Talaromyces atroroseus: Genome sequencing, Monascus pigments and azaphilone gene cluster evolution

Kasper Bøwig Rasmussen

    Research output: Book/ReportPh.D. thesis

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    Monascus pigments have been used for food colouring in Asia for centuries. However, industrially produced Monascus pigments are not approved for use in foods in neither Europe nor the United States. This is partly due to potential risk of co-production of the mycotoxin citrinin by the Monascus species.
    Alternative species for production of Monascus pigments have been described. These are Talaromyces species previously belonging to the Penicillium subgenus Biverticillium but recently transferred to Talaromyces. In the present PhD thesis Talaromyces atroroseus is examined as a suitable Monascus pigment producing organism. As part of the examination, one strain was selected for genome sequencing to unravel the genetic basis for Monascus pigment production in T. atroroseus.
    Talaromyces atroroseus is described as a new species, separated from other Monascus pigment producing Talaromyces species. The taxonomic description is based on multigene phylogenies of ITS, β-tubulin and RPB1. Furthermore T. atroroseus is distinguished from Talaromyces purpurogenus by the lack of production of any known mycotoxins such as the rubratoxins and rugulovasins, which are produced by T. purpurogenus. The lack of mycotoxin production makes T. atroroseus a particular interesting species for a potential industrial pigment production.
    Talaromyces atroroseus IBT11181 was chosen as model-organism for metabolic profiling of produced pigments. It was shown to produce a broad range of red Monascus pigments in reactor-based controlled fermentations. One of these pigments has been structure elucidated and shown to be the glutamine derivative of a known Talaromyces produced Monascus pigment, PP-V.
    Talaromyces atroroseus IBT11181 was full genome sequenced thereby providing the first Talaromyces genome of a suitable Monascus pigment producer. When locating the Monascus pigment gene cluster, it was found that the polyketide synthase (PKS) was missing. Knock-out of the mitorubrin PKS identified this as the PKS delivering the azaphilone backbone to both the group of Monascus pigments as well as the mitorubrins. This form of genetic entanglement of biosynthesis of two groups of secondary metabolites leading to loss of the PKS from one gene cluster is to my knowledge a new observation in the fungal kingdom. This finding indicates that the machinery behind the vast diversity of fungal natural products is much more complex than the genetic machinery, within the normal gene cluster boundaries. By analysis of the Monascus pigment and the mitorubrin gene cluster in Talaromyces I identified five homologous gene pairs to be present in both clusters. Phylogenetic studies of the evolutionary relationship between these gene pairs from the Monascus pigment and the mitorubrin gene cluster in Talaromyces and Monascus give strong evidence that the two clusters originate from a deep segmental duplication of an ancestral azaphilone gene cluster in a common ancestor to Talaromyces, Monascus and Aspergillus lineages. The mitorubrin cluster has since been lost in Monascus, while it has evolved to the azanigerone cluster in Aspergillus niger. In T. atroroseus, the azaphilone PKS from the Monascus pigment gene cluster has since been lost. The loss is probably a result of redundancy in product formation by the two azaphilone PKSs from the Monascus pigment and mitorubrin gene clusters. Utilizing the mitorubrin PKS in production of Monascus pigments might have given the fungus a selective advantage leading to fixation of the Monascus pigment PKS loss.
    Further studies of the mitorubrin gene cluster led to identification of highly homologous gene clusters in genome sequenced Stachybotrys species. Gene-by-gene phylogenies groups several of the Stachybotrys cluster genes adjacent to the Talaromyces mitorubrin cluster genes and within other Eurotiomycetes genes, although the genus Stachybotrys belongs to distant related Sordariomycetes. This phylogenetic study hence gives strong hints towards a horizontal gene transfer of the mitorubrin cluster from a Talaromyces ancestor to a Stachybotrys ancestor.
    It is very valuable that the gene clusters for azaphilones and other pigments are widely found within the fungal kingdom. This gives numerous possibilities to unravel and understand the detailed genetic regulation of pigment production and thereby establishing a sound platform for safe fungal cell factories producing colorants.
    Original languageEnglish
    Number of pages262
    Publication statusPublished - 2015


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