Screening marine fungi for inhibitors of the C4 plant enzyme pyruvate phosphate dikinase: unguinol as a potential novel herbicide candidate.
A total of 2,245 extracts, derived from 449 marine fungi cultivated in five types of media, were screened against the C(4) plant enzyme pyruvate phosphate dikinase (PPDK), a potential herbicide target. Extracts from several fungal isolates selectively inhibited PPDK. Bioassay-guided fractionation of one isolate led to the isolation of the known compound unguinol, which inhibited PPDK with a 50% inhibitory concentration of 42.3 +/- 0.8 muM. Further kinetic analysis revealed that unguinol was a mixed noncompetitive inhibitor of PPDK with respect to the substrates pyruvate and ATP and an uncompetitive inhibitor of PPDK with respect to phosphate. Unguinol had deleterious effects on a model C(4) plant but no effect on a model C(3) plant. These results indicate that unguinol inhibits PPDK via a novel mechanism of action which also translates to an herbicidal effect on whole plants.
Motti
Cherie A
CA
Australian Institute of Marine Science, PMB 3, Townsville, Queensland, Australia 4810. c.motti@aims.gov.au
Bourne
David G
DG
Burnell
James N
JN
Doyle
Jason R
JR
Haines
Dianne S
DS
Liptrot
Catherine H
CH
Llewellyn
Lyndon E
LE
Ludke
Shilo
S
Muirhead
Andrew
A
Tapiolas
Dianne M
DM
D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000737:chemistry / Q000235:genetics; D031746:Digitaria / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D005658:Fungi / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D006540:Herbicides / Q000302:isolation & purification* / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000302:isolation & purification* / Q000494:pharmacology*; D001467:Hordeum / Q000187:drug effects; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011772:Pyruvate, Orthophosphate Dikinase / Q000037:antagonists & inhibitors*; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D017422:Sequence Analysis, DNA
D004271:DNA, Fungal; D004275:DNA, Ribosomal; D021903:DNA, Ribosomal Spacer; D004791:Enzyme Inhibitors; D006540:Herbicides; D006575:Heterocyclic Compounds, 3-Ring; D012337:RNA, Ribosomal, 18S; C523064:unguinol; D011772:Pyruvate, Orthophosphate Dikinase