2024

Miyazawa, T., Keatinge-Clay, A.T. (2024). Refactoring the pikromycin synthase for the modular biosynthesis of macrolide antibiotics in E. coli. Nat. Chem., submitted.

Ray, K.A., Lin, S.N., Keatinge-Clay, A.T. (2024). Distinct acyl carrier protein docking sites help mediate the opposite stereoselectivities of A- and B-type modular polyketide synthase ketoreductases. Biochemistry, in review.

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