Publications
* indicates joint first authorship
click on the article title for the PubMed abstract



Fitness landscapes and protein evolution

C. Goff*, E.-Y. Tsou*, J. D. Mehlhoff, M. Ostermeier
Environmental and mutational modulation of collateral fitness effects informs their mechanisms
Mol. Bio. Evol. 43: msag106 (2026) [full text]

S. Spisak, N. Ndahiro, M. J. Betenbaugh, M. Ostermeier
Deep mutational scanning of the AAV rep gene to assess effects on DNA packaging in Expi293F suspension culture
Biotechnol. Bioeng. 122: 3061-3072 (2025) [full text]

R. Weeks, M. Ostermeier
Fitness and functional landscapes of the E. coli RNase III gene rnc
Mol. Bio. Evol. 40: msad047 (2023) [full text]

J. D. Mehlhoff, M. Ostermeier
Genes vary greatly in their propensity for collateral fitness effects of mutations
Mol. Bio. Evol. 40: msad038 (2023) [full text]

J. D. Mehlhoff, F. W. Stearns, D. Rohm, B. Wang, E.-Y. Tsou, N. Dutta, M.-H. Hsiao, C. E. Gonzalez, A. F. Rubin, M. Ostermeier
Collateral fitness effects of mutations
Proc. Nat. Acad. Sci. USA 117: 11597-11607 (2020) [full text]  

J. D. Mehlhoff, M. Ostermeier
Biological fitness landscapes by deep mutational scanning
Methods Enzymol. 643: 203-224 (2020) [full text]

C. E. Gonzalez, P. Roberts, M. Ostermeier
Fitness effects of single amino acid insertions and deletions in TEM-1 β-lactamase
J. Mol. Biol., 431: 2320-2330 (2019) [full text]

C. E. Gonzalez, M. Ostermeier
Pervasive pairwise intragenic epistasis among sequential mutations in TEM-1 β-lactamase
J. Mol. Biol., 431: 1981-1992 (2019) [full text]

B. Steinberg, M. Ostermeier
Shifting fitness and epistatic landscapes reflect tradeoffs along an evolutionary pathway
J. Mol. Biol., 428: 2730–2743 (2016) [full text]

B. Steinberg, M. Ostermeier
Environmental changes bridge evolutionary valleys
Science Adv., 2(1): e1500921 (2016) [full text]

E. Firnberg, J. W. Labonte, J. J. Gray, M. Ostermeier
A comprehensive, high-resolution map of a gene's fitness landscape
Mol. Bio. Evol., 31: 1581-1592 (2014) [PDF]

E. Firnberg, M. Ostermeier
The genetic code constrains yet facilitates Darwinian evolution
Nucleic Acids Res., 41: 7420-7428 (2013) [full text]

E. Firnberg, M. Ostermeier
PFunkel: efficient, expansive, user-defined mutagenesis
PLoS One, 7(12): e52031 (2012) [PDF]

J. Liang, J. R. Kim, J. T. Boock, T. J. Mansell, M. Ostermeier
Ligand binding and allostery can emerge simultaneously
Protein Sci., 16: 929-937 (2007) [PDF]


Protein switches

S. Spisak, B. O'Brien, M. Ostermeier
A bacterial dual positive and negative selection system for dCas9 activity
PLoS One, 17(6): e0269270 (2022) [full text]

N. Y. Shelat, S. Parhi, M. Ostermeier
Development of a cancer-marker activated enzymatic switch from the herpes simplex virus thymidine kinase
Protein Eng. Des. Sel., 30: 95-103 (2017) [full text]

L. F. Ribeiro, T. D. Warren, M. Ostermeier
Construction of protein switches by domain insertion and directed evolution
Methods Mol. Biol., 1596: 43-55 (2017)

J. H. Choi, T. Xiong, M. Ostermeier
The interplay between effector binding and allostery in an engineered protein switch
Protein Sci., 25: 1605–1616 (2016) [full text]

L. F. Ribeiro, J. Tullman, N. Nicholes, S. R. B. Silva, D. S. Vieira, M. Ostermeier, R. J. Ward
A xylose-stimulated xylanase-xylose binding protein chimera created by random nonhomologous recombination
Biotechnol. Biofuels, 9: 119 (2016) [full text]

