Constance Bailey

Assistant Professor

Research

The focus of the Bailey laboratory is to access chemical transformations through biological means, both through engineering enzymes as biocatalysts as well as the organisms that host engineered biosynthetic pathways. Specifically, we seek to apply natural product biosynthetic enzymes, primarily polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs), to generate valuable molecules such pharmaceuticals, pharmaceutical intermediates, commodity chemicals, and specialty chemicals. PKSs and NRPSs are multi-domain enzymatic megasynthases that undergo sequential decarboxylative condensations followed by reductive processing. Because of their modular nature, PKSs and NRPSs can generate endless variations of metabolites that differ by the degree of branching and reduction of the carbon scaffold. The interdisciplinary research in my group harnesses intellectual approaches from physical organic chemistry and enzymology to tune biocatalytic transformations. It also applies metabolic engineering to create strains to produce these chemicals. 

Biography

Constance Bailey began her academic career at Reed College, where she pursued research in natural products biochemistry as well as organic synthesis. Under the mentorship of Prof. Adrian Keatinge-Clay at UT Austin, her doctoral research focused on the biocatalytic applications of polyketide synthase enzymes. Following her Ph.D. she was an NIH Postdoctoral Fellow in the laboratory of Prof. Jay Keasling at UC Berkeley and Lawrence Berkeley National Laboratory, focusing on developing synthetic biology applications of polyketide synthases as a "plug and play" platform to generate a range of valuable chemicals.

Education

B.A. Reed College (2010)

Ph.D. University of Texas at Austin (2015)

NIH Postdoctoral Fellowship UC Berkeley, Lawrence Berkeley National Laboratory and the Joint BioEnergy Institute (2016-2018)

Awards and Recognitions

NIH Ruth L. Kirschstein National Research Service Award (2018)

Discussion Leader for Keynote Session, Gordon Research Seminar on Natural Products and Bioactive Compounds (2017)

University of Texas at Austin GK-12 Graduate Fellowship (2013)

Commendation for Academic Excellence, Reed College (2010)

Publications

Drufva, E.E.; Sword, T.T.; Bailey, C.B. Metabolic Engineering of Actinomycetes for Natural Product Discovery. Actinomyces: Diversity, Ecology, and Drug Discovery.  Rai, Ravishankar and Bai A, Jamuna (Eds.) Springer Singapore, 2022, 262-307. 

Drufva, E.E.; Spengler, N.R.; Hix, E.G.; Bailey, C.B. Site Directed Mutagenesis of Modular Polyketide Synthase Ketoreducatse Domains         for Altered Steroechemical Control. ChemBioChem. 2020, ChemBioChem, 2020, 6, 1122. 

Drufva, E.E.; Hix, E.G. Bailey, C.B. Site Directed Mutagenesis as a Precision Tool to Enable Synthetic Biology with           Engineered Polyketide Synthases. Synthetic and Systems Biotechnol. 2020, 5, 62. 

Zargar, A.; Lal, R.; Valencia, L.; Wang, J.; Backman T.W.H.; Cruz-Morales, P.; Kothari, A.; Werts, M.; Wong, A.R.; Bailey, C.B.; Loubat, A.; Yuzhong, L., Benites, V.; Chang, S.; Hernadez, A.C.; Barajas, J.F.; Thompson, M.G.; Barcelos, C.; Anayah, R.; Garcia Martin, H.; Mukhopaday, A.; Baidoo, E.; Katz, L.; Keasling, J.D. Chemoinformatic-Guided Engineering of Polyketide Synthases. J. Am. Chem. Soc. 2020, 142, 9896. 

Yuzawa, S.; Bailey, C.B.; Fuji, T.; Jocic, R.; Barajas, J.F.; Benites, V.T.; Baidoo, E.E.; Chen, Y.; Petzold, C.J.; Katz, L.; Keasling, J.D. Heterologous Gene Expression of N-Terminally Truncated Variants of LipPKS1 Suggests a Functionally Critical Structural Motif in the N-terminus of Modular Polyketide Synthases. ACS Chem. Biol. 2017, 12, 2725. 

Eng, C.H.;* Backman, T.W.H.;* Bailey, C.B.; Magnan, C.; García Martín, H.; Katz, L.; Baldi, P.; Keasling, J.D. ClusterCAD: a Computational Platform for Type I Polyketide Synthase Design. Nucl. Acid. Res. 2017, gx893. *Authors contributed equally 

Barajas, J.F.;* Blake-Hedges, J.M.;* Bailey, C.B.;* Curran S.; Keasling, J.D. Engineered Polyketides: Synergy Between Protein and Host Level Engineering. Synthetic and Systems Biotechnol. 2017, 166, 147. *Authors contributed equally 

Wagner, D.T.;* Zeng, J.;* Bailey, C.B.;* Gay, D.C.; Yuan, F.; Manion, H.R.; Keatinge-Clay, A.T. Structural and Functional Trends in Dehydrating Bimodules from trans-Acyltransferase Polyketide Synthases. Structure. 2017, 25, 1. *Authors contributed equally 

Zargar, A.; Bailey, C.B.; Haushalter, R.W.; Eiben, C.B., Katz, L; Keasling, J.D. Leveraging Microbial Biosynthetic Pathways for the Generation of ‘Drop In’ Biofuels. Curr. Opin. Biotechnol. 2017, 45, 156. 

Bailey, C.B.; Pasman, M.E.; Keatinge-Clay, A.T. Substrate Structure-Activity Relationships Guide Rational Engineering of Stereocontrol in Modular Polyketide Synthase Ketoreductases. ChemComm. 2016, 52, 792.