Table 1.
Mutations identified in more than one GNF179-resistant S. cerevisiae line, from a pool of 13 evolved strains.
| Standard and systematic gene name | Strain/clone name | Amino acid change | GNF179 IC50 (µM) | GNF179-fold resistance (FR) |
|---|---|---|---|---|
| N/A | ABC16-Monster-Parent | N/A | 45.39 ± 5.7 | N/A |
| ELO2 (YCR034W) Fatty acid elongase, involved in sphingolipid biosynthesis | GNF179-R9-2 | G183C | 81.18 + 6.3 | 1.8 |
| GNF179-R10-2 | G183C | 90.31 ± 14.8 | 2.0 | |
| GNF179-R18g1 | L193W | 137.66 ± 5.1 | 3.0 | |
| GNF179-R8h2 | L169R | 138.05a | 3.0 | |
| GNF179-R9f2 | A186D | 94.7 ± 41.3 | 2.1 | |
| SUR2 (YDR297W) Sphingosine C4-hydroxylase | GNF179-R18g1 | S94* | 137.66 ± 5.1 | 3.0 |
| GNF179-R19g2 | D257Y | 109.35 ± 23.1 | 2.4 | |
| GNF179-R9f2 | I108K | 94.7 ± 41.3 | 2.1 | |
| ATG15(YCR068W) Phospholipase | GNF179-R18g1 | W200* | 137.66 ± 5.1 | 3.0 |
| GNF179-R19g2 | C271Y | 109.35 ± 23.1 | 2.4 | |
| GNF179-R9f2 | W380* | 94.7 ± 41.3 | 2.1 | |
| GNF179-R8h2 | K303fs | 138.05a | 3.0 | |
| LCB4 (YOR171C) Sphingoid long-chain base kinase | GNF179-R9f2 | Y421N/A423S | 94.7 ± 41.3 | 2.1 |
| GNF179-R8h2 | T336K | 138.05a | 3.0 | |
| YMR102C Protein of unknown function | GNF179-R19g2 | S448W | 109.35 ± 23.1 | 2.4 |
| GNF179-R9f2 | F381V | 94.7 ± 41.3 | 2.1 | |
| GNF179-R18g1 | L271fs | 137.66 ± 5.1 | 3.0 | |
| GNF179-R8h2 | Q98fs | 138.05a | 3.0 | |
| SEC66 (YBR171W) | GNF179-R1-2 | S107* | 80.12 ± 14.6 | 1.8 |
| Non-essential subunit of Sec63 complex | GNF179-R12-2 | M1I | 67.22 ± 10.4 | 1.5 |
Eighteen hours IC50s against GNF179 (mean ± standard error with n ≥ 2) and fold resistances (calculated relative to the parental ABC16-Monster-Parent strain) are indicated. The complete set of coding changes for the 13 resistant lines are given in Supplementary Data 1.
aReplicate not available.