Ivan V. Korendovych, Ph.D.

Education

Ph.D
Tufts University - 2006

M.S. & B.S. 
National Taras Shevchenko University of Kiev - 2000 & 1999

Postdoctoral Fellow
University of Pennsylvania Medical School - 2006 - 2011

Experience

Assistant Professor of Chemistry
Syracuse University - 2011 - 2017

Associate Professor of Chemistry
Syracuse University - 2017 - 2021

Professor of Chemistry and Associate Chair of the Chemistry Department
Syracuse University - 2021 - 2023

Professor and James R. Schofield Endowed Chair in Biochemistry
Baylor University - 2024 - Present

Research

Research in the Korendovych Lab focuses primarily on protein engineering, biocatalysis and chemical biology. Major research avenues include:

1. Metal containing amyloids are capable of catalyzing chemical reactions. We showed that small 7-residue amyloid-forming peptides designed from the first principles form efficient catalysts of ester hydrolysis with activity on par with those of the best small molecule and peptide catalysts reported to date. These results provide the first demonstration of substantial catalytic activity in simple peptide amyloids, and from a more practical perspective, open the door to the design of highly stable, robust, and easily varied enzyme-like catalysts. Moreover, by mixing different peptides we were able to observe synergistic interactions that increased activity even further. The ability to screen multiple stable arrangements of functional groups in a single fibril provides essentially limitless opportunities for high-throughput screening for functional activity by simply mixing peptides with different sequences. We showed that this catalytic system is capable of hydrolysis of highly challenging substrates such as paraoxon and can be easily expanded to redox reactions activating hydrogen peroxide AND oxygen.

a)  Rufo, C.M., Moroz, Y.S., Moroz, O.M., Stohr, J., Smith, T.A., Hu, Z., DeGrado, W.F., Korendovych, I.V.* (2014) Short peptides self-assemble to produce catalytic amyloids. Nature Chem., 6, 303-309. PMID: 24651196

b)  O.V. Makhlynets,^ P.M. Gosavi,# I.V. Korendovych* (2016) Short Peptides that Self-Assemble in the Presence of Copper are Capable of Oxygen Activation. Angew. Chem. Int. Ed., 55, 9017-9020 DOI: 10.1002/anie.201602480
 

2.  New method for de novo design of catalysts. Design of a new catalytic function in proteins, apart from its inherent practical value, is important for fundamental understanding of enzymatic activity. We developed a computationally inexpensive, minimalistic approach that focuses on introducing a single highly reactive residue into proteins to achieve catalysis. We show that this method can be easily generalized to various chemical transformations, such as retroaldol reaction, Kemp elimination and ester hydrolysis. Directed evolution allowed for further improvement of protein’s catalytic efficiency. Despite the seeming simplicity, the catalysts produced by this approach are highly active. AlleyCat7, an evolved catalyst of Kemp elimination, shows the kcat value that is only ca. 3-fold lower than that of the best evolved KE variant (KE59 R13-3/11H) and just ca. 5-fold higher than that of a catalytic antibody for Kemp elimination. The kcat/kuncat value for AlleyCat7 is more than 106. The catalytic efficiency of AlleyCatE, a stereoselective, allosterically regulated esterase, is higher than that of any previously reported de novo designed esterases and is on par with that of catalytic antibodies. The catalytic efficiency of AlleyCatR, an allosterically regulated retroaldolase is on par with that of other designed retroaldolases.
 

The simplicity of our design protocol should complement and expand the capabilities of current state-of-art approaches to protein design. Metal-based allostery allows for development of catalytically amplified sensors for metal ions. These results have fundamental implications for the evolution of catalysis as well as practical implications for the design of catalytically amplified sensors.

