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Identification of a Polyketide Synthase Gene in the Synthesis of Phleichrome of the Phytopathogenic Fungus Cladosporium phlei
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  • Journal title : Molecules and Cells
  • Volume 38, Issue 12,  2015, pp.1105-1110
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2015.0208
 Title & Authors
Identification of a Polyketide Synthase Gene in the Synthesis of Phleichrome of the Phytopathogenic Fungus Cladosporium phlei
So, Kum-Kang; Chung, Yun-Jo; Kim, Jung-Mi; Kim, Beom-Tae; Park, Seung-Moon; Kim, Dae-Hyuk;
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Phleichrome, a pigment produced by the phytopathogenic fungus Cladosporium phlei, is a fungal perylenequinone whose photodynamic activity has been studied intensively. To determine the biological function of phleichrome and to engineer a strain with enhanced production of phleichrome, we identified the gene responsible for the synthesis of phleichrome. Structural comparison of phleichrome with other fungal perylenequinones suggested that phleichrome is synthesized via polyketide pathway. We recently identified four different polyketide synthase (PKS) genes encompassing three major clades of fungal PKSs that differ with respect to reducing conditions for the polyketide product. Based on in silico analysis of cloned genes, we hypothesized that the non-reducing PKS gene, Cppks1, is involved in phleichrome biosynthesis. Increased accumulation of Cppks1 transcript was observed in response to supplementation with the application of synthetic inducer cyclo-(). In addition, heterologous expression of the Cppks1 gene in Cryphonectria parasitica resulted in the production of phleichrome. These results provide convincing evidence that the Cppks1 gene is responsible for the biosynthesis of phleichrome.
Cladosporium phlei;Cryphonectria parasitica;heterologous expression;phleichrome;polyketide synthase;
 Cited by
Arnone, A., Camarda, L., Nasini, G., and Merlini, L. (1985). Secondary mould metabolites. Part 13. Fungal Perylenequinones: phleichrome, isophleichrome, and their endoperoxides. J. Chem. Soc. Perkin Trans. I 1387-1392.

Baek, J.H., Park, J.A., Kim, J.M., Oh, J.M., Park, S.M., and Kim, D.H. (2014). Functional analysis of a tannic-acid-inducible and hypoviral-regulated small heat-shock protein Hsp24 from the chestnut blight fungus Cryphonectria parasitica. Mol. Plant Microbe Interact. 27, 56-65. crossref(new window)

Chen, R.E., and Thorner, J. (2007). Function and regulation in MAPK signaling pathways:lessons learned from the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta. 1773, 1311-1340. crossref(new window)

Choi, G.H., and Nuss, D.L. (1990). Nucleotide sequence of the glyceraldehyde-3-phosphate dehydrogenase gene from Cryphonectria parasitica. Nucleic Acids Res. 18, 5566. crossref(new window)

Choquer, M., Dekkers, K.L., Chen, H.Q., Cao, L., Ueng, P.P., Daub, M.E., and Chung. K.R. (2005). The CTB1 gene encoding a fungal polyketide synthase is required for cercosporin biosynthesis and fungal virulence of Cercospora nicotianae. Mol. Plant Microbe Interact. 18, 468-476. crossref(new window)

Churchill, A.C.L., Ciufetti, L.M., Hansen, D.R., Van Etten, H.D., and Van Alfen, N.K. (1990). Transformation of the fungal pathogen Cryphonectria parasitica with a variety of heterologous plasmids. Curr. Genet. 17, 25-31 crossref(new window)

Crawford, J.M., and Townsend, C.A. (2010). New insights into the formation of fungal aromatic polyketides. Nat. Rev. Microbiol. 8, 879-889. crossref(new window)

Daub, M.E., and Ehrenshaft, M. (2000). The photoactivated cercospora toxin cercosporin: Contributions to plant disease and fundamental biology. Annu. Rev. Phytopathol. 38, 461-490. crossref(new window)

Daub, M.E., Herrero, S., and Chung, K.R. (2005). Photoactivated perylenequinone toxins in fungal pathogenesis of plants. FEMS Microbiol. Lett. 252, 197-206. crossref(new window)

Du, M., and Maunder, D. (2010). Method for preparing hypocrellin. USA Patent 7816563 B1.

