No abstract

Coumarins (1,2-benzopyrones) are ubiquitously found in higher plants where they originate from the phenylpropanoid pathway. They contribute essentially to the persistence of plants being involved in processes such as defense against phytopathogens, response to abiotic stresses, regulation of oxidative stress, and probably hormonal regulation. Despite their importance, major details of their biosynthesis are still largely unknown and many P450-dependent enzymatic steps have remained unresolved. Ortho-hydroxylation of hydroxycinnamic acids is a pivotal step that has received insufficient attention in the literature. This hypothetical P450 reaction is critical for the course for the biosynthesis of simple coumarin, umbelliferone and other hydroxylated coumarins in plants. Multiple P450 enzymes are also involved in furanocoumarin synthesis, a major class of phytoalexins derived from umbelliferone. Several of them have been characterized at the biochemical level but no monooxygenase gene of the furanocoumarin pathway has been identified yet. This review highlights the major steps of the coumarin pathway with emphasis on the cytochrome P450 enzymes involved. Recent progress and the outcomes of novel strategies developed to uncover coumarin-committed CYPs are discussed.

Ammi majus L. accumulates linear furanocoumarins by cytochrome P450 (CYP)-dependent conversion of 6-prenylumbelliferone via (؉)-marmesin to psoralen. Relevant activities, i.e. psoralen synthase, are induced rapidly from negligible background levels upon elicitation of A. majus cultures with transient maxima at 9 -10 h and were recovered in labile microsomes. Expressed sequence tags were cloned from elicited Ammi cells by a nested DD-RT-PCR strategy with CYP-specific primers, and full-size cDNAs were generated from those fragments correlated in abundance with the induction profile of furanocoumarin-specific activities. One of these cDNAs representing a transcript of maximal abundance at 4 h of elicitation was assigned CYP71AJ1. Functional expression in Escherichia coli or yeast cells initially failed but was accomplished eventually in yeast cells after swapping the N-terminal membrane anchor domain with that of CYP73A1. The recombinant enzyme was identified as psoralen synthase with narrow substrate specificity for (؉)-marmesin. Psoralen synthase catalyzes a unique carbon-chain cleavage reaction concomitantly releasing acetone by syn-elimination. Related plants, i.e. Heracleum mantegazzianum, are known to produce both linear and angular furanocoumarins by analogous conversion of 8-prenylumbelliferone via (؉)-columbianetin to angelicin, and it was suggested that angelicin synthase has evolved from psoralen synthase. However, (؉)-columbianetin failed as substrate but competitively inhibited psoralen synthase activity. Analogy modeling and docked solutions defined the conditions for high affinity substrate binding and predicted the minimal requirements to accommodate (؉)-columbianetin in the active site cavity. The studies suggested that several point mutations are necessary to pave the road toward angelicin synthase evolution.Furanocoumarins are produced by many plants, mostly of the Apiaceae, Rutaceae, Moraceae, or the Coronilla and Psoralea genera of the Fabaceae (1-3). Multiple pharmacological effects have been ascribed to several of these metabolites (4 -6), which were included in clinical screenings but received attention also for their inhibitory effect on monooxygenases involved in drug metabolism (7-9) and potential toxicity (10). The (dihydro)furan-substituted 2H-1-benzopyran-2-one forms the characteristic core structure, and the annulation type distinguishes the linear furanocoumarins or psoralens from the angular furanocoumarins (Fig.

This study emphasizes that metformin significantly increases (18)F-FDG uptake in colon and, to a lesser extent, in small intestine. It raises the question of stopping metformin treatment before an (18)F-FDG PET/CT scan is performed for intra-abdominal neoplasic lesion assessment.

BACKGROUND:To prospectively assess fluorodeoxyglucose positron emission tomography/computed

Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands.

SummaryThe spermosphere is the zone surrounding seeds where interactions between the soil, microbial communities and germinating seeds take place. The concept of the spermosphere is usually only applied during germination sensu stricto. Despite the transient nature of this very small zone of soil around the germinating seed, the microbial activities which occur there may have longlasting impacts on plants. The spermosphere is indirectly characterized by either (i) seed exudates, which could be inhibitors or stimulators of microorganism growth or (ii) the composition of the microbiome on and around the germinating seeds. The microbial communities present in the spermosphere directly reflect that of the germination medium or are hostdependent and influenced quantitatively and qualitatively by host exudates. Despite its strong impact on the future development of plants, the spermosphere remains little studied. This can be explained by the technical difficulties related to characterizing this concept due to its short duration, small size and biomass, and the number and complexity of the interactions that take place. However, recent technical methods, such as metabolite profiling, combining phenotypic methods with DNA-and RNA-based methods, could be used to investigate seed exudates, microbial communities and their interactions with the soil environment.

Hybrid FDG-PET-CT is helpful for the detection of a potential head and neck primary tumour. Furthermore, hybrid FDG-PET-CT has the ability to diagnose occult or distant second tumour and metastatic disease and modify patient management.