Jae-hyuk Yu

Position title: Professor

Email: jyu1@wisc.edu

Phone: 608-262-4696

Molecular genetics and genomics of spore formation and mycotoxin biosynthesis in filamentous fungi

3155 Microbial Sciences Building, 1550 Linden Dr.
Ph.D., The University of Wisconsin-Madison (1995), Postdoctoral Research: Texas A&M University, 1995-1998; Investigator (Scientist): Cereon Genomics, LLC. 1998-2000
Research Interests
Molecular genetics and genomics of spore formation and mycotoxin biosynthesis in filamentous fungi
Research Fields
Development, Gene Expression, Genomics & Proteomics, Fungi

Research Description:
Aflatoxins (AFs) are a serious and present problem. Over half of the world’s population is exposed to unmonitored levels of potent, carcinogenic AFs through their daily diet. AFs are a group of mycotoxins produced mainly by the ubiquitous soil fungus Aspergillus flavus. The main means of dissemination of this fungus is by the production of a massive number of asexual spores (conidia) which can be dispersed in the soil and air. These spores are carried to corn ears by insects or wind where they grow in maize kernels and produce aflatoxin B1 (AFB1). When feed contaminated with AFB1 is consumed by a cow, it is metabolized to AFM1 (M for milk), which is also highly toxic and carcinogenic. AFs threaten global food safety by contaminating ~25% of the world food supply. Among AFs, AFB1 is the most potent naturally occurring carcinogen; it is 200 times more potent than the major carcinogen benzo-a-pyrene. AFs are projected to cause up to 28% of the 550,000–600,000 new liver cancer cases diagnosed each year globally. Furthermore, consumption of AF-contaminated food is associated with stunted growth in children, damage to the immune system, and high mortality rates, especially in developing countries. Even at trace levels, e.g., 20 ppb (U.S. FDA action level), AFs can be dangerous, and foods contaminated with higher amounts of total AFs are not fit for human consumption.

Methods to control AF contamination both pre- and post-harvest have shown only marginal success. No currently used AF control methods are suitable for effective and practical elimination of AFs in food products. Consequently, the AF problem will grow further, threatening global food safety, food security, and public health. AFs also pose a significant economic burden, causing an estimated 25% or more of the world’s food crops to be destroyed annually (WHO).

We have developed a proprietary AF-degrading product called D-Tox by growing food-grade Aspergillus oryzae strains in a novel medium under specific culture conditions. A. oryzae strains have been used to produce soy sauce, miso, sake, and many other food and drinks and are classified as GRAS (Generally Recognized as Safe) organisms for use in food products. D-Tox can degrade and detoxify a lethal level of AFB1 (100 ppm) to non-toxic aflatoxin D1 (AFD1), which is further degraded into unknown product(s). To validate the safety of the D-Tox producing strains, we carried out whole genome analyses of several strains of A. oryzae and found that they are unable to produce AFs or other mycotoxins. Unlike other methods used for AF detoxification, e.g., nixtamalization of corn, D-Tox is stable and even effective at high temperatures (95~100ºC), and the degradation process is irreversible. We anticipate that D-Tox can be used to eliminate AFs in maize, rice, wheat, barley, oats, sorghum, and milk containing aflatoxin M1 (AFM1).

We are currently investigating the chemistry, toxicology, and practical applications of D-Tox and determine the mechanisms by which it degrades AFs with: Aim 1) Identify D-Tox compound(s) and understand the fate of AFB1 degradation. Aim 2) Examine in vitro toxicity of D-Tox and its effectiveness in detoxifying AFB1. Aim 3) Examine the activity spectrum and practical applications of D-Tox on AFs in various foods and feeds, including milk (AFM1). In addition, we envision several D-Tox application methods, including soaking/misting crops with D-Tox, cooking plant-based foods with D-Tox (cooking process), or adding a lyophilized D-Tox tablet to milk.

Representative Publications:
Search PubMed for more publications by Jae-hyuk Yu

Park, H-S., Yu, Y.M., Lee, M-K., Maeng, P.J. Kim, S.C., and Yu, J.-H. 2015. Velvet-mediated repression of β-glucan synthesis in Aspergillus nidulans spores. Scientific Rep. 5:10199 | DOI: 10.1038/srep10199

Alkhayyat, F., Kim, S.C., and Yu, J.-H. 2015. Genetic control of asexual development in Aspergillus fumigatus, Advances in Applied Microbiology, 90: 93-107

Chen, W, Lee, M.-K., Jefcoate, C., Kim, S.C., Chen, F., and Yu, J.-H. 2014. Fungal cytochrome P450 monooxygenases: Their distribution, structure, functions, family expansion, and evolutionary origin. Genome Biology and Evolution. 6: 1620-1634.