N. Nicholes, A. Date, P. Beaujean, P. Hauk, M. Kanwar, M. Ostermeier
Modular protein switches derived from antibody mimetic proteins
Protein Eng. Des. Sel., 29: 77-85 (2016) [full text]

J. Tullman*, N. Nicholes*, M. R. Dumont, L. F. Ribeiro, M. Ostermeier
Enzymatic protein switches built from paralogous input domains
Biotechnol. Bioeng., 113: 852-858 (2016) [full text]

J. H. Choi*, M. Zayats*, P. C. Searson, M. Ostermeier
Electrochemical activation of engineered protein switches
Biotechnol. Bioeng., 113: 453-456 (2016) [full text]

J. H. Choi, A. H. Laurent, V. J. Hilser, M. Ostermeier
Design of protein switches based on an ensemble model of allostery
Nature Commun., 6: 6968 (2015) [full text]

J. H. Choi, M. Ostermeier
Rational design of a fusion protein to exhibit disulfide-mediated logic gate behavior
ACS Synth. Biol., 4: 400-406 (2015) [full text]

L. F. Ribeiro, N. Nicholes, J. Tullman, L. F. C. Ribeiro, C. A. Fuzo, D. S. Vieira, G. P. Furtado, M. Ostermeier, and R. J. Ward
Insertion of a xylanase in xylose binding protein results in a xylose-stimulated xylanase
Biotechnol. Biofuels, 8: 118 (2015) [full text]

R. C. Wright, A. Khakhar, J. R. Eshleman, M. Ostermeier
Advancements in the development of HIF-1α-activated protein switches for use in enzyme prodrug therapy
PLoS One, 9(11): e114032 (2014) [full text]

G. Valdes, R. W. Schulte, M. Ostermeier, K. S. Iwamoto
The high-affinity maltose switch MBP317-347 has low affinity for glucose: implications for targeting tumors with metabolically-directed enzyme prodrug therapy
Chem. Biol. Drug Des., 83: 266-271 (2014)

J. H. Choi, A. San, M. Ostermeier
Non-allosteric enzyme switches possess larger effector-induced changes in thermodynamic stability than their non-switch analogs
Protein Sci., 22: 475-485 (2013) [PDF]

M. Kanwar, R. C. Wright, A. Date, J. Tullman, M. Ostermeier
Protein switch engineering by domain insertion
Methods Enzymol., 523: 369-388 (2013)

W. Ke, A. H. Laurent, M. D. Armstrong, Y. Chen, W. E. Smith, J. Liang, C. M. Wright, M. Ostermeier, F. van den Akker
Structure of an engineered β-lactamase maltose binding protein fusion protein: insights into heterotropic allosteric regulation
PLoS One, 7(6): e39168 (2012) [PDF]

R. A. Heins*, J. H. Choi*, T. Sohka, M. Ostermeier
In vitro recombination of non-homologous genes can result in gene fusions that confer a switching phenotype to cells
PLoS One, 6(11): e27302 (2011) [PDF]

C. M. Wright, R. C. Wright, J. R. Eshleman, M. Ostermeier
A protein therapeutic modality founded on molecular regulation
Proc. Nat. Acad. Sci. USA, 108: 16206-16211 (2011) [PDF]

J. Tullman, G. Guntas, M. Dumont, M. Ostermeier
Protein switches identified from diverse insertion libraries created using S1 nuclease digestion of supercoiled-form plasmid DNA
Biotechnol. Bioeng., 108: 2535-2543 (2011) [PDF]

M. Zayats, M. Kanwar, M. Ostermeier, P. C. Searson
Surface-tethered protein switches
Chem. Commun., 47: 3398-3400 (2011) [PDF]

C. M. Wright, A. Majumdar, J. R. Tolman, M. Ostermeier
NMR characterization of an engineered domain fusion between maltose binding protein and TEM1 β-lactamase provides insight into its structure and allosteric mechanism
Proteins, 78: 1423-1430 (2010) [PDF]

M. Ostermeier
Designing switchable enzymes
Curr. Opin. Struct. Biol., 19: 442-448 (2009) [PDF]

T. Sohka*, R. A. Heins*, R. M. Phelan, J. M. Greisler, C. A. Townsend, M. Ostermeier
An externally-tunable bacterial band-pass filter
Proc. Nat. Acad. Sci. USA, 106: 10135-10140 (2009) [PDF]

