Reading frame |
||
Remove ATG from sequence |
3' |
GCTTAGAGACC |
|
||||
Terminator |
GI |
Remove restriction enzymes |
5' |
GGTCTCAGCTT |
|
||
3' |
CGCTAGAGACC |
|
|||||
1 x N-Tag + 2 x C-Tag |
Promoter |
AB |
Remove restriction enzymes |
5' |
GGTCTCAGGAG |
|
|
3' |
TACTAGAGACC |
|
|||||
RBS |
BC |
Remove restriction enzymes |
5' |
GGTCTCATACT |
Distance to ATG |
||
3' |
CCATAGAGACC |
|
|||||
N-tag_1 |
CD |
Remove restriction enzymes |
5' |
GGTCTCACCATg |
Reading frame |
||
Remove ATG from sequence |
3' |
gcAATGAGAGACC |
|
||||
CDS |
DF |
Remove restriction enzymes |
5' |
GGTCTCAAATG |
|
||
Remove ATG from sequence |
3' |
TTCGAGAGACC |
|
||||
Remove stop codon |
|
|
|
||||
C-tag_1 |
FG |
Remove restriction enzymes |
5' |
GGTCTCATTCGgc |
Reading frame |
||
Remove ATG from sequence |
3' |
GCTTAGAGACC |
|
||||
C-tag_2 |
GH |
Remove restriction enzymes |
5' |
GGTCTCAGCTTcg |
Reading frame |
||
Remove ATG from sequence |
3' |
GGTAAGAGACC |
|
||||
Terminator |
HI |
Remove restriction enzymes |
5' |
GGTCTCAGGTA |
|
||
3' |
CGCTAGAGACC |
|
|||||
2 x N-Tag + 2 x C-Tag |
Promoter |
AB |
Remove restriction enzymes |
5' |
GGTCTCAGGAG |
|
|
3' |
TACTAGAGACC |
|
|||||
RBS |
BC |
Remove restriction enzymes |
5' |
GGTCTCATACT |
Distance to ATG |
||
3' |
CCATAGAGACC |
|
|||||
N-tag_1 |
CD |
Remove restriction enzymes |
5' |
GGTCTCACCATg |
Reading frame |
||
Remove ATG from sequence |
3' |
gcAATGAGAGACC |
|
||||
N-tag_2 |
DE |
Remove restriction enzymes |
5' |
GGTCTCAAATG |
Reading frame |
||
Remove ATG from sequence |
3' |
tcAGGTAGAGACC |
|
||||
CDS |
EF |
Remove restriction enzymes |
5' |
GGTCTCAAGGTcg |
|
||
Remove ATG from sequence |
3' |
TTCGAGAGACC |
|
||||
Remove stop codon |
|
|
|
||||
C-tag_1 |
FG |
Remove restriction enzymes |
5' |
GGTCTCATTCGgc |
Reading frame |
||
Remove ATG from sequence |
3' |
GCTTAGAGACC |
|
||||
C-tag_2 |
GH |
Remove restriction enzymes |
5' |
GGTCTCAGCTTcg |
Reading frame |
||
Remove ATG from sequence |
3' |
GGTAAGAGACC |
|
||||
Terminator |
HI |
Remove restriction enzymes |
5' |
GGTCTCAGGTA |
|
||
3' |
CGCTAGAGACC |
|
Once, the sequence is corrected, it can be included in the system.
Click the combo-box and select “Custom part”. A pop up window is opened and it can be fill with the custom name, the sequence or the size of the sequence and the concentration. The following figure shows the case where the cds is selected.
b) Click on Submit button to save the changes.
After the selection of all parts, the final information related to final concentration, enzyme requirements, required water and buffer quantity can be calculated clicking on the button “Calculate set-up“
The construction can be stored as genbank format clicking on the Download Genbank Button, or can be viewed by the viewer tool or it can be set up.
The concentrations and sequence lengths form the assembly are used to calculate the final protocol parameters. The Golden Gate Wizard tool send the information to Golden Gate Setup module and redirect to Golden Standard Setup page.
A table with the information introduced previously appear, with the final calculations. The results can be easily edited clicking on the squares. Initially, the concentrations are empty and it is necessary to fill them to have final concentrations instead infinity values. In the upper part of the table the total amount of volume or the number of desired fmol can be modified if the user needs.
After the calculation is done, this table can be printed using the button Print.
To store the construction, it can be downloaded clicking the Export button.
The server will redirect to the vector viewer (Open-vector-editor)
showing the final construction. By default Single cutters restriction sites are activated, but to show the restriction sites of the enzymes used in Golden Standard it can be activated Clicking on .
A menu will open with the activated enzymes. And to include others, clicking on the top-right triangle a list of them will be shown.
GoldenStandard can be selected and it will be included into the activated enzymes.
To download the construction in Genbank format, it is necessary click on Download genbank button.