All Title Author
Keywords Abstract

PLOS ONE  2013 

Aspergillus nidulans Synthesize Insect Juvenile Hormones upon Expression of a Heterologous Regulatory Protein and in Response to Grazing by Drosophila melanogaster Larvae

DOI: 10.1371/journal.pone.0073369

Full-Text   Cite this paper   Add to My Lib


Secondary metabolites are known to serve a wide range of specialized functions including communication, developmental control and defense. Genome sequencing of several fungal model species revealed that the majority of predicted secondary metabolite related genes are silent in laboratory strains, indicating that fungal secondary metabolites remain an underexplored resource of bioactive molecules. In this study, we combine heterologous expression of regulatory proteins in Aspergillus nidulans with systematic variation of growth conditions and observe induced synthesis of insect juvenile hormone-III and methyl farnesoate. Both compounds are sesquiterpenes belonging to the juvenile hormone class. Juvenile hormones regulate developmental and metabolic processes in insects and crustaceans, but have not previously been reported as fungal metabolites. We found that feeding by Drosophila melanogaster larvae induced synthesis of juvenile hormone in A. nidulans indicating a possible role of juvenile hormone biosynthesis in affecting fungal-insect antagonisms.


[1]  Aminov RI (2009) The role of antibiotics and antibiotic resistance in nature. Environmental Microbiology 11: 2970–2988.
[2]  Kempken F, Rohlfs M (2010) Fungal secondary metabolite biosynthesis - a chemical defence strategy against antagonistic animals? Fungal Ecology 3: 107–114.
[3]  Rohlfs M, Churchill ACL (2011) Fungal secondary metabolites as modulators of interactions with insects and other arthropods. Fungal Genetics and Biology 48: 23–34.
[4]  Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. Journal of Natural Products 70: 461–477.
[5]  Reddy K, Salleh B, Saad B, Abbas H, Abel C, et al. (2010) An overview of mycotoxin contamination in foods and its implications for human health. Toxin Reviews 29: 3–26.
[6]  Galagan JE, Calvo SE, Cuomo C, Ma LJ, Wortman JR, et al. (2005) Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438: 1105–1115.
[7]  Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, et al. (2007) Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nat Biotech 25: 221–231 10.1038/nbt1282.
[8]  Gross H (2007) Strategies to unravel the function of orphan biosynthesis pathways: recent examples and future prospects. Applied Microbiology and Biotechnology 75: 267–277.
[9]  Brakhage AA, Schroeckh V (2011) Fungal secondary metabolites - Strategies to activate silent gene clusters. Fungal Genetics and Biology 48: 15–22.
[10]  Chiang YM, Chang SL, Oakley BR, Wang CCC (2011) Recent advances in awakening silent biosynthetic gene clusters and linking orphan clusters to natural products in microorganisms. Current Opinion in Chemical Biology 15: 137–143.
[11]  Bok JW, Chiang YM, Szewczyk E, Reyes-Domingez Y, Davidson AD, et al. (2009) Chromatin-level regulation of biosynthetic gene clusters. Nature Chemical Biology 5: 462–464.
[12]  Bergmann S, Funk AN, Scherlach K, Schroeckh V, Shelest E, et al. (2010) Activation of a silent fungal polyketide biosynthesis pathway through regulatory cross talk with a cryptic non-ribosomal peptide synthetase gene cluster. Applied and Environmental Microbiology 76: 8143–8149.
[13]  Hansen BG, Salomonsen B, Nielsen MT, Nielsen JB, Hansen NB, et al. (2011) Versatile enzyme expression and characterization system for Aspergillus nidulans, with the Penicillium brevicompactum polyketide synthase gene from the mycophenolic acid gene cluster as a test case. Applied and Environmental Microbiology 77: 3044–3051.
[14]  Nielsen ML, Nielsen JB, Rank C, Klejnstrup ML, Holm DK, et al. (2011) A genome-wide polyketide synthase deletion library uncovers novel genetic links to polyketides and meroterpenoids in Aspergillus nidulans. Fems Microbiology Letters 321: 157–166.
[15]  Nagaraju GPC (2007) Is methyl farnesoate a crustacean hormone? Aquaculture 272: 39–54.
[16]  Wilson TG (2004) The molecular site of action of juvenile hormone and juvenile hormone insecticides during metamorphosis: how these compounds kill insects. Journal of Insect Physiology 50: 111–121.
[17]  Gilbert LI, Granger NA, Roe RM (2000) The juvenile hormones: historical facts and speculations on future research directions. Insect Biochemistry and Molecular Biology 30: 617–644.
