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Open Access Research article

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

Yanfang Yang1, Hainan Zhao2, Roberto A Barrero3, Baohong Zhang4, Guiling Sun56, Iain W Wilson7, Fuliang Xie4, Kevin D Walker8, Joshua W Parks9, Robert Bruce9, Guangwu Guo10, Li Chen10, Yong Zhang11, Xin Huang12, Qi Tang13, Hongwei Liu1, Matthew I Bellgard3, Deyou Qiu1*, Jinsheng Lai2* and Angela Hoffman9*

Author Affiliations

1 State Key Laboratory of Tree Genetics and Breeding, The Research Institute of Forestry, Chinese Academy of Forestry, Beijing 100091, China

2 College of Agricultural Biotechnology, China Agriculture University, Beijing 100094, China

3 Centre for Comparative Genomics, Murdoch University, Perth, WA 6150, Australia

4 Department of Biology, East Carolina University, Greenville, NC 27858, USA

5 School of Life Sciences, Southwest Forestry University, Kunming 650224, China

6 Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China

7 CSIRO Plant Industry, Canberra ACT 2001, Australia

8 Department of Chemistry and Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA

9 Department of Chemistry, University of Portland, Portland, OR 97203, USA

10 BGI-Shenzhen, Shenzhen 518000, China

11 Department of Plant Pathology, China Agricultural University, Beijing 100094, China

12 Institute of Plant Quarantine, Chinese Academy of Inspection and Quarantine, Beijing 100029, China

13 Hunan Provincial Key Laboratory of Crop Germplasm Innovation and Utilization and National Chinese Medicinal Herbs (hunan) Technology Center, Hunan Agricultural University, Changsha 410128, China

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BMC Genomics 2014, 15:69  doi:10.1186/1471-2164-15-69

Published: 25 January 2014

Abstract

Background

Paclitaxel (Taxolâ„¢) 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.

Keywords:
Penicillium aurantiogriseum NRRL 62431; Paclitaxel; Taxolâ„¢; Endophytic fungi; Genome sequence; Horizontal gene transfer