title: Screening marine fungi for inhibitors of the C4 plant enzyme pyruvate phosphate dikinase: unguinol as a potential novel herbicide candidate.
abstract: 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.
authors.affiliation: Australian Institute of Marine Science, PMB 3, Townsville, Queensland, Australia 4810. c.motti@aims.gov.au
authors.forename: Cherie A
authors.initials: CA
authors.lastname: Motti
authors.forename: David G
authors.initials: DG
authors.lastname: Bourne
authors.forename: James N
authors.initials: JN
authors.lastname: Burnell
authors.forename: Jason R
authors.initials: JR
authors.lastname: Doyle
authors.forename: Dianne S
authors.initials: DS
authors.lastname: Haines
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Liptrot
authors.forename: Lyndon E
authors.initials: LE
authors.lastname: Llewellyn
authors.forename: Shilo
authors.initials: S
authors.lastname: Ludke
authors.forename: Andrew
authors.initials: A
authors.lastname: Muirhead
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Tapiolas
mesh_terms: 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
chemical_list: 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