Table 1 Mutations identified in more than one GNF179-resistant S. cerevisiae line, from a pool of 13 evolved strains.

From: Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway

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

  1. 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.
  2. aReplicate not available.