Pérez-Contreras et al. 2025

Neurospora: A casi 200 años de su primer reporte, un hongo con historia y ciencia

Neurospora: Nearly 200 years after its discovery, a fungus with history and science

Autor(es): Serafín Pérez-Contreras, Dora Angélica Ávalos de la Cruz, Manuel Alejandro Lizardi Jiménez, José Andrés Herrera Corredor, Obdulia Baltazar Bernal y Ricardo Hernández Martínez

Fuente: Mexican Journal of Technology and Engineering, Vol. 4, No. 1, pp. 4-16

DOI: https://doi.org/10.61767/mjte.004.1.0416

Resumen

El género de hongos filamentosos Neurospora tuvo su primer reporte en el año 1843 como un contaminante persistente en panaderías francesas, desde entonces, ha evolucionado de ser una plaga para convertirse en un organismo modelo fundamental para la ciencia. Su relevancia inició en los años 40 con los trabajos de Beadle y Tatum, quienes realizaron estudios con Neurospora crassa para establecer la relación resumida en “un gen, una proteína”, revolucionando la genética y la bioquímica, al punto de ser acreedores al premio nobel de Fisiología o Medicina en 1958. Además, estudios posteriores revelaron su papel en la comprensión de los ritmos circadianos, identificando mecanismos moleculares conservados en eucariotas, como los bucles de retroalimentación entre proteínas reguladoras. En biotecnología, la investigación con Neurospora ha tenido aportaciones por su capacidad para producir enzimas hidrolíticas (celulasas, xilanasas, amilasas) con capacidad para degradar la biomasa vegetal, ofreciendo alternativas para la producción de biocombustibles y compuestos industriales. Así mismo, han existido estudios enfocados en la fermentación de residuos agrícolas para mejorar su valor nutricional, destacando aplicaciones en alimentación sostenible. Con un ciclo de vida corto, una mayor complejidad en comparación a las levaduras y facilidad en su manejo, Neurospora sigue siendo una herramienta versátil en investigación. Su historia ejemplifica cómo un organismo que fue considerado un problema se convirtió en un aliado científico multidisciplinario, con potencial continuo para la innovación en sostenibilidad y biotecnología.

Palabras clave: Organismo modelo, Neurospora crassa, hongos filamentosos.

Abstract

The filamentous fungus genus Neurospora was first reported in 1843 as a persistent contaminant in French bakeries. Since then, it has evolved from a pest into a key model organism in scientific research. Its significance emerged in the 1940s with the notable work of Beadle and Tatum, who used Neurospora crassa to establish the “one gene, one enzyme” hypothesis, revolutionizing genetics and biochemistry—an achievement that earned them the 1958 Nobel Prize in Physiology or Medicine. Further studies revealed Neurospora‘s role in understanding circadian rhythms, uncovering conserved molecular mechanisms in eukaryotes, such as feedback loops between regulatory proteins. In biotechnology, Neurospora research has contributed to the production of hydrolytic enzymes (cellulases, xylanases, amylases) capable of breaking down plant biomass, offering promising alternatives for biofuel and industrial compound production. Additionally, studies have explored its use in fermentation of agricultural residues to enhance their nutritional value, highlighting applications in sustainable food production. With a short life cycle, greater complexity than yeasts, and ease of handling, Neurospora remains a versatile research tool. Its history exemplifies how an organism once considered as a problem became a multidisciplinary scientific ally with continuous potential for innovation in sustainability and biotechnology.

Keywords: model organism, Neurospora crassa, filamentous fungi.

