meleagrin and neoxaline

The biosynthesis of secondary metabolites in fungi is catalyzed by enzymes encoded by genes linked in clusters that are frequently co-regulated at the transcriptional level. Formation of gene clusters may take place by de novo assembly of genes recruited from other cellular functions, but also novel gene clusters are formed by reorganization of progenitor clusters and are distributed by horizontal gene transfer. This article reviews (i) the published information on the roquefortine/meleagrin/neoxaline gene clusters of Penicillium chrysogenum (Penicillium rubens) and the short roquefortine cluster of Penicillium roqueforti, and (ii) the correlation of the genes present in those clusters with the enzymes and metabolites derived from these pathways. The P. chrysogenum roq/mel cluster consists of seven genes and includes a gene (roqT) encoding a 12-TMS transporter protein of the MFS family. Interestingly, the orthologous P. roquefortine gene cluster has only four genes and the roqT gene is present as a residual pseudogene that encodes only small peptides. Two of the genes present in the central region of the P. chrysogenum roq/mel cluster have been lost during the evolutionary formation of the short cluster and the order of the structural genes in the cluster has been rearranged. The two lost genes encode a N1 atom hydroxylase (nox) and a roquefortine scaffold-reorganizing oxygenase (sro). As a consequence P. roqueforti has lost the ability to convert the roquefortine-type carbon skeleton to the glandicoline/meleagrin-type scaffold and is unable to produce glandicoline B, meleagrin and neoxaline. The loss of this genetic information is not recent and occurred probably millions of years ago when a progenitor Penicillium strain got adapted to life in a few rich habitats such as cheese, fermented cereal grains or silage. P. roqueforti may be considered as a "domesticated" variant of a progenitor common to contemporary P. chrysogenum and related Penicillia.

Topics: Alkaloids; Evolution, Molecular; Gene Rearrangement; Heterocyclic Compounds, 4 or More Rings; Indoles; Metabolic Networks and Pathways; Multigene Family; Ovomucin; Penicillium; Piperazines

Three strains of each of the seven taxa comprising the Penicillium series Corymbifera were surveyed by direct injection mass spectrometry (MS) and liquid chromatography-MS for the production of terrestric acid and roquefortine/oxaline biosynthesis pathway metabolites when cultured upon macerated tissue agars prepared from Allium cepa, Zingiber officinale, and Tulipa gesneriana, and on the defined medium Czapek yeast autolysate agar (CYA). A novel solid-phase extraction methodology was applied for the rapid purification of roquefortine metabolites from a complex matrix. Penicillium hordei and P. venetum produced roquefortine D and C, whereas P. hirsutum produced roquefortine D and C and glandicolines A and B. P. albocoremium, P. allii, and P. radicicola carried the pathway through to meleagrin, producing roquefortine D and C, glandicolines A and B, and meleagrin. P. tulipae produced all previously mentioned metabolites yet carried the pathway through to an end product recognized as epi-neoxaline, prompting the proposal of a roquefortine/epi-neoxaline biogenesis pathway. Terrestric acid production was stimulated by all Corymbifera strains on plant-derived media compared to CYA controls. In planta, production of terrestric acid, roquefortine C, glandicolines A and B, meleagrin, epi-neoxaline, and several other species-related secondary metabolites were confirmed from A. cepa bulbs infected with Corymbifera strains. The deposition of roquefortine/oxaline pathway metabolites as an extracellular nitrogen reserve for uptake and metabolism into growing mycelia and the synergistic role of terrestric acid and other Corymbifera secondary metabolites in enhancing the competitive fitness of Corymbifera species in planta are proposed.

Topics: Absidia; Alkaloids; Canada; Gas Chromatography-Mass Spectrometry; Heterocyclic Compounds, 4 or More Rings; Imidazoles; Indoles; Ovomucin; Penicillium; Piperazines; Plant Roots; Species Specificity