Journal Article

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

Yang, Yanfang, Sun, Guiling, Wilson, Iain W, Guo, Guangwu, Liu, Hongwei, Bellgard, Matthew I, Zhao, Hainan, Tang, Qi, Chen, Li, Lai, Jinsheng, Walker, Kevin D, Parks, Joshua W, Barrero, Roberto A, Huang, Xin, Xie, Fuliang, Hoffman, Angela, Zhang, Baohong, Qiu, Deyou, Bruce, Robert, Zhang, Yong

2014

Overview

Background Paclitaxel (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. Results The 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. Conclusions Our 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.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Acyltransferases - classification / Acyltransferases - genetics / Acyltransferases - metabolism / Animal Genetics and Genomics / Base Sequence / Bioinformatics / Biomedical and Life Sciences / Biosynthesis / Chromatography, High Pressure Liquid / Comparative and evolutionary genomics / Corylus avellana / Farnesyltranstransferase - classification / Farnesyltranstransferase - genetics / Farnesyltranstransferase - metabolism / Fungal Proteins - classification / Fungal Proteins - genetics / Fungal Proteins - metabolism / Fungi / Fungi - genetics / Gene Transfer, Horizontal / Genes / Genome, Fungal / Genomes / Genomics / Industrial production / Life Sciences / Liquid chromatography / Mass Spectrometry / Maximum likelihood method / Microarrays / Microbial Genetics and Genomics / Mixed Function Oxygenases - classification / Mixed Function Oxygenases - genetics / Mixed Function Oxygenases - metabolism / Mode of action / Molecular Sequence Data / NMR / Nuclear magnetic resonance / Paclitaxel - analysis / Paclitaxel - biosynthesis / Penicillium - classification / Penicillium - genetics / Penicillium aurantiogriseum / Phylogenetics / Phylogeny / Plant Genetics and Genomics / Proteins / Proteomics / Research Article / Sequence Analysis, RNA / Studies / Taxus / Trees