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Jeremy Lohman

Jeremy Lohman Profile Picture

Assistant Professor of Biochemistry
Ph.D. - 2007 - The University of Oregon


Contact Info:

jlohman@purdue.edu


Training Group(s):
Biomolecular Structure and Biophysics


Current Research Interests:

Natural products are one of our best sources of drugs and drug leads. Natural products from bacteria and fungi have the benefit of being supplied through fermentation, in contrast to sources such as plants and sponges that suffer from slow-growth and ecological concerns such as overharvesting. Natural products exist to benefit their hosts, as such some natural product drugs are not ideal for human use. Synthetic derivatives of these natural products often have superior activity, but cost significantly more to produce. Therefore finding methods to generate natural product derivatives through fermentation is an important goal. Combinatorial biosynthesis is the process of creating natural products through the genetic engineering of producing organisms to generate natural product derivatives. Currently, the easiest method for producing natural product derivatives is through deletion of genes encoding enzymes that add functionality to a natural product. However, many enzymes are essential to building the core of a natural product, limiting the number of derivatives created through gene deletion. Another approach is to add enzymes to the pathway or to alter the substrate specificity of enzymes within the biosynthetic pathway. The major hurdle to the second approach is a lack in our current understanding of the structure-function relationships of these enzymes. Our lab is seeking to understand the sequence-structure-function relationships in families of biosynthetic enzymes, so that our knowledge will be of use in engineering multiple biosynthetic pathways. Through reverse engineering the sequence-structure-function relationships of biosynthetic enzyme families we will engineer new substrate specificity into enzymes within pathways, and thus enable true combinatorial biosynthesis. Using bioinformatics, x-ray crystallography and enzymology together, we will discover how sequence-structure-function is related within families of biosynthetic enzymes. We will have genes synthesized that encode proteins with engineered substrate specificity and probe their activities in vitro. Finally using genetics we will introduce the engineered synthetic genes into natural product producers to isolate natural product derivatives.



Selected Publications:

Childs-Disney, J., Yildirim, I., Park, H., Lohman, J. R., Guan, L., Tran, T., . . . Disney, M. (2014). Structure of the Myotonic Dystrophy Type 2 RNA and Designed Small Molecules That Reduce Toxicity. ACS Chem Biol, 9, 538-550. Retrieved from http://pubs.acs.org/doi/pdf/10.1021/cb4007387

Lohman, J. R., Ma, M., Cuff, M. E., Bigelow, L., Bearden, J., Babnigg, G., . . . Shen, B. (2013). The Crystal Structure of BlmI as a Model for Type-II Nonribosomal Peptide Synthetase Peptidyl Carrier Proteins. Proteins-Structure Function and Bioinformatics, ..Huang, S. X., Lohman, J. R., Huang, T., & Shen, B. (2013). A new member of the 4-methylideneimidazole-5-one-containing aminomutase family from the enediyne kedarcidin biosynthetic pathway. Proc. Natl. Acad. Sci. U.S.A., 110, 8069-8074. Retrieved from http://www.pnas.org/content/110/20/8069

Ma, M., Kwong, T., Lim, S. K., Ju, J., Lohman, J. R., & Shen, B. (2013). Post-polyketide synthase steps in iso-migrastatin biosynthesis, featuring tailoring enzymes with broad substrate specificity. J. Am. Chem. Soc., 135, 2489-2492. Retrieved from http://pubs.acs.org/doi/ipdf/10.1021/ja4002635

Lohman, J. R., Huang, S. X., Horsman, G. P., Dilfer, P. E., Huang, T., Chen, Y. H., . . . Shen, B. (2013). Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics. Mol. BioSyst., 9, 478-491. Retrieved from http://pubs.rsc.org/en/content/articlepdf/2013/mb/c3mb25523a

Lohman, J. R., Bingman, C. A., Phillips Jr., G. N., & Shen, B. (2013). Structure of the bifunctional acyltransferase/decarboxylase LnmK from the leinamycin biosynthetic pathway revealing novel activity for a double-hot-dog fold. Biochemistry, 52, 902-911. Retrieved from http://pubs.acs.org/doi/ipdf/10.1021/bi301652y

Lohman, J. R., & Shen, B. (2012). 4-Methylideneimidazole-5-one-containing aminomutases in enediyne biosynthesis. In Methods Enzymol (Vol. 516, pp. 299-319). Retrieved from http://dx.doi.org/10.1016/B978-0-12-394291-3.00007-1

Coonrod, L. A., Lohman, J. R., & Berglund, J. A. (2013). Utilizing the GAAA tetraloop/receptor to facilitate crystal packing and structure determination of a CUG RNA helix. Biochemistry, 51, 8330-8337. Retrieved from http://pubs.acs.org/doi/ipdf/10.1021/bi300829w

Yin, M., Lu, T., Zhao, L. X., Chen, Y. H., Huang, X. S., Lohman, J. R., . . . Shen, B. (2011). The missing C-17 O-Methyltransferase in Geldanamycin Biosynthesis. Org. Lett., 13, 3726-3729. Retrieved from http://pubs.acs.org/doi/ipdf/10.1021/ol201383w

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