Lee, M.-K., Kwon, N.-J., Choi, J.-M., Lee, I.-S., Jung, S. and Yu, J.-H., 2014. NsdD is a key repressor of asexual development in Aspergillus nidulans. Genetics, 197: 159-173 doi: 10.1534/genetics.114.161430

Park, H.-S., Nam, T.-Y., Han, K.-H., Kim, S.-C., and Yu, J.-H., 2014. VelC positively controls sexual development in Aspergillus nidulans. PLoS ONE, 9(2): e89883. doi:10.1371/journal.pone.0089883

Alkhayyat, F. and Yu, J.-H. 2014. Upstream Regulation of Mycotoxin Biosynthesis, Advances in Applied Microbiology, 86: 251-278 doi: 10.1016/B978-0-12-800262-9.00005-6 (Invited Review)

Ahmed, Y.L.*, Gerke, J.*, Park, H-S.*, Bayram, Ö, Neumann, P., Ni, M., Dickmanns, M., Kim, S.C., Yu, J.-H., Braus, G.H., Ficner, R. 2013. The Velvet family of fungal regulators contains a DNA-binding domain structurally similar to NF-kB. PLoS Biology 11(12): e1001750. doi:10.1371/journal.pbio.1001750 (* Equal contribution, Co-Corresponding Authors underlined) – Weekly Editors’ Pick.

Kong, Q., Long, W., Liu, Z., Kwon, N.-J., Kim, S.-C. and Yu, J.-H. 2013. Gbeta-like CpcB plays a crucial role for growth and development of Aspergillus nidulans and Aspergillus fumigatus. PLoS ONE 8(7): e70355. doi:10.1371/journal.pone.0070355

Shin, K.-S., Park, H.-S., Kim, Y.-H. and Yu, J.-H. 2013. Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus. J Proteomics 87:40-52. doi: 10.1016/j.jprot.2013.05.009.

Jeong, K.-C., and Yu, J.-H. 2012. Investigation of in vivo protein interactions in Aspergillus spores. Methods in Molecular Biology 944: 251-257. doi:10.1007/978-1-62703-122-6_18.

Park, H.-S., and Yu, J.-H. 2012. Multi-Copy Genetic Screen in Aspergillus nidulans. Methods in Molecular Biology 944: 183-190. doi:10.1007/978-1-62703-122-6_13.

Park, H-S., and Yu, J-H. 2012. Genetic control of asexual sporulation in filamentous fungi, Current Opinion in Microbiology, 15: 669-677. doi:10.1016/j.mib.2012.09.006 (Invited Review)

Kwon, N-J., Park, H-S., Jung, S., Kim, S.C., and Yu, J-H. 2012. The putative guanine nucleotide exchange factor RicA mediates upstream signaling for growth and development in Aspergillus. Eukaryotic Cell 11: 1399-1412

Park, H-S., Ni, M., Jeong, K-C., Kim, Y-H., and Yu, J-H. 2012. The role, interaction and regulation of the velvet regulator VelB in Aspergillus nidulans, PLoS ONE 7(9): e45935. doi:10.1371/journal.pone.0045935

Park, H-S., Bayram, Ö, Braus, G.H., Kim, S-C., and Yu, J-H. 2012. Characterization of the velvet regulators in Aspergillus fumigatus. Molecular Microbiology. 86: 937-953 DOI: 10.1111/mmi.12032

Bayram, Ö.S., Bayram, Ö, Valerius, O., Park, H.-S., Irniger S., Gerke, J., Ni, M., Han, K.-H., Yu, J.-H., and Braus, G.H. 2010. LaeA control of velvet family regulatory proteins for light-dependent development and fungal cell-type specificity. PLoS GENETICS, 6(12):e1001226.

Tao, L., and Yu, J.-H. 2011. AbaA and WetA govern distinct stages of Aspergillus fumigatus development. Microbiology-SGM, 157: 313 – 326. doi:10.1099/mic.0.044271-0 Yu, J.-H. 2010. Regulation of Development in Aspergillus nidulans and Aspergillus fumigatus. Mycobiology, 38: 229-237.

Xiao, P., Shin, K.-S., Wang, T., and Yu, J.-H. 2010. Aspergillus fumigatus flbB encodes two basic leucine zipper domain (bZIP) proteins required for proper asexual development and gliotoxin production. Eukaryotic Cell, 9: 1711-1723.

Kwon, N.-J., Shin, K.-S., and Yu, J-H. 2010. Characterization of the developmental regulator FlbE in Aspergillus fumigatus and Aspergillus nidulans. Fungal Genetics and Biology, 47: 981-993.

Kwon, N.-J., Garzia, A., Espeso, E.A., Ugalde, U., and Yu, J-H. 2010. FlbC is a putative nuclear C2H2 transcription factor regulating development in Aspergillus nidulans. Molecular Microbiology 77: 1203-1219.

Shin, K.-S., Kwon, N.-J., Park, H.-S., Kwon, G.-S., and Yu, J.-H. 2009. Differential roles of the ChiB chitinase in autolysis and cell death of Aspergillus nidulans. Eukaryotic Cell, 8:738-746.

Bayram, Ö, Krappmann, S., Ni, M., Bok, J.-W., Helmstaedt, K., Valerius, O., Braus-Stromeyer, S., Kwon, N-J., Keller, N.P., Yu, J.-H., and Braus, G.H. 2008. The velvet complex coordinates light, fungal development and secondary metabolism. Science, 320: 1504-1506.

Ni, M. and Yu, J.-H. 2007. A novel regulator couples sporogenesis and trehalose biogenesis in Aspergillus nidulans. PLoS ONE 2(10):e970 doi:10.1371/journal.pone.0000970.

Mah, J.-H., and Yu, J.-H. 2006. Upstream and downstream regulation of asexual development in Aspergillus fumigatus. Eukaryotic Cell. 5: 1585-1595.

Yu, J.-H. 2006. Heterotrimeric G protein signaling and RGSs in Aspergillus nidulans. Journal of Microbiology 44: 145-154.