Herbicidal nucleosides from microbial sources.

Isaac, Barbara G.; Ayer, Stephen W.; Letendre, Leo J.; Stonard, Richard J.

doi:10.7164/antibiotics.44.729

Cited by 40 publications

(22 citation statements)

References 7 publications

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“…The molecules in which they are found range from cofactors involved in the biosynthesis of tetracycline antibiotics (McCormick and Morton, 1982; Miller et al, 1960) and DNA repair (Kuo et al, 1989) to compounds with herbicidal, antibacterial, antifungal and antineoplastic activities (Isaac et al, 1991; Nishioka et al, 1991; Suhadolnik, 1970a). The breadth of structural diversity in deazapurine-containing family of compounds is remarkable (Figure 1a).…”

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confidence: 99%

Deciphering Deazapurine Biosynthesis: Pathway for Pyrrolopyrimidine Nucleosides Toyocamycin and Sangivamycin

McCarty

Bandarian

2008

Chemistry & Biology

104

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Summary Pyrrolopyrimidine nucleosides analogs, collectively referred to as deazapurines, are an important class of structurally diverse compounds found in a wide variety of biological niches. In this report, a cluster of genes from Streptomyces rimosus involved in production of the deazapurine antibiotics sangivamycin and toyocamycin was identified using forward genetics methods. The cluster includes toyocamycin nitrile hydratase, an enzyme that catalyzes the conversion of toyocamycin to sangivamycin. In addition to this rare nitrile hydratase, the cluster encodes a GTP cyclohydrolase I, linking the biosynthesis of deazapurines to folate biosynthesis, and a set of purine salvage genes, which presumably convert the guanine moiety from GTP to the adenine-like deazapurine base found in toyocamycin and sangivamycin. The gene cluster presented here could potentially serve as a “Rosetta stone” to inform on deazapurine biosynthesis in other bacterial species.

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confidence: 99%

Deciphering Deazapurine Biosynthesis: Pathway for Pyrrolopyrimidine Nucleosides Toyocamycin and Sangivamycin

McCarty

Bandarian

2008

Chemistry & Biology

104

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“…Embryonic factor 1 (FAC1) 5 was recently identified as one of the earliest expressed plant genes and is essential for the zygote to embryo transition in Arabidopsis thaliana (1). The zygote-lethal phenotype is characterized by developmental arrest at the 8 -16-cell stage and mutant embryo shriveling 2-3 days after fertilization.…”

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confidence: 99%

“…Exposure to carbocyclic coformycin results in cessation of seedling growth, followed by paling and necrosis at the apical meristem (3). Coformycin, a structurally related compound produced by a number of microbes (4,5), also has herbicidal properties (5). Although the intracellular metabolism of this compound in plants has not been examined, its mode of action is presumably similar because coformycin 5Ј-phosphate is a transition state inhibitor of rabbit muscle AMPD (6).…”

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confidence: 99%

Membrane Association, Mechanism of Action, and Structure of Arabidopsis Embryonic Factor 1 (FAC1)

Han

Bingman

Mahnke

et al. 2006

Journal of Biological Chemistry

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Embryonic factor 1 (FAC1) is one of the earliest expressed plant genes and encodes an AMP deaminase (AMPD), which is also an identified herbicide target. This report identifies an N-terminal transmembrane domain in Arabidopsis FAC1, explores subcellular fractionation, and presents a 3.3-Å globular catalytic domain x-ray crystal structure with a bound herbicide-based transition state inhibitor that provides the first glimpse of a complete AMPD active site. FAC1 contains an (␣/␤) 8 -barrel characterized by loops in place of strands 5 and 6 that places it in a small subset of the amidohydrolase superfamily with imperfect folds. Unlike tetrameric animal orthologs, FAC1 is a dimer and each subunit contains an exposed Walker A motif that may be involved in the dramatic combined K m (25-80-fold lower) and V max (5-6-fold higher) activation by ATP. Normal mode analysis predicts a hinge motion that flattens basic surfaces on each monomer that flank the dimer interface, which suggests a reversible association between the FAC1 globular catalytic domain and intracellular membranes, with N-terminal transmembrane and disordered linker regions serving as the anchor and attachment to the globular catalytic domain, respectively.Embryonic factor 1 (FAC1) 5 was recently identified as one of the earliest expressed plant genes and is essential for the zygote to embryo transition in Arabidopsis thaliana (1). The zygote-lethal phenotype is characterized by developmental arrest at the 8 -16-cell stage and mutant embryo shriveling 2-3 days after fertilization. The Arabidopsis FAC1 locus encodes an AMP deaminase (AMPD; EC 3.5.4.6), which is a eukaryotic enzyme that catalyzes the hydrolytic deamination of AMP to IMP. AMPD has also been identified as the intracellular target for a class of herbicides that are produced by fungal pathogens. Carbocyclic coformycin was initially discovered in Saccharothrix (2), and plant cells can take up this diffusible nucleoside and 5Ј-phosphorylate it to produce a potent transition state inhibitor of AMPD (3). Exposure to carbocyclic coformycin results in cessation of seedling growth, followed by paling and necrosis at the apical meristem (3). Coformycin, a structurally related compound produced by a number of microbes (4, 5), also has herbicidal properties (5). Although the intracellular metabolism of this compound in plants has not been examined, its mode of action is presumably similar because coformycin 5Ј-phosphate is a transition state inhibitor of rabbit muscle AMPD (6). Both herbicides are inhibitors of mammalian adenosine deaminase (ADA) (3, 6), but the lack of this enzyme in plants (3, 7-9) supports the argument that AMPD is the intracellular target for their nucleotide derivatives. Taken together, these observations suggest that AMPD is essential throughout the plant life cycle. However, the underlying basis for lethality of a FAC1 null phenotype and for herbicidal toxicity related to the catalytic inhibition of this enzyme is not known.AMPD catalyzes the initial step in adenine to guanine ribon...

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“…Coformycin (Isaac et al, 1991) produced by various microbes and carbocyclic coformycin (Bush et al, 1993) isolated from a fermentation of Saccharothrix spp. have previously been reported to have herbicidal activity.…”

Section: Research For Finding New Target Sitesmentioning

confidence: 99%

Molecular Mechanism of Action of Herbicides

Jablonkai¹

2011

Herbicides - Mechanisms and Mode of Action

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Herbicidal nucleosides from microbial sources.

Cited by 40 publications

References 7 publications

Deciphering Deazapurine Biosynthesis: Pathway for Pyrrolopyrimidine Nucleosides Toyocamycin and Sangivamycin

Deciphering Deazapurine Biosynthesis: Pathway for Pyrrolopyrimidine Nucleosides Toyocamycin and Sangivamycin

Membrane Association, Mechanism of Action, and Structure of Arabidopsis Embryonic Factor 1 (FAC1)

Molecular Mechanism of Action of Herbicides

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