2026

Bista, R., Zhang, J., Stegall, H., Tran, T.-H., Jaegy, H., Keatinge-Clay, A.T. (2026). Exploring the limits of polyketide synthase engineering through swapping rapamycin modules into the pikromycin synthase. Nat. Chem., submitted.

Zhang, J., Keatinge-Clay, A.T. (2026). Rapid biocatalysis of stereocomplex polyketides by in vitro reconstituted assembly lines. Nat. Catal., submitted.

Zhang, J., Bista, R., Keatinge-Clay, A.T. (2026). Engineered modular polyketide synthases elucidate how enoylreductases collaborate with acyl carrier proteins and ketosynthases to set stereocenters. J. Am Chem. Soc., in revision.

Kudo, K., Hashimoto, T., Awakawa, T., Zhang, L., Nishimura, T., Hashimoto, J., Kozone, I., Kagaya, N., Suenaga, H., Keatinge-Clay, A.T., Abe, I., Shin-ya, K. (2026) Skeletal editing via multi-step engineering of a modular polyketide synthase. Nat. Commun., in revision.

Miyazawa, T., Keatinge-Clay, A.T. (2026). Refactoring the pikromycin synthase for the modular biosynthesis of macrolide antibiotics in E. coli. Nat. Synth., in revision.

2025

Hoogerbrugge, G., Keatinge-Clay, A.T., Marcotte., E.M. (2025). Serendipity and the slime mold: a visual survey of megadalton protein assemblies reveals the structure of the polyketide synthase Pks16. Mol. Cell. Proteom. Link

Wang, Z.-C., Stegall, H., Miyazawa, T., Keatinge-Clay, A.T. (2025). A CRISPR-Cas9 system for knock-out and knock-in of high molecular weight DNA enables module-swapping of the pikromycin synthase in its native host. Microb. Cell Fact. 24:125 Link

Ray, K.A., Lin, S.N., Keatinge-Clay, A.T. (2025). Distinct acyl carrier protein docking sites help mediate the opposite stereoselectivities of A- and B-type modular polyketide synthase ketoreductases. Biochemistry 64:1136-1145 Link

2024

Ray, K.A., Lutgens, J.D., Bista, R., Zhang, J., Desai, R.R., Hirsch, M., Miyazawa, T., Cordova, A., Keatinge-Clay, A.T. (2024). Assessing and harnessing updated polyketide synthase modules through combinatorial engineering. Nat. Commun. 15:6485 Link

Hirsch, M., Desai, R.R., Annaswamy, S., Keatinge-Clay, A.T. (2024). Mutagenesis supports AlphaFold prediction of how modular polyketide synthase acyl carrier proteins dock with downstream ketosynthases. Proteins doi:10.1002/prot.26733 Link

Ray, K.A., Saif, N., Keatinge-Clay, A.T. (2024). Modular polyketide synthase ketosynthases collaborate with upstream dehydratases to install double bonds. Chem. Comm. 60:8712-8715. Link

2023

Zhang, J., Bista, R., Miyazawa, T., Keatinge-Clay, A.T. (2023) Boosting titers of engineered triketide and tetraketide synthases to record levels through T7 promoter tuning. Metab. Eng. 78:93-98. Link

Moor, S.R., Howard, J.R., Herrera, B.T., McVeigh, M.S., Marini, F., Keatinge-Clay, A.T., Anslyn, E.V. (2023). Determination of enantiomeric excess and diastereomeric excess via optical methods. Application to alpha-methyl-beta-hydroxy-carboxylic acids. Org. Chem. Front. 10: 1386-1392. Link

Keatinge-Clay, A.T., Miyazawa, T., Zhang, J., Ray, K.A., Lutgens, J.D., Bista, R., Lin, S.N. (2023). Crystal structures reveal the framework of cis-acyltransferase modular polyketide synthases. bioRxiv. doi: 10.1101/2023.02.11.528132. Link

2022

Zhou, W., Alharbi, H.A., Hummingbird, E., Keatinge-Clay, A.T., Mahmud. T. (2022). Functional studies and revision of the NFAT-133/TM-123 biosynthetic pathway in Streptomyces pactum. ACS Chem. Biol. 17:2039-2045. Link