a)  Korendovych, I.V., Kulp, D.W., Wu, Y., Cheng, H., Roder, H., DeGrado, W.F. (2011) Design of a Switchable Eliminase. Proc. Natl. Acad. Sci. U.S.A., 108, 6823-6827. PMID: 21482808
 

b)  Moroz, O.V., Moroz, Y.S., Wu, Y., Olsen, A.B., Cheng, H., Mack, K.L., McLaughlin, J.M., Raymond, E.A., Zhezherya, K., Roder, H., Korendovych, I.V.* (2013) A Single Mutation in a Regulatory Protein Produces Evolvable Allosterically Regulated Catalyst of Unnatural Reaction. Angew. Chem. Int. Ed., 52, 6246-6249. PMID: 23630096

c)  Y.S. Moroz, T.T. Dunston, O.V. Makhlynets, O.V. Moroz, Y. Wu, J.H. Yoon, A.B. Olsen, J.M. McLaughlin, K.L. Mack, P.M. Gosavi, N.A.J. van Nuland, I.V. Korendovych* (2015) New Tricks For Old Proteins: Single Mutations in a Non-Enzymatic Protein Give Rise to Various Catalytic Activities. J. Am. Chem. Soc., 137, 14905-14911.  DOI: 10.1021/jacs.5b07812

d)  Raymond, E.A., Mack, K.L., Yoon, J.H., Moroz, O.V., Moroz Y.S., and Korendovych, I.V.  (2015) Design of an Allosterically Regulated Retroaldolase. Protein Sci., 24, 561-570. PMID: 25516403
 

3.  Development of a novel fluorescence probe. Intrinsic fluorescence of tryptophan provides invaluable information about protein folding, dynamics and structure. One of tryptophan’s strengths is dependence of its fluorescence on local microenvironment. The very same dependence is its Achilles’ heel: large shifts of quantum yields and fluorescence maxima positions could potentially change FRET and quenching efficiencies in fluorescence studies. We discovered that, unlike the previously developed tryptophan mimics, β-(1-Azulenyl)-L-Alanine (AzAla), a fluorescent pseudoisosteric analog of tryptophan has very small dependence on its local microenvironment. AzAla can be selectively excited at 342 nm, far away from most intrinsic fluorophores. AzAla shows simple single exponential fluorescence decay that allows for easy deconvolution of fluorescence lifetime data. We have incorporated AzAla in membrane and soluble peptides and studied their interactions with proteins. We demonstrated that weak environmental dependence of AzAla fluorescence allows for using even weak intrinsic quenchers, such as methionines and histidines to monitor protein-protein interactions while not perturbing them. These unique properties of AzAla together with its simple photophysics suggest great promise for this tryptophan mimic as a chemical biology tool. We have incorporated AzAla into the influenza A virus M2 proton channel without perturbing protein’s function. AzAla’s sensitivity to protonation state of the nearby histidines and the lack of environmental fluorescence dependence allowed us for direct and straightforward determination of histidine pKavalues in ion channels. In collaboration with the group of Prof. Jaap Broos (University of Groningen, the Netherlands) we used a tryptophan auxotroph (P1002) of the gram-positive bacterium Lactococcus lactis to incorporate AzAla into proteins in vivo. L. lactis is an attractive host for recombinant production of proteins including membrane proteins. Using this system we were able to incorporate AzAla into a model protein LmrR, a transcriptional regulatory protein in L. lactis, with 75-90 % efficiency.
 

a)  Moroz, Y.S., Binder, W., Nygren, P., Caputo, G.A., Korendovych, I.V.* (2013) Painting Proteins Blue: ß-(1-Azulenyl)-L-Alanine as a Tryptophan Mimic for Studying Protein-Protein interactions. Chem. Commun. 49, 490-492. PMID: 23207368
 

b) Ridgeway, Z., Picciano, A.L., Gosavi, P.M., Moroz, Y.S., Angevine, C.E., Chavis, A.E., Reiner, J., Korendovych* I.V., Caputo, G.A.* (2015) Functional Characterization of a Melittin Analog Containing a Non-natural Tryptophan Analog. Peptide Sci. 24, 561-570. PMID: 25670241
 

c) Gosavi, P.M., Moroz Y.S., Korendovych, I.V.* (2015) ß-(1-Azulenyl)-L-Alanine – a Functional Probe Studies of Membrane Proteins. Chem. Commun., 51, 5347-5350. PMID: 25645241
 

d)  J. Shao, I.V. Korendovych, J. Broos (2015) Biosynthetic Incorporation of the Azulene Moiety in Proteins with High Efficiency. Amino Acids, 47, 213-216. PMID: 25399056