Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids aphelandrine and orantine in Aphelandra sp.

Nezbedová, Lenka; Hesse, Manfred; Drandarov, Konstantin; Bigler, Laurent; Werner, Christa

doi:10.1007/s004250000516

Cited by 13 publications

(5 citation statements)

References 28 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of the reaction leading to the tetraazaperylenehexaone 8 most likely involves oxidative phenolic coupling of the radical species 9 and 10, followed by a four-electron oxidation (Scheme 4). Oxidative C-C coupling reactions of phenols are well-known processes that are usually catalyzed by metals (typically copper), [8][9][10] dicopper-dioxygen complexes, 11 enzymes, 10,12,13 or various reactive oxygen species. 14 In the present case the oxidant is unidentified.…”

Section: Resultsmentioning

confidence: 99%

A Novel Lumazine Synthase Inhibitor Derived from Oxidation of 1,3,6,8-Tetrahydroxy-2,7-naphthyridine to a Tetraazaperylenehexaone Derivative

et al. 2007

View full text Add to dashboard Cite

Air oxidation of 1, 3,6,8-tetrahydroxy-2,7-naphthyridine afforded 2,5,8,11-tetraaza-5,11-dihydro-4,10-dihydroxyperylene-1,3,6,7,9,12-hexaone. X-Ray crystallography of the product revealed that it exists in the meso form in the solid state. The mechanism of product formation most likely involves oxidative phenolic coupling and oxidation. The product proved to be a competitive inhibitor of Schizosaccharomyces pombe lumazine synthase with a K i of 66 ± 13 μM in Tris buffer and 22 ± 4 μM in phosphate buffer. This is significantly more potent than the reactant (K i 350 ± 76 μM, competitive inhibition), which had previously been identified as a lumazine synthase inhibitor by high-throughput screening. Ab initio calculations indicate that the meso form is slightly less stable than the enantiomeric form, and that the two forms interconvert rapidly at room temperature.

show abstract

Section: Resultsmentioning

confidence: 99%

A Novel Lumazine Synthase Inhibitor Derived from Oxidation of 1,3,6,8-Tetrahydroxy-2,7-naphthyridine to a Tetraazaperylenehexaone Derivative

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The formation of carbon–carbon bonds typically requires substrate activation as seen in the reaction mechanisms of PKSs and fatty acid synthases (FAS), where the individual acetyl‐CoA units are activated by carboxylation (Fujii et al ., 2001). However, Barton and Cohen (1957) proposed that new C‐C bonds can be formed by the pairing of radicals produced by one‐electron oxidation of phenols, a process which can be catalysed by laccases (Nezbedová et al ., 2001). A laccase could catalyse the removal of an electron from the deprotonated C 5 ‐OH or C 6 ‐OH groups of nor‐rubrofusarin, rubrofusarin or 9‐hydroxyrubrofusarin to activate the molecules (Fig.…”

Section: Discussionmentioning

confidence: 99%

The biosynthetic pathway for aurofusarin in Fusarium graminearum reveals a close link between the naphthoquinones and naphthopyrones

Frandsen¹,

Nielsen²,

Maolanon³

et al. 2006

Molecular Microbiology

171

187

View full text Add to dashboard Cite

SummaryFungal polyketide biosynthesis typically involves multiple enzymatic steps and the encoding genes are often found in gene clusters. A gene cluster containing PKS12, the polyketide synthase gene responsible for the synthesis of the pigment aurofusarin, was analysed by gene replacement using Agrobacterium tumefaciens-mediated transformation to determine the biosynthesis pathway of aurofusarin. Replacement of aurR1 with hygB shows that it encodes a positively acting transcription factor that is required for the full expression of PKS12, aurJ, aurF, gip1 and FG02329.1, which belong to the gene cluster. AurR1 and PKS12 deletion mutants are unable to produce aurofusarin and rubrofusarin. Bio-and chemoinformatics combined with chemical analysis of replacement mutants (DaurJ, DaurF, Dgip1, DaurO and DPKS12) indicate a five-step enzyme catalysed pathway for the biosynthesis of aurofusarin, with rubrofusarin as an intermediate. This links the biosynthesis of naphthopyrones and naphthoquinones together. Replacement of the putative transcription factor aurR2 results in an increased level of rubrofusarin relative to aurofusarin. Gip1, a putative laccase, is proposed to be responsible for the dimerization of two oxidized rubrofusarin molecules resulting in the formation of aurofusarin.

show abstract

“…Intramolecular cyclization through phenol-oxidative coupling between the phenolic rings of two p-coumaroyl substitutes in bis-(p-coumaroyl) polyamines is the biosynthetic mechanism leading to cyclic alkaloids such as lunarine (in Lunaria annua seeds) and aphelandrine (in Aphelandra sp. roots) [129,130]. The introduction of phenolic rings through aromatic acylation allows, thus, further structural diversification through oxidative coupling.…”

Section: Diversity Of Decorationsmentioning

confidence: 99%

Origin and Function of Structural Diversity in the Plant Specialized Metabolome

Desmet

Morreel

Dauwe

2021

Plants

View full text Add to dashboard Cite

The plant specialized metabolome consists of a multitude of structurally and functionally diverse metabolites, variable from species to species. The specialized metabolites play roles in the response to environmental changes and abiotic or biotic stresses, as well as in plant growth and development. At its basis, the specialized metabolism is built of four major pathways, each starting from a few distinct primary metabolism precursors, and leading to distinct basic carbon skeleton core structures: polyketides and fatty acid derivatives, terpenoids, alkaloids, and phenolics. Structural diversity in specialized metabolism, however, expands exponentially with each subsequent modification. We review here the major sources of structural variety and question if a specific role can be attributed to each distinct structure. We focus on the influences that various core structures and modifications have on flavonoid antioxidant activity and on the diversity generated by oxidative coupling reactions. We suggest that many oxidative coupling products, triggered by initial radical scavenging, may not have a function in se, but could potentially be enzymatically recycled to effective antioxidants. We further discuss the wide structural variety created by multiple decorations (glycosylations, acylations, prenylations), the formation of high-molecular weight conjugates and polyesters, and the plasticity of the specialized metabolism. We draw attention to the need for untargeted methods to identify the complex, multiply decorated and conjugated compounds, in order to study the functioning of the plant specialized metabolome.

show abstract

Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids aphelandrine and orantine in Aphelandra sp.

Cited by 13 publications

References 28 publications

A Novel Lumazine Synthase Inhibitor Derived from Oxidation of 1,3,6,8-Tetrahydroxy-2,7-naphthyridine to a Tetraazaperylenehexaone Derivative

A Novel Lumazine Synthase Inhibitor Derived from Oxidation of 1,3,6,8-Tetrahydroxy-2,7-naphthyridine to a Tetraazaperylenehexaone Derivative

The biosynthetic pathway for aurofusarin in Fusarium graminearum reveals a close link between the naphthoquinones and naphthopyrones

Origin and Function of Structural Diversity in the Plant Specialized Metabolome

Contact Info

Product

Resources

About