Dickinson, M.S., Miyazawa, T., McCool, R.S., Keatinge-Clay, A.T. (2022). Priming enzymes from the pikromycin synthase reveal how assembly line ketosynthases catalyze carbon-carbon chemistry. Structure 30:1331-1339. Link

2021

Choi, S.-h., Jeon, B., Kim, N., Wu, H.-H., Ko, T.-P., Ruszczycky, M.W., Isiorho, E.A., Liu, Y.-n., Keatinge-Clay, A.T., Tsai, M.-D., Liu, H.-w. (2021). Evidence for an enzyme-catalyzed Rauhut-Currier reaction during the biosynthesis of Spinosyn A. J. Am. Chem. Soc. 143: 20291-20295. Link

Hirsch, M., Fitzgerald, B.J., Keatinge-Clay, A.T. (2021). How cis-acyltransferase assembly-line ketosynthases gatekeep for processed polyketide intermediates. ACS Chem. Biol. 16:2515-2526. Link

Miyazawa, T., Fitzgerald, B.J., Keatinge-Clay, A.T. (2021). Preparative production of an enantiomeric pair by engineered polyketide synthases. Chem. Commun. 57:8762-8765. Link

Hirsch, M., Kumru,K., Desai, R.R., Fitzgerald, B.J., Miyazawa, T. Ray, K.A., Saif, N., Spears, S., Keatinge-Clay, A.T. (2021). Insights into modular polyketide synthase loops aided by repetitive sequences. Proteins 89:1099-1110. Link

2020

Miyazawa, T., Hirsch, M., Zhang, Z., Keatinge-Clay, A.T. (2020). An in vitro platform for engineering and harnessing modular polyketide synthases. Nat. Commun. 1:80. Link

2019

Zhang, Z., Cepeda, A.J., Robles, M.L., Hirsch, M., Kumru, K., Zhou, J.A., Keatinge-Clay, A.T. (2019). General chemoenzymatic route to two-stereocenter triketides employing assembly line ketoreductases. Chem. Commun. 56:157-160. Link

Meinke, J.L., Simon, A.J., Wagner, D.T., Morrow, B.R., You, S., Ellington, A.D., Keatinge-Clay, A.T. (2019). Employing 25-residue docking motifs from modular polyketide synthases as orthogonal protein connectors. ACS Synthetic Biology 8:2017-2024. Link

Valencia, L.E., Zhang, Z., Cepeda, A.J., Keatinge-Clay, A.T. (2019). Seven-enzyme in vitro cascade to (3R)-3-hydroxybutyryl-CoA. Org. Biomol. Chem. 17:1375-1378. Link

2018

Meinke, J.L., M. Mehaffey, M.R., Wagner, D.T., Sun, N., Zhang, Z., Brodbelt, J.S., Keatinge-Clay, A.T. (2018). Structural and functional studies of a gem-dimethylating methyltransferase from a trans-acyltransferase assembly line. ACS Chem. Biol. 13:3306-3314. Link

Liu, C., Yuan, M., Xu, X., Wang, L., Keatinge-Clay, A.T., Deng, Z., Lin, S., Zheng, J. (2018). Stereochemical insights from substrate-bound structures of ketoreductases from modular polyketide synthases. J. Struct. Biol. 203:135-141. Link

Vander Wood, D.A., Keatinge-Clay, A.T. (2018). The modules of trans-acyltransferase assembly lines redefined with a central acyl carrier protein. Proteins 86:664-675. Link

Wagner, D.T., Zhang, Z., Meoded, R.A., Cepeda, A.J., Piel, J., Keatinge-Clay, A.T. (2018). Structural and functional studies of a pyran synthase domain from a trans-acyltransferase assembly line. ACS Chem. Biol. 13:975-983. Link

2017

Wagner, D.T., Zeng, J., Bailey, C.B., Gay, D.C., Yuan, F., Manion, H.R., Keatinge-Clay, A.T. (2017). Structural and functional trends in dehydrating bimodules from trans-acyltransferase polyketide synthases. Structure 25:1045-1055. Link

