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namfest 19191a764c -mushroom-kingdom-fusion-v031[ -mushroom-kingdom-fusion-v031 ][ -mushroom-kingdom-fusion-v031 ][ -mushroom-kingdom-fusion-v031 ]link= -mushroom-kingdom-fusion-v031link= -mushroom-kingdom-fusion-v031link= -mushroom-kingdom-fusion-v031




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Due to the medicinal relevance and unique structure of enfumafungin, the biosynthesis of the compound has been partially investigated (Kuhnert et al. 2018). For this purpose, the genome of producer strain ATCC 74,360 has been sequenced with Illumina technology and assembled into 129 contigs with a total lengths of 32.8 Mbp. Based on its structure enfumafungin was supposed to be derived from a triterpene cyclase with similarity to the lanosterol synthase. The presence of a sugar moiety, acetyl group, hemiacetal and carboxylic acid functionality further indicated that the biosynthetic locus should contain corresponding genes encoding for a glycosyltransferase, acetyltransferase, and multiple oxidative enzymes. Homology searches revealed a biosynthetic gene cluster (BGC) that contained all predicted genes, and which was termed efu. The core gene of the efu biosynthetic gene cluster (efuA) featured a very unusual triterpene cyclase that is fused to a glycosyltransferase Fig. 6. The structure of efuA was verified by cDNA sequencing. Phylogenetic analysis of the terpene synthase demonstrated that EfuA is distinct from known lanosterol synthases and forms an own lineage with homologs from a broad range of organism including bacterial squalene-hopene cyclases and uncharacterized fungal terpene cyclases. The latter are present across the major classes of the fungal kingdom (e.g., Agaricomycetes, Eurotiomycetes, Lecanoromycetes, Sordariomycetes). Most of the homologs did not feature a glycosyltransferase domain, but a subclade in the phylogeny containing EfuA included additional fusion proteins from unrelated fungi indicating that they are not rare (Kuhnert et al. 2018). The frequent occurrence of EfuA homologs in fungi is also in accordance with the structural diversity of glycosylated enfumafungin congeners isolated from various fungal sources. Examples are fuscosatroside from Humicola fuscoatra and Chaetomium sp., peniciside from Penicillium sp., hyalodendrosides from Hyalodendron sp., kolokosides from Xylaria sp. or unglycosylated congeners such as polytolypin from Polytolypa hystricis, and lobarialides and retigeric acids from Lobaria spp. All of these compounds share a common fernane core scaffold (sometimes difficult to recognize due to putative oxidative ring expansions) and are therefore also referred to as fernane-type triterpenoids (see discussion in Kuhnert et al. 2018). 2ff7e9595c


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