M. Berrondo, M. Ostermeier, J. J. Gray
Structure prediction of domain insertion proteins from structures of the individual domains
Structure, 16: 513-527 (2008) [PDF]

C. M. Wright, R. A. Heins, M. Ostermeier
As easy as flipping a switch?
Curr. Opin. Chem. Biol., 11, 342-346 (2007) [PDF]

J. Liang, J. R. Kim, J. T. Boock, T. J. Mansell, M. Ostermeier
Ligand binding and allostery can emerge simultaneously
Protein Sci., 16, 929-937 (2007) [PDF]

J. R. Kim, M. Ostermeier
Modulation of effector affinity by hinge region mutations also modulates switching activity in an engineered allosteric TEM1 β-lactamase
Arch. Biochem. Biophys., 446: 44-51 (2006) [PDF]

M. Ostermeier
Engineering allosteric protein switches by domain insertion
Protein Eng. Des. Sel., 18: 359-364 (2005) [PDF]

G. Guntas, T. J. Mansell, J. R. Kim, M. Ostermeier
Directed evolution of protein switches and their application to the creation of ligand-binding proteins
Proc. Nat. Acad. Sci. USA, 102: 11224-11229 (2005) [PDF]

G. Guntas, S. F. Mitchell, M. Ostermeier
A molecular switch created by in vitro recombination of non-homologous genes
Chem. Biol., 11: 1483-1487 (2004) [PDF]

G. Guntas, M. Ostermeier
Creation of an allosteric enzyme by domain insertion
J. Mol. Biol., 336: 263-273 (2004) [PDF]


Targeted DNA methylation

T. Xiong, D. Rohm, R. E. Workman, L. Roundtree, C. D. Novina, W. Timp, M. Ostermeier
Protein engineering strategies for improving the selective methylation of target CpG sites by a dCas9-directed cytosine methyltransferase in bacteria
PLoS One, 13(12): e0209408 (2018) [full text]

T. Xiong*, G. E. Meister*, R. E. Workman, N. C. Kato, M. J. Spellberg, T. Fulya, W. Timp, M. Ostermeier, C. D. Novina
Targeted DNA methylation in human cells using engineered dCas9-methyltransferases
Science Rep., 7: 6732 (2017) [full text]

B.Chaikind, M. Ostermeier
Directed evolution of improved zinc finger methyltransferases
PLoS One, 9(5): e96931 (2014) [full text]

B.Chaikind, K. P. Kilambi, J. J. Gray, M. Ostermeier
Targeted DNA methylation using an artificially bisected M.HhaI fused to zinc fingers
PLoS One, 7(9): e44852 (2012) [PDF]

G. E. Meister, S. Chandrasegaran, M. Ostermeier
Heterodimeric DNA methyltransferases as a platform for creating designer zinc finger methyltransferases for targeted DNA methylation in cells
Nucleic Acids Res., 38: 1749-1759 (2010) [PDF]

G. E. Meister, S. Chandrasegaran, M. Ostermeier
An engineered split M.HhaI-zinc finger fusion lacks the intended methyltransferase specificity
Biochem. Biophys. Res. Commun., 377: 226-230 (2008) [PDF]

S. Durai*, A. D. Bosley*, A. B. Abulencia, S. Chandrasegaran, M. Ostermeier
A bacterial one-hybrid selection system for interrogating zinc finger-DNA interactions
Comb. Chem. High Throughput Screen., 9: 301-311 (2007) [PDF]

W. Choe, S. Chandrasegaran, M. Ostermeier
Protein fragment complementation in M.HhaI DNA methyltransferase
Biochem. Biophys. Res. Commun., 334: 1233-1240 (2005) [PDF]


Gene circuits and synthetic biology

P. Hauk, R. Weeks, M. Ostermeier
A CRISPR/dCas9 system for assaying and selecting for RNase III activity in vivo in E. coli
CRISPR J. 6: 43-51 (2023) [full text]

S. Spisak, B. O'Brien, M. Ostermeier
A bacterial dual positive and negative selection system for dCas9 activity
PLoS One, 17(6): e0269270 (2022) [full text]