Keatinge-Clay, A.T. (2017). Polyketide synthase modules redefined. Angew. Chem. Int. Ed. Engl. 56:4658-4660. Link

2016

Zeng, J., Wagner, D.T., Zhang, Z., Moretto, L., Addison, J.D., Keatinge-Clay, A.T. (2016). Portability and structure of the four-helix bundle docking domains of trans-acyltransferase modular polyketide synthases. ACS Chem. Biol. 11:2466-2474. Link

Wagner, D.T., Stevens, D.C., Mehaffey, R.M., Manion, H.R., Taylor, R.E., Brodbelt, J.S., Keatinge-Clay, A.T. (2016). alpha-Methylation follows condensation in the gephyronic acid modular polyketide synthase. Chem. Commun. 52:8822-8825. Link

Keatinge-Clay, A.T. (2016). The structural relationship between iterative and modular polyketide synthases. Cell Chem. Biol. 23:540-542. Link

Xie, X., Garg, A., Keatinge-Clay, A.T., Khosla, C., Cane, D.E. (2016). Epimerase and reductase activities of polyketide synthase ketoreductase domains utilize the same conserved tyrosine and serine residues. Biochemistry 55:1179-1186. Link

Gay, D.C., Wagner, D.T., Meinke, J.L., Zogzas, C.E., Gay, G.R., Keatinge-Clay, A.T. (2016). The LINKS motif zippers trans- acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex. J. Struct. Biol. 193:196-205. Link

Keatinge-Clay, A.T. (2016). Stereocontrol within polyketide assembly lines. Nat. Prod. Rep. 33:141-149. Link

2015

Bailey, C.B., Pasman, M.E., Keatinge-Clay, A.T. (2015). Substrate structure-activity relationships guide rational engineering of modular polyketide synthase ketoreductases. Chem. Comm. 52:792-795. Link

Fage, C.D., Meinke, J.L., Keatinge-Clay, A.T. (2015). Coenzyme A-free activity, crystal structure, and rational engineering of a promiscuous beta-ketoacyl thiolase from Ralstonia eutropha. J. Mol. Catal. B: Enzym. 121:113-121. Link

Mugnai, M.L., Shi, Y., Keatinge-Clay, A.T., Elber, R. (2015). Molecular dynamics studies of modular polyketide synthase ketoreductase stereospecificity. Biochemistry 54:2346-2359. Link

Fage, C.D., Isiorho, E.A., Liu, Y., Wagner, D.T., Liu, H.W., Keatinge-Clay, A.T. (2015). The structure of SpnF, a standalone enzyme that catalyzes [4 + 2] cycloaddition. Link Nat. Chem. Biol. 11:256-258.

Lee, J., Monzingo, A.F., Keatinge-Clay, A.T., Harshey, R.M. (2015). Structure of Salmonella FlhE, conserved member of a flagellar type III secretion operon. J. Mol. Biol. 427:1254-1262. Link

2014

Gay, D.C., Spear, P.J., Keatinge-Clay, A.T. (2014). A double-hotdog with a new trick: structure and mechanism of the trans-acyltransferase polyketide synthase enoyl-isomerase. ACS Chem. Biol. 9:2374-2381. Link

Garg, A., Xingiang, X., Keatinge-Clay, A.T., Khosla, C., Cane, D.E. (2014). Elucidation of the cryptic epimerase activity of redox-inactive ketoreductase domains from modular polyketide synthases by tandem equilibrium isotope exchange. J. Am. Chem. Soc. 136:10190-10193. Link

Gay, G., Wagner, D.T., Keatinge-Clay, A.T., Gay, D.C. (2014). Rapid modification of the pET-28 expression vector for ligation independent cloning using homologous recombination in Saccharomyces cerevisiae. Plasmid pii: S0147-619X(14)00075-4. Link

