- Start an overnight culture of 3357-5 by putting 1-3ml of Triton-X on an older, sporulating plate and scraping the whole plate using a glass spreader bar, add to 100ml of PDBU grow at: 200rpm and 28°C for 12-16hrs, 30°C 10-12h
- The following day freshly prepare the enzyme solution
- Pour the culture into 2 50ml conical tubes
- Centrifuge the overnight culture at “6” for 10 minutes in the clinical centrifuge. (Around 8k RPM in swinging bucket)
- Pour off supernatant and resuspend with sterile water.
- Centrifuge at “6” for 12 minutes in the clinical centrifuge.
- Pour off supernatant
- Filter the enzyme solution using a .45mm filter and add 15ml of the enzyme solution for each 5ml of tissue (each conical tube).
- Shake for 3-4hrs at 70rpm at 30-32°C
- Centrifuge at 200rpm for 1 minute in a swinging bucket rotor or at “2” for 1 minute in the clinical centrifuge.
- Pour the supernatant into a new 50ml conical tube and top off with 50ml of STC buffer, (I prefer to use a 50ml serological pipet to remove the supernatant).
- Centrifuge at 3000rpm for 5 minutes in a swinging bucket rotor or at “4” for 10 minutes in a clinical centrifuge
- Pour off supernatant
- Resuspend in 50ml STC buffer
- Repeat step #12
- Pour off supernatant leaving just a little STC in the bottom of each conical, be careful not to tilt the tube back up to soon or you’ll need to resuspend in STC and spin again.
- Create 1:10 and 1:20 dilutions in STC
- Using the hemocytometer, count the protoplasts present in five of the boxes
- Calculate total number of protoplasts using the formula: protoplasts x dilution x 50,000
- If necessary dilute the protoplasts to1x108/ml, generally I find my concentration to be about 1×107/ml
- Add 100ml of diluted protoplasts to 1.5ml tubes (one with just protoplasts, one with just auxotrophic marker, and the rest with your plasmids)
- Add 1-10mg of each DNA to be transformed
- Mix by gently pipeting up and down
- Incubate on ice for 20 minutes
- Add 1ml of 50% PEG
- Mix by gently pipeting up and down
- Incubate at RT for 20 minutes
- Plate 200-300ml of protoplasts on the surface of recovery media
- MLS+U
- Protoplasts (negative control)
- MLS
- Protoplasts (positive control)
- Stack the plates and incubate at 37°C for 2-4 days.
- Pick colonies using sterile toothpick and transfer to 60mm PDB agar plates, grow 3-4days and isolate DNA using CTAB method if needed to pcr screen for knockout.
Materials and Solutions
PDBU (100ml)
- 2.4g Potato Dextrose Broth
- 0.112g uracil
- 100ml diH2O
Enzyme Solution (30ml to be divided into 2)
- 25.5 ml 1.2MNaCl (7g in 100ml diH2O)
- 3ml 0.2M NaPO4
- 0.14g Lysing enzyme (4°C) Sigma #L-14122
- 0.08g Driselase (-20°C) Sigma #D-9515
- 300ml b-glucorinidase (4°C) Sigma #G-0876
- 0.08g BSA (4°C dry) Sigma #A2153-100G
50% PEG (100ml)
- 50g PEG (MW 4,000)
- 1ml 1M stock TrisCl (pH7.5)
- 1ml 1M stock CaCl2
- Filter sterilize
STC Buffer (500ml)
- 109.32g Sorbitol
- 5ml 1M stock TrisCl (pH7.5)
- 5ml 1M stock CaCl2
- 500ml diH2O
- Autoclave and store at 4°C
MLS (500ml)
- 17.5g Czapeck’s broth
- 26.43g 0.4MNH4SO4
- 5g agar
MLS+U (500ml)
- 17.5g Czapeck’s broth
- 26.43g 0.4MNH4SO4
- 5g agar
- 0.561g uracil