Genome sequencing and analysis of the paclitaxel-producing endophytic fungus Penicillium aurantiogriseum NRRL 62431

Abstract

BackgroundPaclitaxel (Taxol™) is an important anticancer drug with a unique mode of action. The biosynthesis of paclitaxel had been considered restricted to the Taxus species until it was discovered in Taxomyces andreanae, an endophytic fungus of T. brevifolia. Subsequently, paclitaxel was found in hazel (Corylus avellana L.) and in several other endophytic fungi. The distribution of paclitaxel in plants and endophytic fungi and the reported sequence homology of key genes in paclitaxel biosynthesis between plant and fungi species raises the question about whether the origin of this pathway in these two physically associated groups could have been facilitated by horizontal gene transfer.ResultsThe ability of the endophytic fungus of hazel Penicillium aurantiogriseum NRRL 62431 to independently synthesize paclitaxel was established by liquid chromatography-mass spectrometry and proton nuclear magnetic resonance. The genome of Penicillium aurantiogriseum NRRL 62431 was sequenced and gene candidates that may be involved in paclitaxel biosynthesis were identified by comparison with the 13 known paclitaxel biosynthetic genes in Taxus. We found that paclitaxel biosynthetic gene candidates in P. aurantiogriseum NRRL 62431 have evolved independently and that horizontal gene transfer between this endophytic fungus and its plant host is unlikely.ConclusionsOur findings shed new light on how paclitaxel-producing endophytic fungi synthesize paclitaxel, and will facilitate metabolic engineering for the industrial production of paclitaxel from fungi.

Endophytes as in vitro production platforms of high value plant secondary metabolites

“…This has been well established in the case of gibberellin biosynthetic pathways in fungi and higher plants which show several differences and have evolved independently rather than by HGT (Hedden et al, 2001;Tudzynski, 2005). Similar findings have been reported in case of taxol producing endophytes where the fungal ts and bapt genes have been found to have low similarities to the corresponding plant genes (Xiong et al, 2013;Yang et al, 2014c), which suggests and supports co-evolution theory rather than HGT theory.…”

“…Hence, the authors concluded that fungal taxane was in fact residual plant taxane which, due to its lipophilicity, formed complexes with the endophyte cell wall structures that would persist for up to a few passages of the fungal cultures. However, a very recent study reported by Yang et al (2014c) on the whole genome sequencing of taxol producing endophyte Penicillium aurantiogriseum NRRL 62431 directly contradicts the findings of Heinig et al (2013). When the fungal genome was scanned via multiple sequence alignments for potential paclitaxel biosynthesis genes, putative genes showing low homology with the Taxus genes but with distinct conserved amino acid sites emerged, supporting the independent evolution theory over HGT.…”

An endophyte of Picrorhiza kurroa Royle ex. Benth, producing menthol, phenylethyl alcohol and 3-hydroxypropionic acid, and other volatile organic compounds

“…which were distinct from the plant homologues but used the same mechanism (Shaw et al 2015). Earlier reports also suggest that there is only limited sequence similarity between plant and microbial enzymes/genes (Starks et al 1997;Yang et al 2014). It is interesting to note that PR4 produces menthol independent of its host, Picrorhiza kurroa.…”

Plant Bioactive Metabolites and Drugs Produced by Endophytic Fungi of Spermatophyta

“…Penicillium aurantiogriseum C. avellana [252] Penicillium raistrickii Taxus brevifolia [253] Penicillium sp.…”