Fage, C.D., Henderson, J.C., Cannon, J.R., Brodbelt, J.S., Keatinge-Clay, A.T., Trent, M.S. (2014). Antimicrobial peptide resistance of Vibrio cholerae results from LPS modification pathway related to non-ribosomal peptide synthetases. ACS Chem. Biol. 9:2382-2392. Link

Isiorho, E.A., Jeon, B.-S., Liu, H.-w., Keatinge-Clay, A.T. (2014) Structural studies of the spinosyn forosaminyltransferase, SpnP. Biochemistry 53:4292-4301. Link

Fage, C.D., Brown, D.B., Boll, J.M., Keatinge-Clay, A.T., Trent, M.S. (2014). Crystallographic study of the EptC phosphoethanolamine transferase required for polymyxin resistance and motility in Campylobacter jejuni. Acta Cryst. D 70:2730-2739. Link

Brantley, J.N., Bailey, C.B., Cannon, J.R., Clark, K.A., Vanden Bout, D.A., Brodbelt, J.S., Keatinge-Clay, A.T., Bielawski, C.W. (2014). Mechanically modulating the photophysical properties of fluorescent protein biocomposites: new classes of ratio- and intensiometric sensors. Angew. Chem. 53:5088-5098. Link

Piasecki, S.K., Zheng, J., Axelrod, A.J., Detelich, M., Keatinge-Clay, A.T. (2014). Structural and functional studies of a trans-acyltransferase polyketide synthase ketoreductase the performs both alpha- and beta-ketoreduction. Proteins 82:2067-2077. Link

Gay, D.C., Gay, G., Axelrod, A.J., Jenner, M., Kohlhaas, C., Kampa, A., Oldham, N.J., Piel, J., Keatinge-Clay, A.T. (2014). A close look at a ketosynthase from a trans-acyltransferase modular polyketide synthase. Structure 22:444-451. Link

Hughes, A.J., Tibby, M.R., Wagner, D.T., Brantley, J.N., Keatinge-Clay, A.T. (2014). Investigating the reactivities of a polyketide synthase module through fluorescent click chemistry. Chem. Commun. 50: 5276-5278. Link

2013

Gay, D.C., You, Y.-O., Keatinge-Clay, A.T., Cane D.E. (2013). Structural and stereospecificity of the dehydratase domain from the terminal module of the rifamycin polyketide synthase. Biochemistry 52:8916-8928. Link

Enyeart, P.J., Chirieleison, S.M., Dao, M.N., Perutka, J., Quandt, E.M., Yao, J., Whitt, J.T., Keatinge-Clay, A.T., Lambowitz, A.M., Georgiou, G., Ellington, A.D. (2013). Generalized bacterial genome editing using mobile group II introns and Cre-lox. Mol. Syst. Biol. 9: 685-700. Link

Zheng, J., Piasecki, S.K., Keatinge-Clay, A.T. (2013). Structural studies of an A2-type modular polyketide synthase ketoreductase reveal features controlling alpha-substituent stereochemistry. ACS Chem. Biol. 8:1964-1971. Link

Zheng, J., Fage, C.D., Demeler, B., Hoffman, D.W., Keatinge-Clay, A.T. (2013). The missing linker: a dimerization motif located within polyketide synthase modules. ACS Chem. Biol. 8:1263-1270. Link

Brantley, J.N., Bailey, C.B., Wiggins, K.M., Keatinge-Clay, A.T., Bielawski, C.W. (2013). Mechanobiochemistry: harnessing biomacromolecules for force-responsive materials. Polym. Chem. 4:3916-3928. Link

2012

Harper, A.D., Bailey, C.B., Edwards, A.D., Detelich, J.F., Keatinge-Clay, A.T. (2012). Preparative, in vitro biocatalytic syntheses of triketide lactone building blocks. Chembiochem 13:2200-2203. Link

Keatinge-Clay, A.T. (2012). The structures of type I polyketide synthases. Nat. Prod. Rep. 29:1050-1073. Link

Piasecki, S.K. & Keatinge-Clay, A.T. (2012). Monitoring biocatalytic transformations mediated by polyketide synthase enzymes via fluorine NMR. Synlett 12:1840-1842. Link

