Skip to main content
Log in

A novel polyketide biosynthesis gene cluster is involved in fruiting body morphogenesis in the filamentous fungi Sordaria macrospora and Neurospora crassa

  • Research Article
  • Published:
Current Genetics Aims and scope Submit manuscript

Abstract

During fungal fruiting body development, hyphae aggregate to form multicellular structures that protect and disperse the sexual spores. Analysis of microarray data revealed a gene cluster strongly upregulated during fruiting body development in the ascomycete Sordaria macrospora. Real time PCR analysis showed that the genes from the orthologous cluster in Neurospora crassa are also upregulated during development. The cluster encodes putative polyketide biosynthesis enzymes, including a reducing polyketide synthase. Analysis of knockout strains of a predicted dehydrogenase gene from the cluster showed that mutants in N. crassa and S. macrospora are delayed in fruiting body formation. In addition to the upregulated cluster, the N. crassa genome comprises another cluster containing a polyketide synthase gene, and five additional reducing polyketide synthase (rpks) genes that are not part of clusters. To study the role of these genes in sexual development, expression of the predicted rpks genes in S. macrospora (five genes) and N. crassa (six genes) was analyzed; all but one are upregulated during sexual development. Analysis of knockout strains for the N. crassa rpks genes showed that one of them is essential for fruiting body formation. These data indicate that polyketides produced by RPKSs are involved in sexual development in filamentous ascomycetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  PubMed  CAS  Google Scholar 

  • Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340:783–795

    Article  PubMed  CAS  Google Scholar 

  • Bergmann S, Schümann J, Scherlach K, Lange C, Brakhage AA, Hertweck C (2007) Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3:213–217

    Article  PubMed  CAS  Google Scholar 

  • Bode HB, Müller R (2005) The impact of bacterial genomics on natural product research. Angew Chem Int Ed 44:6828–6846

    Article  CAS  Google Scholar 

  • Bok JW, Keller NP (2004) LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell 3:527–535

    Article  PubMed  CAS  Google Scholar 

  • Bok JW, Noordermeer D, Kale SP, Keller NP (2006) Secondary metabolic gene cluster silencing in Aspergillus nidulans. Mol Microbiol 61:1636–1645

    Article  PubMed  CAS  Google Scholar 

  • Borkovich KA, Alex LA, Yarden O, Freitag M, Turner GE, Read ND, Seiler S, Bell-Pedersen D, Paietta J, Plesofsky N, Plamann M, Goodrich-Tanrikulu M, Schulte U, Mannhaupt G, Nargang FE, Radford A, Selitrennikoff C, Galagan JE, Dunlap JC, Loros JJ, Catcheside D, Inoue H, Aramayo R, Polymenis M, Selker EU, Sachs MS, Marzluf GA, Paulsen I, Davis R, Ebbole DJ, Zelter A, Kalkman ER, O’Rourke R, Bowring F, Yeadon J, Ishii C, Suzuki K, Sakai W, Pratt R (2004) Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. Microbiol Mol Biol Rev 68:1–108

    Article  PubMed  CAS  Google Scholar 

  • Breakspear A, Momany M (2007) The first fifty microarray studies in filamentous fungi. Microbiology 153:7–15

    Article  PubMed  CAS  Google Scholar 

  • Calvo AM, Wilson RA, Bok JW, Keller NP (2002) Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev 66:447–459

    Article  PubMed  CAS  Google Scholar 

  • Colot HV, Park G, Turner GE, Ringelberg C, Crew CM, Litvinkova L, Weiss RL, Borkovich KA, Dunlap JC (2006) A high-throughput gene knockout procedure for Neurospora reveals functions for multiple transcription factors. Proc Nat Acad Sci USA 103:10352–10357

    Article  PubMed  CAS  Google Scholar 

  • Cox RJ (2007) Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. Org Biomol Chem 5:2010–2026

    Article  PubMed  CAS  Google Scholar 

  • Davis RL, deSerres D (1970) Genetic and microbial research techniques for Neurospora crassa. Methods Enzymol 27A:79–143