[18]  Marrs TC (2012) Toxicology of insecticides to mammals. Pest Management Science 68: 1332–1336.
[19]  Minakuchi C, Riddiford LM (2006) Insect juvenile hormone action as a potential target of pest management. Journal of Pesticide Science 31: 77–84.
[20]  Andersen MR, Vongsangnak W, Panagiotou G, Salazar MP, Lehmann L, et al. (2008) A trispecies Aspergillus microarray: Comparative transcriptomics of three Aspergillus species. Proceedings of the National Academy of Sciences of the United States of America 105: 4387–4392.
[21]  Panagiotou G, Andersen MR, Grotkjaer T, Regueira TB, Hofmann G, et al.. (2008) Systems analysis unfolds the relationship between the phosphoketolase pathway and growth in Aspergillus nidulans. Plos One 3..
[22]  Panagiotou G, Andersen MR, Grotkjaer T, Regueira TB, et al. (2009) Studies of the production of fungal polyketides in Aspergillus nidulans by using systems biology tools. Applied and Environmental Microbiology 75: 2212–2220.
[23]  Andersen MR, Nielsen JB, Klitgaard A, Petersen LM, Zachariasen M, et al. (2013) Accurate prediction of secondary metabolite gene clusters in filamentous fungi. Proceedings of the National Academy of Sciences of the United States of America 110: E99–E107.
[24]  MacPherson S, Larochelle M, Turcotte B (2006) A fungal family of transcriptional regulators: The zinc cluster proteins. Microbiology and Molecular Biology Reviews 70: 583–604.
[25]  Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic Local Alignment Search Tool. Journal of Molecular Biology 215: 403–410.
[26]  Kuhnz W, Rembold H (1981) C-13 nuclear magnetic-resonance spectra of juvenile hormone-III, some of Its derivatives, and of analogous compounds. Organic Magnetic Resonance 16: 138–140.
[27]  Belles X, Martin D, Piulachs MD (2005) The mevalonate pathway and the synthesis of juvenile hormone in insects. PALO ALTO: ANNUAL REVIEWS. 199.
[28]  Toong YC (1988) Schooley DA, Baker FC (1988) Isolation of insect juvenile Hormone-III from a plant. Nature 333: 170–171.
[29]  Flatt T, Tu MP, Tatar M (2005) Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. Bioessays 27: 999–1010.
[30]  Trienens M, Keller NP, Rohlfs M (2010) Fruit, flies and filamentous fungi - experimental analysis of animal-microbe competition using Drosophila melanogaster and Aspergillus mould as a model system. Oikos 119: 1765–1775.
[31]  Asadollahi MA, Maury J, Patil KR, Schalk M, Clark A, et al. (2009) Enhancing sesquiterpene production in Saccharomyces cerevisiae through in silico driven metabolic engineering. Metabolic Engineering 11: 328–334.
[32]  Schroeckh V, Scherlach K, Nutzmann HW, Shelest E, Schmidt-Heck W, et al. (2009) Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proceedings of the National Academy of Sciences of the United States of America 106: 14558–14563.
[33]  Nielsen ML, Albertsen L, Lettier G, Nielsen JB, Mortensen UH (2006) Efficient PCR-based gene targeting with a recyclable marker for Aspergillus nidulans. Fungal Genetics and Biology 43: 54–64.
[34]  Cove DJ (1966) Induction and Repression of Nitrate Reductase in Fungus Aspergillus Nidulans. Biochimica et Biophysica Acta 113: : 51–&.
[35]  Frisvad JC, Samson RA (2004) Polyphasic taxonomy of Penicillium subgenus Penicillium. A guide to identification of food and air-borne terverticillate Penicilia and their mycotoxons. Studies in Mycology 49: 1–173.
[36]  Norholm MHH (2010) A mutant Pfu DNA polymerase designed for advanced uracil-excision DNA engineering. Bmc Biotechnology 10 10.1186/1472-6750-10-21..
[37]  Southern E (2006) Southern blotting. Nature Protocols 1: 518–525.
[38]  Smedsgaard J (1997) Micro-scale extraction procedure for standardized screening of fungal metabolite production in cultures. Journal of Chromatography A 760: 264–270.
[39]  Laatsch H (2009) AntiBase 2009. The natural compound identifier. Wiley-VCH GmpH & Co, Weinheim, Germany.
[40]  Larsen TO, Frisvad JC (1994) A simple method for collection of volatile metabolites from fungi based on diffusive sampling from petri dishes. Journal of Microbiological Methods 19: 297–305.
[41]  Rohlfs M (2006) Genetic variation and the role of insect life history traits in the ability of Drosophila larvae to develop in the presence of a competing filamentous fungus. Evolutionary Ecology 20: 271–289.


comments powered by Disqus

Contact Us


微信:OALib Journal