References

Alhomodi, A. F., Gibbons, W. R., & Karki, B. (2022). Estimation of cellulase production by Aureobasidium pullulans, Neurospora crassa, and Trichoderma reesei during solid and submerged state fermentation of raw and processed canola meal. Bioresource Technology Reports, 18, 101063. https://doi.org/10.1016/j.biteb.2022.101063

Barratt, R. W., & Garnjobst, L. (1949). Genetics of a colonial microconidiating mutant strain of Neurospora crassa. Genetics, 34(4), 351–369. https://doi.org/10.1093/genetics/34.4.351

Bartholomai, B. M., Ruwe, K. M., Thurston, J., Jha, P., Scaife, K., Simon, R., Abdelmoteleb, M., Goodman, R. E., & Farhi, M. (2022). Safety evaluation of Neurospora crassa mycoprotein for use as a novel meat alternative and enhancer. Food and Chemical Toxicology, 168, 113342. https://doi.org/10.1016/j.fct.2022.113342

Beadle, G. W. (1945). Genetics and metabolism in Neurospora. Physiological Reviews, 25(4), 643–663. https://doi.org/10.1152/physrev.1945.25.4.643

Beadle, G. W., Mitchell, H. K., & Nyc, J. F. (1947). Kynurenine as an Intermediate in the Formation of Nicotinic Acid from Tryptophane by Neurospora. Proceedings of the National Academy of Sciences, 33(6), 155–158. https://doi.org/10.1073/pnas.33.6.155

Bell-Pedersen, D., Dunlap, J. C., & Loros, J. J. (1992). The Neurospora circadian clock-controlled gene, ccg-2, is allelic to eas and encodes a fungal hydrophobin required for formation of the conidial rodlet layer. Genes & Development, 6(12a), 2382–2394. https://doi.org/10.1101/gad.6.12a.2382

Bonner, D. (1946). Further studies of mutant strains of Neurospora requiring isoleucine and valine. Journal of Biological Chemistry, 166(2), 545–554. https://doi.org/10.1016/s0021-9258(17)35192-x

Chávez-Escalante, G., Méndez-González, F., Espinosa-Ramírez, B., & Estrada-Martínez, R. (2022). Biotransformation of the organic fraction of municipal solid wastes to bioethanol. Mexican Journal of Technology and Engineering, 1(1), 9–14. https://doi.org/10.61767/mjte.001.1.0914

Cheng, P., Yang, Y., & Liu, Y. (2001). Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock. Proceedings of the National Academy of Sciences, 98(13), 7408–7413. https://doi.org/10.1073/pnas.121170298

Colson, B. (1934). The Cytology and Morphology of Neurospora tetrasperma Dodge. Annals of Botany, os-48(1), 211–224. https://doi.org/10.1093/oxfordjournals.aob.a090436

Coradetti, S. T., Xiong, Y., & Glass, N. L. (2013). Analysis of a conserved cellulase transcriptional regulator reveals inducer‐independent production of cellulolytic enzymes in Neurospora crassa. MicrobiologyOpen, 2(4), 595–609. https://doi.org/10.1002/mbo3.94

Davis, R. H., & De Serres, F. J. (1970). [4] Genetic and microbiological research techniques for Neurospora crassa. In Methods in enzymology on CD-ROM/Methods in enzymology (pp. 79–143). https://doi.org/10.1016/0076-6879(71)17168-6

Dettman, J. R., & Taylor, J. W. (2004). Mutation and evolution of microsatellite Loci in Neurospora. Genetics, 168(3), 1231–1248. https://doi.org/10.1534/genetics.104.029322

Dodge, B. O. (1939). A new dominant lethal in Neurospora*. Journal of Heredity, 30(11), 466–474. https://doi.org/10.1093/oxfordjournals.jhered.a104632

Dogaris, I., Vakontios, G., Kalogeris, E., Mamma, D., & Kekos, D. (2008). Induction of cellulases and hemicellulases from Neurospora crassa under solid-state cultivation for bioconversion of sorghum bagasse into ethanol. Industrial Crops and Products, 29(2–3), 404–411. https://doi.org/10.1016/j.indcrop.2008.07.008

Emerson, S. (1950). The growth phase in Neurospora corresponding to the logarithmic phase in unicellular organisms. Journal of Bacteriology, 60(3), 221–223. https://doi.org/10.1128/jb.60.3.221-223.1950

Feldman, J. F., & Hoyle, M. N. (1973). Isolation of circadian clock mutants of Neurospora crassa. Genetics, 75(4), 605–613. https://doi.org/10.1093/genetics/75.4.605