Gehring, A.M., Mori, I., and Walsh, C.T. (1998). The nonribosomal peptide synthetase HMWP2 forms a thiazoline ring during biogenesis of yersiniabactin, an iron-chelating virulence factor of Yersinia pestis. Biochemistry 37, 2648-2659. crossref(new window)

Hudson, J.B., and Towers, G.H. (1991). Therapeutic potential of plant photosensitizers. Pharmacol. Ther. 49, 181-222 crossref(new window)

Hutchinson, C.R., and Fujii, I. (1995). Polyketide synthase gene manipulation-a structure-function approach in engineering novel antibiotics. Annu. Rev. Microbiol. 49, 201-238. crossref(new window)

Kealey, J.T., Liu, L., Santi, D.V., Betlach, M.C., and Barr, P.J. (1998). Production of a polyketide natural product in nonpolyketide-producing prokaryotic and eukaryotic hosts. Proc. Natl. Acad. Sci. USA 95, 505-509. crossref(new window)

Keller, N.P., Turner, G., and Bennett, J.W. (2005). Fungal secondary metabolism-from biochemistry to genomics. Nat. Rev. Microbiol. 3, 937-947. crossref(new window)

Kim, D.H., and Martyn, R,D. (1995). Transformation of Fusarium oxysporum f. sp. niveum to hygromycin B resistance and altered pathogenicity. Mol. Cells 5, 658-667

Kim, J.A., Kim, J.M., Kim, H.G., Kim, B.T., Hwang, K.J., Park, S.M., Yang, M.S., and Kim, D.H. (2009). Protoplast-mediated transformation of the filamentous fungus Cladosporium phlei: Evidence of tandem repeats of the integrative transforming vector. Plant Pathol. J. 25, 179-183. crossref(new window)

Kim, J.M., Song, H.Y., Choi, H.J., So, K.K., Kim, D.H., Chae, K.S., Han, D.M., and Jahng, K.Y. (2015). Characterization of NpgA, a 4-phosphopantetheinyl transferase of Aspergillus nidulans, and evidence of its involvement in fungal growth and formation of conidia and cleistothecia for development. J. Microbiol. 15, 21-32.

Kurobane, I., Vining, L.C., McInnes, A.G., Smith, D.G., and Walter, J.A. (1981). Biosynthesis of elsinochromes C and D. Pattern of acetate incorporation determined by 13C and 2H nmr1. Can. J. Chem. 59, 422-430. crossref(new window)

Kusari, S., Zuhlke, S., Borsch, T., and Spiteller, M. (2009). Positive correlations between hypericin and putative precursors detected in the quantitative secondary metabolite spectrum of Hypericum. Phytochemistry 70, 1222-1232. crossref(new window)

Kwon, B.R., Kim, M.J., Park, J.A., Chung, H.J., Kim, J.M., Park, S.M., Yun, S.H., Yang, M.S., and Kim, D.H. (2009). Assessment of the core cryparin promoter from Cryphonectria parasitica for heterologous expression in filamentous fungi. Appl. Microbiol. Biotechnol. 83, 339-348. crossref(new window)

Lee, J.K., Kim, B.T., Kim, J.A., Chung, H.J., Park, S.M., Yang, M.S., Hwang, K.J., and Kim, D.H. (2007). Cultural characteristics and extraction of the fungal pigment phleichrome from the phytopathogenic fungus Cladosporium phlei. Biotechnol. Bioprocess Eng. 12, 508-515. crossref(new window)

Liao, H.L., and Chung, K.R. (2008). Genetic dissection defines the roles of elsinochrome phytotoxin for fungal pathogenesis and conidiation of the citrus pathogen Elsinoe fawcettii. Mol. Plant Microbe Interact. 21, 469-479. crossref(new window)

Mullaney, E.J., Hamer, J.E., Roberti, K.A., Yelton, M.M., and Timberlake, W.E. (1985). Primary structure of the trpC gene from Aspergillus nidulans. Mol. Gen. Genet. 199, 37-45. crossref(new window)

