Dr. Ping Li

Biography

Research Overview

Using enzymology, synthetic organic chemistry, and molecular biology as major tools to study and manipulate biologically important enzymes/proteins. Currently, I have three projects in my lab.

1. Polyhydroxyalkanoate (PHA) biosynthesis, regulation, and utilization.
   PHAs are carbon storage polymers produced by a variety of bacteria under conditions that limit nutrients except for carbon. The environmentally friendly PHA bioplastics are considered as an ideal alternative to petroleum-derived plastics that are non-biodegradable. Our goal is to understand PHA homeostasis at the molecular level such that metabolic- and protein-engineering in bacteria can be performed to produce PHA polymers economically. Moreover, study of PHA production can serve as a paradigm to understand widespread template-independent polymerizations where the mechanism remains enigmatic.
2. Bacterial enzymes involved in lignin degradation.
   Lignin is a recalcitrant polymer consisting of various phenylpropane-based monomers linked together by C-C and C-O-C bonds, which is the most abundant renewable carbon source on earth next to cellulose. The cost of lignin degradation has been a major indicator for the competitiveness of biofuels vs. petroleum-based gasoline. It is well known that fungus contains a series of redox metalloenzymes that can efficiently degrade lignin. However, until now they have not been used at industrial scales due to difficulties in modulation of fungal genetics and production of fungal proteins. Therefore, there is a paradigm shift to seek for bacterial enzymes for lignin degradation. Our goal is to identify and develop them into a system that can be used to process lignin degradation economically at large scales.
3. Protein methyltransferases in epigenetics.
   Methylation is one of commonly observed protein posttranslational modifications that play important roles in signaling network and epigenetic regulation. Defects in the methylation have been linked to various diseases including cancers, neurological disorders, and abnormalities in development. Aside from protein lysine and arginine methyltransferases, a new type of protein methyltransferases, α-N-terminal RCC1 methyltransferases (NRMTs), was recently discovered in eukaryotes and human. Limited study of NRMTs suggests that they may be linked to cancers. Our goal is to identify the processes and/or targets involving NRMT for potential cancer therapy.

Selected publications

1. Zhou, Q., Wu, W., Jia, K., Qi, G., Sun, X.S., Li, P.* Design and characterization of PROTAC degraders specific to protein N-terminal methyltransferase 1. Eur. J. Med. Chem. 2022, 244: 114830, DOI: 10.1016/j.ejmech.2022.114830.
2. Li, Q., Qi, G., Lutter, D., Beard, W., Souza, C.R., Highland, M.A., Wu, W., Li, P., Zhang, Y., Atala, A., Sun, X.S. Injectable peptide hydrogel encapsulation of mesenchymal stem cells improved viability, stemness, anti-inflammatory effects, and early stage wound healing. Biomolecules 2022, 12: 1317, DOI: 10.3390/biom12091317.
3. Pradyawong, S., Shrestha, R., Li, P., Sun, X.S., and Wang, D. Effect of pH and pH-shifting on lignin–protein interaction and properties of lignin-protein polymers. J. Polym. Environ. 2022, 30, 1908-1919, DOI: 10.1007/s10924-021-02319-8.
4. Shrestha, R., Jia K., Khadka S., Eltis L.D., and Li P.* Mechanistic insights into DyPB from Rhodococcus jostii RHA1 via kinetic characterization, ACS Catal. 2021, 11, 5486-5495, DOI: 10.1021/cascatal.1c00703.
5. Jia, K., Huang, G., Wu, W., Shrestha, R., Wu, B., Xiong, Y., and Li, P.* In vivo methylation of OLA1 revealed by activity-based target profiling of NTMT1, Chem. Sci. 2019, 10, 8094-8099, DOI: 10.1039/C9SC02550B.
   *Highlighted as a back-cover article .
6. Shrestha, R., Huang, G., Meekins, D., Geisbrecht, B.V., and Li, P.* Mechanistic insights into dye-decolorizing peroxidase revealed by solvent isotope and viscosity effects, ACS Catal. 2017, 7, 6352-6364, DOI: 10.1021/acscatal.7b01861.
7. Huang, G., Shrestha, R., Jia, K., Geisbrecht, B.V., and Li, P.* Enantioselective synthesis of dilignol model compounds and their stereodiscrimination study with a dye-decolorizing peroxidase, Org. Lett., 2017, 19, 1820-1823, DOI: 10.1021/acs.orglett.7b00587.
8. Shrestha, R., Chen, X., Ramyar, K. X., Hayati, Z., Carlson, E. A., Bossmann, S. H., Song, L., Geisbrecht, B.V., and Li, P.* Identification of surface-exposed protein radicals and a substrate oxidation site in A-class dye-decolorizing peroxidase from Thermomonospora curvata, ACS Catal. 2016, 6, 8036-8047, DOI: 10.1021/acscatal.6b01952.
9. Jia, K., Cao, R., Hua, D.H., and Li, P.* Study of class I and class III polyhydroxyalkanoate (PHA) synthases with substrates containing a modified side chain, Biomacromolecules 2016, 17, 1477-1485, DOI: 10.1021/acs.biomac.6b00082.
10. Chen, C., Shrestha, R., Jia, K., Gao, P.F., Geisbrecht, B.V., Bossmann, S. H., Shi, J., and Li, P.* Characterization of dye-decolorizing peroxidase (DyP) from Thermomonospora curvata reveals unique catalytic properties of A-type DyPs, J. Biol. Chem. 2015, 290, 23447-23463, DOI: 10.1074/jbc.M115.658807.
11. Chen, C., Cao, R., Shrestha, R., Ward, C., Katz, B.B., Fischer, C.J., Tomich, J.M. and Li, P.* Trapping of intermediates with substrate analog HBOCoA in the polymerizations catalyzed by class III polyhydroxybutyrate (PHB) synthase from Allochromatium Vinosum, ACS Chem. Biol. 2015, 10, 1330-1339, DOI: 10.1021/cb5009958.
12. Zhang, W., Chen, C., Cao, R., Maurmann, L., and Li, P.* Inhibitors to polyhydroxyalkanoate (PHA) synthases: synthesis, molecular docking, and implications, ChemBioChem 2015, 16, 156-166, DOI: 10.1002/cbic.201402380.
13. Zhang, W., Shrestha, R., Buckley, R. M., Jewell, J., Bossmann, S. H., Stubbe, J., and Li, P.* Mechanistic insight with HBCH₂CoA as a probe to polyhydroxybutyrate (PHB) synthases, ACS Chem. Biol. 2014, 9, 1773-1779, DOI: 10.1021/cb5002735.