    Article  Google Scholar 

  • Dean RA, Talbot NJ, Ebbole DJ, Farman ML, Mitchell TK, Orbach MJ, Thon M, Kulkarni R, Xu J-R, Pan H, Read ND, Lee Y-H, Carbone I, Brown D, Oh YY, Donofrio N, Jeong JS, Soanes DM, Djonovic S, Kolomiets E, Rehmeyer C, Li W, Harding M, Kim S, Lebrun M-H, Bohnert H, Coughlan S, Butler J, Calvo S, Ma L-J, Nicol R, Purcell S, Nusbaum C, Galagan JE, Birren BW (2005) The genome sequence of the rice blast fungus Magnaporthe grisea. Nature 434:980–986

    Article  PubMed  CAS  Google Scholar 

  • Dunlap JC, Borkovich KA, Henn MR, Turner GE, Sachs MS, Glass NL, McCluskey K, Plamann M, Galagan JE, Birren BW, Weiss RL, Townsend JP, Loros JJ, Nelson MA, Lambreghts R, Colot HV, Park G, Collopy P, Ringelberg C, Crew C, Litvinkova L, DeCaprio D, Hood HM, Curilla S, Shi M, Crawford M, Koerhsen M, Montgomery P, Larson L, Pearson M, Kasuga T, Tian C, Bastürkmen M, Altamirano L, Xu J (2007) Enabling a community to dissect an organism: overview of the Neurospora functional genomics project. Adv Genet 57:49–96

    Article  PubMed  CAS  Google Scholar 

  • Engh I, Nowrousian M, Kück U (2007) Regulation of melanin biosynthesis via the dihydroxynaphthalene pathway is dependent on sexual development in the ascomycete Sordaria macrospora. FEMS Microbiol Lett 275:62–70

    Article  PubMed  CAS  Google Scholar 

  • Finn RD, Mistry J, Schuster-Bockler B, Griffiths-Jones S, Hollich V, Lassmann T, Moxon S, Marshall M, Khanna A, Durbin R, Eddy SR, Sonnhammer ELL, Bateman A (2006) Pfam: clans, web tools and services. Nucl Acids Res 34:D247–D251

    Article  PubMed  CAS  Google Scholar 

  • Funa N, Awakawa T, Horinouchi S (2007) Pentaketide resorcylic acid synthesis by type III polyketide synthase from Neurospora crassa. J Biol Chem 282:14476–14481

    Article  PubMed  CAS  Google Scholar 

  • Gaffoor I, Brown DW, Plattner R, Proctor RH, Qi W, Trail F (2005) Functional analysis of the polyketide synthase genes in the filamentous fungus Gibberella zeae (anamorph Fusarium graminearum). Eukaryot Cell 4:1926–1933

    Article  PubMed  CAS  Google Scholar 

  • Galagan JE, Calvo SE, Borkovich KA, Selker EU, Read ND, Jaffe D, FitzHugh W, Ma LJ, Smirnov S, Purcell S, Rehman B, Elkins T, Engels R, Wang S, Nielsen CB, Butler J, Endrizzi M, Qui D, Ianakiev P, Bell-Pedersen D, Nelson MA, Werner-Washburne M, Selitrennikoff CP, Kinsey JA, Braun EL, Zelter A, Schulte U, Kothe GO, Jedd G, Mewes W, Staben C, Marcotte E, Greenberg D, Roy A, Foley K, Naylor J, Stange-Thomann N, Barrett R, Gnerre S, Kamal M, Kamvysselis M, Mauceli E, Bielke C, Rudd S, Frishman D, Krystofova S, Rasmussen C, Metzenberg RL, Perkins DD, Kroken S, Cogoni C, Macino G, Catcheside D, Li W, Pratt RJ, Osmani SA, DeSouza CP, Glass L, Orbach MJ, Berglund JA, Voelker R, Yarden O, Plamann M, Seiler S, Dunlap JC, Radford A, Aramayo R, Natvig DO, Alex LA, Mannhaupt G, Ebbole DJ, Freitag M, Paulsen I, Sachs MS, Lander ES, Nusbaum C, Birren B (2003) The genome sequence of the filamentous fungus Neurospora crassa. Nature 422:859–868

    Article  PubMed  CAS  Google Scholar 

  • Graziani S, Vasnier C, Daboussi MJ (2004) Novel polyketide synthase from Nectria haematococca. Appl Environ Microbiol 70:2984–2988

    Article  PubMed  CAS  Google Scholar 

  • Hock B, Bahn M, Walk RA, Nitschke U (1978) The control of fruiting body formation in the ascomycete Sordaria macrospora Auersw. by regulation of hyphal development. Planta 141:93–103

    Article  Google Scholar 

  • Hoffmeister D, Keller NP (2007) Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep 24:393–416