P. Hauk, K. Stephens, R. McKay, C. Virgile, H. Ueda, M. Ostermeier, K.-S. Ryu, H. Sintim, W. Bentley
Directed evolution of Escherichia coli quorum sensing promoter region of the lsrACDBFG operon: a tool for synthetic biology systems and protein expression
Nucleic Acids Res., 44: 10515-10525 (2016) [full text]

N. Y. Shelat, S. Parhi, M. Ostermeier
A positive selection for nucleoside kinases in E. coli
PLoS One, 11(9): e0162921 (2016) [full text]

J. H. Choi, M. Ostermeier
Rational design of a fusion protein to exhibit disulfide-mediated logic gate behavior
ACS Synth. Biol., 4: 400-406 (2015) [full text]

T. Sohka, R. A. Heins, M. Ostermeier
Morphogen-defined patterning of Escherichia coli enabled by an externally tunable band-pass filter
J. Biol. Eng., 3: 10 (2009) [PDF]

T. Sohka*, R. A. Heins*, R. M. Phelan, J. M. Greisler, C. A. Townsend, M. Ostermeier
An externally-tunable bacterial band-pass filter
Proc. Nat. Acad. Sci. USA, 106: 10135-10140 (2009) [PDF]

S. Durai*, A. D. Bosley*, A. B. Abulencia, S. Chandrasegaran, M. Ostermeier
A bacterial one-hybrid selection system for interrogating zinc finger-DNA interactions
Comb. Chem. High Throughput Screen., 9: 301-311 (2007) [PDF]


Gene therapy

S. Spisak, N. Ndahiro, M. J. Betenbaugh, M. Ostermeier
Deep mutational scanning of the AAV rep gene to assess effects on DNA packaging in Expi293F suspension culture
Biotechnol. Bioeng. , 122: 3061-3072 (2025) [full text]

T. Sagara, M. Debeljak, C. Hu, C. M. Wright, N. Anders, H. Liang, A. Maitra, M. Rudek, M. Ostermeier, J. R. Eshleman, Y. Matsushita
Successful gene therapy requires targeting the vast majority of cancer cells
Cancer Biology & Therapy, 21: 946-953 (2020)

T. D. Warren, K. Patel, J. L. Rivera, J. R. Eshleman, M. Ostermeier
Comprehensive mutagenesis on yeast cytosine deaminase yields improvements in 5-fluorocytosine toxicity in HT1080 cells
AIChE Journal, 66: e16688 (2020) [full text]

T. D. Warren, K. Patel, J. R. Eshleman, M. Ostermeier
Protein-programmed accumulation of yeast cytosine deaminase in cancer cells in response to mock-hypoxia
ACS Synth. Biol., 17: 948-954 (2019) [full text]

N. Y. Shelat, S. Parhi, M. Ostermeier
Development of a cancer-marker activated enzymatic switch from the herpes simplex virus thymidine kinase
Protein Eng. Des. Sel., 30: 95-103 (2017) [full text]

N. Y. Shelat, S. Parhi, M. Ostermeier
A positive selection for nucleoside kinases in E. coli
PLoS One, 11(9): e0162921 (2016) [full text]

R. C. Wright, A. Khakhar, J. R. Eshleman, M. Ostermeier
Advancements in the development of HIF-1α-activated protein switches for use in enzyme prodrug therapy
PLoS One, 9(11): e114032 (2014) [full text]

J. H. Russell, M. Ostermeier
The thymidylate kinase genes from Mycobacterium tuberculosis and methicillin resistant Staphylococcus auerus confer 3'-azido-3'-deoxythymidine resistance to Escherichia coli
FEMS Microbiol. Lett., 361: 158-165 (2014) [full text]

C. M. Wright, R. C. Wright, J. R. Eshleman, M. Ostermeier
A protein therapeutic modality founded on molecular regulation
Proc. Nat. Acad. Sci. USA, 108: 16206-16211 (2011) [PDF]

K. Hida, S. Y. Won, G. Di Pasquale, J. Hanes, J. A. Chiorini, M. Ostermeier
Sites in the AAV5 capsid tolerant to deletions and tandem duplications
Arch. Biochem. Biophys., 496: 1-8 (2010) [PDF]