Zheng, J., Gay, D.C., Demeler, B., White, M.A., Keatinge-Clay, A.T. (2012). Divergence of multimodular polyketide synthases revealed by a didomain structure. Nat. Chem. Biol. 8:615-621. Link

Hughes, A.J. & Keatinge-Clay, A.T. (2012). Employing a polyketide synthase module and thioesterase in the semipreparative biocatalysis of diverse triketide pyrones. Med. Chem. Commun. 3:956-959. Link

Isiorho, E., Liu, H.-w., Keatinge-Clay, A.T. (2012). Structural studies of the spinosyn rhamnosyltransferase, SpnG. Biochemistry 51:1213-1222. Link

2011

Piasecki, S.K., Taylor, C.A., Detelich, J.F., Liu, J., Zheng, J., Komsoukaniants, A., Siegel, D.R., Keatinge-Clay, A.T. (2011). Employing modular polyketide synthase ketoreductases as biocatalysts in the preparative chemoenzymatic syntheses of diketide chiral building blocks. Chem. Biol. 18:1331-1340. Link

Zheng, J. & Keatinge-Clay, A.T. (2011). Structural and functional analysis of C2-type ketoreductases from modular polyketide synthases. J. Mol. Biol. 410:105-117. Link

Hughes, A.J. & Keatinge-Clay, A.T. (2011). Enzymatic extender unit generation for in vitro polyketide synthase reactions: structural and functional showcasing of Streptomyces coelicolor MatB. Chem. Biol. 18:165-176. Link

2010

Valenzano, C.R., You, Y.O., Garg, A., Keatinge-Clay, A.T., Khosla, C., Cane, D.E. (2010). Stereospecificity of the dehydratase domain of the erythromycin polyketide synthase. J. Am. Chem. Soc. 130:11598-11599. Link

Zheng, J., Taylor, C.A., Piasecki, S.K., Keatinge-Clay, A.T. (2010). Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase. Structure 18:913-922. Link

2008

Keatinge-Clay, A.T. (2008). Crystal structure of the erythromycin polyketide synthase dehydratase. J. Mol. Biol. 384:941-953. Link

Castonguay, R., Valenzano, C.R., Chen, A.Y., Keatinge-Clay, A.T., Khosla, C., Cane, D.E. (2008). Stereospecificity of ketoreductase domains 1 and 2 of the tylactone modular polyketide synthase" J. Am. Chem. Soc. 130:11598-11599. Link

2007

Keatinge-Clay, A.T. (2007). A tylosin ketoreductase reveals how chirality is determined in polyketides. Chem. Biol. 14:898-908. Link

2006

Keatinge-Clay, A.T. & Stroud, R.M. (2006). The structure of a ketoreductase determines the organization of the beta-carbon processing enzymes of modular polyketide synthases. Structure 14:737-748. Link

2004

Keatinge-Clay, A.T., Maltby, D.A., Medzihradsky, K.F., Khosla, C., Stroud, R.M. (2004). An antibiotic factory caught in action. Nat. Struct. Mol. Biol. 11:888-893. Link

2003

Keatinge-Clay, A.T., Shelat, A.A., Savage, D.F., Tsai, S.C., Miercke, L.J., O'Connell, J.D., Khosla, C., Stroud, R.M. (2003). Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase. Structure 11:147-154. Link

2002

Pan, H., Tsai, S., Meadows, E.S., Miercke, L.J., Keatinge-Clay, A.T., O'Connell, J., Khosla, C., Stroud, R.M. (2002). Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway. Structure 10:1559-1568. Link

2001

Serber, Z., Keatinge-Clay, A.T., Ledwidge, R., Kelly, A.E., Miller, S.M., Dotsch, V. (2001). High-resolution macromolecular NMR spectroscopy inside living cells. J. Am. Chem. Soc. 123:2446-2447. Link

1998

Jacobsen, J.R., Keatinge-Clay, A.T., Cane, D.E., Khosla, C. (1998). Precursor-directed biosynthesis of 12-ethyl erythromycin. Bioorg. Med. Chem. 6:1171-1177. Link