Galagan, J. E., Calvo, S. E., Borkovich, K. A., Selker, E. U., Read, N. D., Jaffe, D., FitzHugh, W., Ma, L., Smirnov, S., Purcell, S., Rehman, B., Elkins, T., Engels, R., Wang, S., Nielsen, C. B., Butler, J., Endrizzi, M., Qui, D., Ianakiev, P., . . . Birren, B. (2003). The genome sequence of the filamentous fungus Neurospora crassa. Nature, 422(6934), 859–868. https://doi.org/10.1038/nature01554

Goddard, D. R. (1935). The reversible heat activation inducing germination and increased respiration in the ascospores of Neurospora tetrasperma. The Journal of General Physiology, 19(1), 45–60. https://doi.org/10.1085/jgp.19.1.45

Honda, S., Eusebio-Cope, A., Miyashita, S., Yokoyama, A., Aulia, A., Shahi, S., Kondo, H., & Suzuki, N. (2020). Establishment of Neurospora crassa as a model organism for fungal virology. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-19355-y

Horowitz, N. (1950). Biochemical genetics of Neurospora. Advances in Genetics, 33–71. https://doi.org/10.1016/s0065-2660(08)60082-6

Hotta, C. T. (2021). From crops to shops: how agriculture can use circadian clocks. Journal of Experimental Botany, 72(22), 7668–7679. https://doi.org/10.1093/jxb/erab371

Houlahan, M. B., Beadle, G. W., & Calhoun, H. G. (1949). Linkage studies with biochemical mutants of Neurospora crassa. Genetics, 34(5), 493–507. https://doi.org/10.1093/genetics/34.5.493

Kollath-Leiß, K., Repnik, U., Winter, H., Winkelmann, H., Freund, A. S., & Kempken, F. (2024). The First Observation of the Filamentous Fungus Neurospora crassa Growing in the Roots of the Grass Brachypodium distachyon. Journal of Fungi, 10(7), 487. https://doi.org/10.3390/jof10070487

Lee, K., Loros, J. J., & Dunlap, J. C. (2000). Interconnected feedback loops in the Neurospora circadian system. Science, 289(5476), 107–110. https://doi.org/10.1126/science.289.5476.107

Lindegren, C. C. (1936). A six-point map of the sex-chromosome of Neurospora crassa. Journal of Genetics, 32(2), 243–256. https://doi.org/10.1007/bf02982680

Liu, Y., Garceau, N. Y., Loros, J. J., & Dunlap, J. C. (1997). Thermally regulated translational control of FRQ mediates aspects of temperature responses in the Neurospora circadian clock. Cell, 89(3), 477–486. https://doi.org/10.1016/s0092-8674(00)80228-7

Loros, J. J., Denome, S. A., & Dunlap, J. C. (1989). Molecular cloning of genes under control of the circadian clock in Neurospora. Science, 243(4889), 385–388. https://doi.org/10.1126/science.2563175

Menkis, A., Jacobson, D. J., Gustafsson, T., & Johannesson, H. (2008). The Mating-Type Chromosome in the Filamentous Ascomycete Neurospora tetrasperma Represents a Model for Early Evolution of Sex Chromosomes. PLoS Genetics, 4(3), e1000030. https://doi.org/10.1371/journal.pgen.1000030

Merrow, M., Brunner, M., & Roenneberg, T. (1999). Assignment of circadian function for the Neurospora clock gene frequency. Nature, 399(6736), 584–586. https://doi.org/10.1038/21190

Mishra, C., Keskar, S., & Rao, M. (1984). Production and Properties of Extracellular Endoxylanase from Neurospora crassa. Applied and Environmental Microbiology, 48(1), 224–228. https://doi.org/10.1128/aem.48.1.224-228.1984

Perkins, D. D., Radford, A., & Sachs, M. S. (2000). The Neurospora Compendium: Chromosomal loci. https://ci.nii.ac.jp/ncid/BA84287773

Romero, M., Aguado, J., González, L., & Ladero, M. (1999). Cellulase production by Neurospora crassa on wheat straw. Enzyme and Microbial Technology, 25(3–5), 244–250. https://doi.org/10.1016/s0141-0229(99)00035-6