R. M. Phelan, M. Ostermeier, C. A. Townsend
Design and synthesis of a β-lactamase activated 5-fluorouracil prodrug
Bioorg. Med. Chem. Let., 19: 1261-1263 (2009) [PDF]

K. Hida, J. Hanes, M. Ostermeier
Directed evolution for drug and nucleic acid delivery
Adv. Drug Deliv. Rev., 59,: 1562-1578 (2007) [PDF]


Miscellaneous protein engineering

M. Martins, A. M. D. Santos, C. H. S. da Costa, S. W. Canner, M. Chungyoun, J. J. Gray, M. S. Skaf, M. Ostermeier, R. Goldbeck
Thermostability enhancement of GH 62 ɑ-l-arabinofuranosidase by directed evolution and rational design
J. Agric. Food Chem., 72: 4225-4236 (2024) [full text]

E. Firnberg, M. Ostermeier
PFunkel: efficient, expansive, user-defined mutagenesis
PLoS One, 7(12): e52031 (2012) [PDF]

G.Guntas, M. Kanwar, M. Ostermeier
Circular permutation in the Ω-loop of TEM1 β-lactamase results in improved activity and altered substrate specificity
PLoS One, 7(4): e35998 (2012) [PDF]

C. Kim, B. Pierre, M. Ostermeier, L. L. Looger, J. R. Kim
Enzyme stabilization by domain insertion into a thermophilic protein
Protein Eng. Des. Sel., 22,: 615-623 (2009) [PDF]

G. E. Meister, M. Kanwar, M. Ostermeier
Circular permutation of proteins
In: S. Lutz and U. Bornscheuer (eds) Protein Engineering Handbook, Wiley (2009)

M. Ostermeier
Beyond cataloging the Library of Babel
Chem. Biol., 14: 237-238 (2007) [PDF]

D. Paschon, Z. S. Patel, M. Ostermeier
Enhanced catalytic efficiency of aminoglycoside phosphotransferase (3')-IIa achieved through protein fragmentation and reassembly
J. Mol. Biol., 353: 26-37 (2005) [PDF]

W. Choe, S. Chandrasegaran, M. Ostermeier
Protein fragment complementation in M.HhaI DNA methyltransferase
Biochem. Biophys. Res. Commun., 334: 1233-1240 (2005) [PDF]

A. D. Bosley, M. Ostermeier
Mathematical expressions useful in the construction, description and evaluation of protein libraries
Biomol. Eng., 22: 57-61 (2005) [PDF]

D. E. Paschon, M. Ostermeier
Construction of protein fragment complementation libraries using incremental truncation
Methods Enzymol., 388: 103-116 (2004) [PDF]

M. Ostermeier
Synthetic gene libraries: in search of the optimal diversity
Trends Biotechnol., 21: 244-247 (2003) [PDF]

M. Ostermeier
Theoretical distribution of truncation lengths in incremental truncation libraries
Biotechnol. Bioeng., 82: 564-577 (2003) [PDF]

M. Ostermeier, S. Lutz
The creation of ITCHY hybrid protein libraries
Methods Mol. Biol., 231: 129-142 (2003) [PDF]

S. Lutz, M. Ostermeier
Preparation of SCRATCHY hybrid protein libraries: size- and in-frame selection of nucleic acid sequences
Methods Mol. Biol., 231: 143-152 (2003) [PDF]


Miscellaneous

L. Ribeiro, C. Chelius, K. Boppidi, N. Naik, S. Hossain, J. Ramsey, J. Kumar, L. Riberio, M. Ostermeier, B. Tran, Y. Goo, L. deAssis, M. Ulas, Ö. Bayram, G. Goldman, S. Lincoln, R. Srivastava, S. Harris, M. Marten
Comprehensive analysis of A. nidulans PKA phosphorylome identifies a novel mode of CreA regulation
mBio, 10: e02825-18 (2019)

C.-C. Ko, M. Ostermeier, S.-C. Lin
Dual column approach for the purification of zinc finger proteins by immobilized metal affinity chromatography
Process Biochem., 73: 204 (2018) [full text]