    Article  PubMed  CAS  Google Scholar 

  • Hofmann K, Stoffel W (1993) TMbase: a database of membrane spanning proteins segments. Biol Chem Hoppe-Seyler 374:166

    Google Scholar 

  • Hood HM, Radford A, Sachs MS (2008) Recommendations for assigning symbols and names to Neurospora crassa genes now that its genome has been sequenced. Fungal Genet Rep 55:29–31

    Google Scholar 

  • Jones MG (2007) The first filamentous fungal genome sequences: Aspergillus leads the way for essential everyday resources or dusty museum specimens? Microbiology 153:1–6

    Article  PubMed  CAS  Google Scholar 

  • Kämper J, Kahmann R, Bölker M, Ma LJ, Brefort T, Saville BJ, Banuett F, Kronstad JW, Gold SE, Müller O, Perlin MH, Wösten HA, de VR, Ruiz-Herrera J, Reynaga-Pena CG, Snetselaar K, McCann M, Pérez-Martin J, Feldbrügge M, Basse CW, Steinberg G, Ibeas JI, Holloman W, Guzman P, Farman M, Stajich JE, Sentandreu R, González-Prieto JM, Kennell JC, Molina L, Schirawski J, Mendoza-Mendoza A, Greilinger D, Münch K, Rössel N, Scherer M, Vranes M, Ladendorf O, Vincon V, Fuchs U, Sandrock B, Meng S, Ho EC, Cahill MJ, Boyce K, Klose J, Klosterman SJ, Deelstra HJ, Ortiz-Castellanos L, Li W, Sanchez-Alonso P, Schreier PH, Häuser-Hahn I, Vaupel M, Koopmann E, Friedrich G, Voss H, Schlüter T, Margolis J, Platt D, Swimmer C, Gnirke A, Chen F, Vysotskaia V, Mannhaupt G, Güldener U, Münsterkötter M, Haase D, Oesterheld M, Mewes HW, Mauceli EW, DeCaprio D, Wade CM, Butler J, Young S, Jaffe DB, Calvo S, Nusbaum C, Galagan J, Birren BW (2006) Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis. Nature 444:97–101

    Article  PubMed  CAS  Google Scholar 

  • Keller NP, Hohn TM (1997) Metabolic pathway gene clusters in filamentous fungi. Fungal Genet Biol 21:17–29

    Article  PubMed  CAS  Google Scholar 

  • Kroken S, Glass NL, Taylor JW, Yoder OC, Turgeon BG (2003) Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proc Nat Acad Sci USA 100:15670–15675

    Article  PubMed  CAS  Google Scholar 

  • Li D, Bobrowicz P, Wilkinson HH, Ebbole DJ (2005) A mitogen-activated protein kinase pathway essential for mating and contributing to vegetative growth in Neurospora crassa. Genetics 170:1091–1104

    Article  PubMed  CAS  Google Scholar 

  • Maniatis T, Fritsch EF, Sambrooke J (1982) Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor

    Google Scholar 

  • Marchler-Bauer A, Bryant SH (2004) CD-Search: protein domain annotations on the fly. Nucleic Acids Res 32:W327–W331

    Article  PubMed  CAS  Google Scholar 

  • Masloff S, Pöggeler S, Kück U (1999) The pro1 + gene from Sordaria macrospora encodes a C6 zinc finger transcription factor required for fruiting body development. Genetics 152:191–199

    PubMed  CAS  Google Scholar 

  • Moore D (1998) Fungal morphogenesis. Cambridge University Press, Cambridge

    Google Scholar 

  • Nakai K, Horton P (1999) PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization. Trends Biochem Sci 24:24–26

    Article  Google Scholar 

  • Nowrousian M (2007) Of patterns and pathways: microarray technologies for the analysis of filamentous fungi. Fungal Biol Rev 21:171–178

    Article  Google Scholar 

  • Nowrousian M, Cebula P (2005) The gene for a lectin-like protein is transcriptionally activated during sexual development, but is not essential for fruiting body formation in the filamentous fungus Sordaria macrospora. BMC Microbiol 5:64

    Article  PubMed  CAS  Google Scholar 

  • Nowrousian M, Masloff S, Pöggeler S, Kück U (1999) Cell differentiation during sexual development of the fungus Sordaria macrospora requires ATP citrate lyase activity. Mol Cell Biol 19:450–460