Schafmeier, T., Haase, A., Káldi, K., Scholz, J., Fuchs, M., & Brunner, M. (2005). Transcriptional feedback of Neurospora circadian clock gene by Phosphorylation-Dependent inactivation of its transcription factor. Cell, 122(2), 235–246. https://doi.org/10.1016/j.cell.2005.05.032

Schmoll, M., Tian, C., Sun, J., Tisch, D., & Glass, N. L. (2012). Unravelling the molecular basis for light modulated cellulase gene expression – the role of photoreceptors in Neurospora crassa. BMC Genomics, 13(1), 127. https://doi.org/10.1186/1471-2164-13-127

Shahryari, Z., Fazaelipoor, M. H., Ghasemi, Y., Lennartsson, P. R., & Taherzadeh, M. J. (2019). Amylase and Xylanase from Edible Fungus Neurospora intermedia: Production and Characterization. Molecules, 24(4), 721. https://doi.org/10.3390/molecules24040721

Shear, C. L., y Dodge, B. O. (1927). Life histories and heterothallism of the red bread-mold fungi of the Monilia sitophila group (pp. 1019-1042). Washington, DC: US Government Printing Office. https://eurekamag.com/research/024/949/024949842.php?srsltid=AfmBOop43BLfWARb7eyKLBqAEShaPYPx9GqHTmdF9oURQdDHT–Javfh

Soccol, C. R., Da Costa, E. S. F., Letti, L. a. J., Karp, S. G., Woiciechowski, A. L., & De Souza Vandenberghe, L. P. (2017). Recent developments and innovations in solid state fermentation. Biotechnology Research and Innovation, 1(1), 52–71. https://doi.org/10.1016/j.biori.2017.01.002

Strauss, B. S. (2016). Biochemical Genetics and Molecular Biology: the contributions of George Beadle and Edward Tatum. Genetics, 203(1), 13–20. https://doi.org/10.1534/genetics.116.188995

Svedberg, J., Vogan, A. A., Rhoades, N. A., Sarmarajeewa, D., Jacobson, D. J., Lascoux, M., Hammond, T. M., & Johannesson, H. (2021). An introgressed gene causes meiotic drive in Neurospora sitophila. Proceedings of the National Academy of Sciences, 118(17). https://doi.org/10.1073/pnas.2026605118

Tatum, E. L., & Bell, T. T. (1946). Neurospora. III. Biosynthesis of thiamin. American Journal of Botany, 33(1), 15. https://doi.org/10.2307/2437486

Verma, N., & Kumar, V. (2020). Impact of process parameters and plant polysaccharide hydrolysates in cellulase production by Trichoderma reesei and Neurospora crassa under wheat bran based solid state fermentation. Biotechnology Reports, 25, e00416. https://doi.org/10.1016/j.btre.2019.e00416

Yazdi, M. T., Woodward, J. R., & Radford, A. (1990). The cellulase complex of Neurospora crassa: activity, stability and release. Journal of General Microbiology, 136(7), 1313–1319. https://doi.org/10.1099/00221287-136-7-1313

Yu, J., Fu, Y., Deng, Z., Fan, Y., & Li, H. (2020). Effects of soluble dietary fiber from soybean residue fermented by Neurospora crassa on the intestinal flora in rats. Food & Function, 11(9), 7433–7445. https://doi.org/10.1039/d0fo01093f

Zhao, C., Zhao, J., Han, J., Mei, Y., & Fang, H. (2024). Improved consolidated bioprocessing for itaconic acid production by simultaneous optimization of cellulase and metabolic pathway of Neurospora crassa. Biotechnology for Biofuels and Bioproducts, 17(1). https://doi.org/10.1186/s13068-024-02505-5

Zheng, L., Yu, X., Wei, C., Qiu, L., Yu, C., Xing, Q., Fan, Y., & Deng, Z. (2019). Production and characterization of a novel alkaline protease from a newly isolated Neurosporacrassa through solid-state fermentation. LWT, 122, 108990. https://doi.org/10.1016/j.lwt.2019.108990