J. P. Fuenzalida, P. K. Nareddy, I. Moreno-Villoslada, B. M. Moerschbacher, M. J. Swamy, S. Pan, M. Ostermeier, F. M. Goycoolea
On the role of alginate structure in complexing with lysozyme and application for enzyme delivery.
Food Hydrocolloids, 53: 239-248 (2016) [full text]

L. S.-L. Cheung*, D. J. Shea*, N. Nicholes, A. Date, M. Ostermeier, K. Konstantopoulos
Characterization of monobody scaffold interactions with ligand via force spectroscopy and steered molecular dynamics
Sci. Rep., 5: 8247 (2015) [full text]

L. S.-L. Cheung*, M. Kanwar*, M. Ostermeier, K. Konstantopoulos
A hot-spot motif characterizes the interface between a designed ankyrin-repeat protein and its target ligand
Biophys. J., 102: 407-416 (2012) [PDF]

M. Zayats, M. Kanwar, M. Ostermeier, P. C. Searson.
Molecular Imprinting of maltose binding protein: tuning protein recognition at the molecular level
Macromolecules, 44: 3966-3972 (2011) [PDF]


Other publications by Marc Ostermeier

M. Ostermeier, S. Lutz, S. J. Benkovic
Generation of protein fragment libraries by incremental truncation
In: Golemis, E.A. (ed) Protein-Protein Interactions: A Molecular Cloning Manual, Cold Spring Harbor Laboratory Press (Cold Spring Harbor, NY, 2002).

S. Lutz, M. Ostermeier, G. L. Moore, C. D. Maranas, S. J. Benkovic
Creating multiple-crossover DNA libraries independent of sequence identity
Proc. Nat. Acad. Sci. USA, 98: 11248-11253 (2001) [PDF]

S. Lutz, M. Ostermeier, S. J. Benkovic
Rapid generation of incremental truncation libraries for protein engineering using alpha-phosphothioate nucleotides
Nucleic Acids Res., 29: e16 (2001) [PDF]

M. Ostermeier, S. J. Benkovic
Construction of hybrid gene libraries involving the circular permutation of DNA
Biotechnology Letters, 23: 303-310 (2001) [PDF]

M. Ostermeier, S. J. Benkovic
Evolution of protein function by domain swapping
Advances in Protein Chemistry, 55: 29-77 (2000) [PDF]

M. Ostermeier, S. J. Benkovic
A two-phagemid system for the creation of non-phage displayed antibody libraries approaching one trillion members
J. Immunol. Methods, 237: 175-186 (2000) [PDF]

M. Ostermeier, J. H. Shim, S. J. Benkovic
A combinatorial approach to hybrid enzymes independent of DNA homology
Nature Biotechnol., 17: 1205-1209 (1999) [PDF]

M. Ostermeier, A. E. Nixon, S. J. Benkovic
Incremental truncation as a strategy in the engineering of novel catalysts
Bioorg. Med. Chem., 7: 2139-2144 (1999) [PDF]

M. Ostermeier, S. J. Benkovic
Finding Cinderella's slipper - proteins that fit
Nature Biotechnol., 17: 639-640 (1999) [PDF]

M. Ostermeier, A. E. Nixon, J. H. Shim, S. J. Benkovic
Combinatorial protein engineering by incremental truncation
Proc. Nat. Acad. Sci. USA, 96: 3562-3567 (1999) [PDF]

A.E. Nixon, M. Ostermeier, S. J. Benkovic
Hybrid enzymes: manipulating enzyme design
Trends Biotechnol., 16: 258-264 (1998) [PDF]

M. Ostermeier, K. De Sutter, G. Georgiou
Eukaryotic protein disulfide isomerase complements Escherichia coli dsbA mutants and increases the yield of a heterologously secreted protein with disulfide bonds
J. Biol. Chem., 271: 10616-10622 (1996) [PDF]

G. Georgiou, P. Valax, M. Ostermeier, M., P. M. Horowitz
Folding and aggregation of TEM β-lactamase: analogies with the formation of inclusion bodies in Escherichia coli
Prot. Sci., 3: 1953-1960 (1994) [PDF]

M. Ostermeier, M., G. Georgiou
The folding of bovine pancreatic trypsin inhibitor in the Escherichia coli periplasm
J. Biol. Chem., 269: 21072-21077 (1994) [PDF]