    PubMed  CAS  Google Scholar 

  • Nowrousian M, Würtz C, Pöggeler S, Kück U (2004) Comparative sequence analysis of Sordaria macrospora and Neurospora crassa as a means to improve genome annotation. Fungal Genet Biol 41:285–292

    Article  PubMed  CAS  Google Scholar 

  • Nowrousian M, Ringelberg C, Dunlap JC, Loros JJ, Kück U (2005) Cross-species microarray hybridization to identify developmentally regulated genes in the filamentous fungus Sordaria macrospora. Mol Genet Genomics 273:137–149

    Article  PubMed  CAS  Google Scholar 

  • Nowrousian M, Frank S, Koers S, Strauch P, Weitner T, Ringelberg C, Dunlap JC, Loros JJ, Kück U (2007) The novel ER membrane protein PRO41 is essential for sexual development in the filamentous fungus Sordaria macrospora. Mol Microbiol 64:923–937

    Article  PubMed  CAS  Google Scholar 

  • Perkins DD, Radford A, Sachs MS (2001) The Neurospora compendium: chromosomal loci. Academic Press, San Diego

    Google Scholar 

  • Perrin RM, Fedorova ND, Bok JW, Cramer RA, Wortman JR, Kim HS, Nierman WC, Keller NP (2007) Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA. PLoS Pathog 3:e50

    Article  PubMed  CAS  Google Scholar 

  • Pöggeler S, Kück U (2006) Highly efficient generation of signal transduction knockout mutants using a fungal strain deficient in the mammalian ku70 ortholog. Gene 378:1–10

    Article  PubMed  CAS  Google Scholar 

  • Pöggeler S, Nowrousian M, Jacobsen S, Kück U (1997) An efficient procedure to isolate fungal genes from an indexed cosmid library. J Microbiol Meth 29:49–61

    Article  Google Scholar 

  • Pöggeler S, Nowrousian M, Kück U (2006a) Fruiting-body development in ascomycetes. In: Kües U, Fischer R (eds) The mycota I. Springer, Berlin, pp 325–355

    Google Scholar 

  • Pöggeler S, Nowrousian M, Ringelberg C, Loros JJ, Dunlap JC, Kück U (2006b) Microarray and real time PCR analyses reveal mating type-dependent gene expression in a homothallic fungus. Mol Genet Genomics 275:492–503

    Article  PubMed  CAS  Google Scholar 

  • Sambrook J, Russell DW (2001) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  • Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416

    Article  PubMed  CAS  Google Scholar 

  • Stuart JM, Segal E, Koller D, Kim SK (2003) A gene-coexpression network for global discovery of conserved genetic modules. Science 302:249–255

    Article  PubMed  CAS  Google Scholar 

  • Tusnady GE, Simon I (2001) The HMMTOP transmembrane topology prediction server. Bioinformatics 17:849–850

    Article  PubMed  CAS  Google Scholar 

  • Walsh CT (2004) Polyketide and nonribosomal peptide antibiotics: modularity and versatility. Science 303:1805–1810

    Article  PubMed  CAS  Google Scholar 

  • Wessels JGH (1993) Fruiting in the higher fungi. Adv Microb Physiol 34:147–202

    Article  PubMed  CAS  Google Scholar 

  • Wolf JC, Mirocha CJ (1973) Regulation of sexual reproduction in Gibberella zeae (Fusarium roseum ‘Graminearum’) by F-2 (Zearalenone). Can J Microbiol 19:725–734

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman WC, Blanchette RA, Burnes TA, Farrell RL (1995) Melanin and perithecial development in Ophiostoma piliferum. Mycologia 87:857–863

    Article  CAS  Google Scholar 

Download references

Acknowledgments

I would like to thank Prof. Dr. Ulrich Kück for his generous support, Swenja Ellßel, Gisela Isowitz, Silke Nimtz, and Susanne Schlewinski for excellent technical assistance, and Sandra Frank for help with some of the experiments. This study was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 480 project A1 and grant NO 407/2-1).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Minou Nowrousian.

Additional information

Communicated by G. Braus.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 104 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nowrousian, M. A novel polyketide biosynthesis gene cluster is involved in fruiting body morphogenesis in the filamentous fungi Sordaria macrospora and Neurospora crassa . Curr Genet 55, 185–198 (2009). https://doi.org/10.1007/s00294-009-0236-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00294-009-0236-z

Keywords

Navigation