Nguyen, Q.B., Kadotani, N., Kasahara, S., Tosa, Y., Mayama, S., and Nakayashiki, H. (2008). Systematic functional analysis of calcium-signalling proteins in the genome of the rice-blast fungus, Magnaporthe oryzae, using a high-throughput RNA-silencing system. Mol. Microbiol. 68, 1348-1365. crossref(new window)

Okubo, A., Yamazaki, S., and Fuwa, K. (1975). Biosynthesis of cercosporin. Agric. Biol. Chem. 39, 1173-1175. crossref(new window)

Olivo, M., and Chin, W. (2006). Perylenequinones in photodynamic therapy: cellular versus vascular response. J. Environ. Pathol. Toxicol. Oncol. 25, 223-237. crossref(new window)

Park, S.M., Choi, E.S., Kim, M.J., Cha, B.J., Yang, M.S., and Kim, D.H. (2004). Characterization of HOG1 homologue, CpMK1, from Cryphonectria parasitica and evidence for hypovirusmediated perturbation of its phosphorylation in response to hypertonic stress. Mol. Microbiol. 51, 1267-1277. crossref(new window)

Park, J.A., Kim, J.M., Park, S.M., and Kim, D.H. (2012). Characterization of CpSte11, a MAPKKK gene of Cryphonectria parasitica, and initial evidence of its involvement in the pheromone response pathway. Mol. Plant Pathol. 13, 240-250. crossref(new window)

Quadri, L.E., Sello, J., Keating, T.A., Weinreb, P.H., and Walsh, C.T. (1998). Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chem. Biol. 5, 631-645. crossref(new window)

Shibata, S. (1973). Some recent studies on the metabolites of fungi and lichens. Pure Appl. Chem. 33, 109-128. crossref(new window)

So, K.K., Kim, J.M., Nguyen, N.L., Park, J.A., Kim, B.T., Park, S.M., Hwang, K.J., and Kim, D.H. (2012). Rapid screening of an ordered fosmid library to clone multiple polyketide synthase genes of the phytopathogenic fungus Cladosporium phlei, J. Microbiol. Methods 9, 412-419.

So, K.K., Jo, I.S., Chae, M.S., Kim, J.M., Chung, H.J., Yang, M.S., Kim, B.T., Kim, J.K., Choi, J.K., and Kim, D.H. (2015). Improved production of phleichrome from the phytopathogenic fungus Cladosporium phlei using synthetic inducers and photodynamic ROS production by phleichrome. J. Biosci. Bioeng. 119, 289-296. crossref(new window)

Song, M.Y., Kim, C.Y., Han, M., Ryu, H.S., Lee, S.K., Sun, L., He, Z., Seo, Y.S., Canal, P., Ronald, P.C., and Jeon, J.S. (2013). Differential requirement of Oryza sativa RAR1 in immune receptor-mediated resistanve of rice to Magnaporthe oryzae. Mol. Cells 35, 327-334. crossref(new window)

Walsh, C.T., Gehring, A.M., Weinreb, P.H., Quadri, L.E., and Flugel, R.S. (1997). Post-translational modification of polyketide and nonribosomal peptide synthases. Curr. Opin. Chem. Biol. 1, 309-315. crossref(new window)

Wattanachaisaereekul, S., Lantz, A.E., Nielsen, M.L., Andresson, O.S., and Nielsen, J. (2007). Optimization of heterologous production of the polyketide 6-MSA in Saccharomyces cerevisiae. Biotechnol. Bioeng. 97, 893-900. crossref(new window)

Yi, M.H., Kim, J.A., Kim, J.M., Park, J.A., Kim, B.T., Park, S.M., Yang, M.S., Hwang, K.J., and Kim, D.H. (2011). Characterization of a mutant strain of a filamentous fungus Cladosporium phlei for the mass production of the secondary metabolite phleichrome. J. Microbiol.49, 680-683. crossref(new window)

Yoshihara, T., Shimanuki, T., Araki, T., and Sakamura, S. (1975). Phleichrome, a new phytotoxic compound produced by Cladosporium phlei. Agric. Biol. Chem. 39, 1683-1684. crossref(new window)