REFERENCES
[1] Nivina, A., Yuet, K. P., Hsu, J., and Khosla, C. (2019) Evolution and Diversity of Assembly-Line Polyketide Synthases,Chem Rev 119 , 12524-12547.
[2] Keatinge-Clay, A. T. (2017) The Uncommon Enzymology of Cis-Acyltransferase Assembly Lines, Chem Rev 117 , 5334-5366.
[3] Helfrich, E. J. N., and Piel, J. (2016) Biosynthesis of polyketides by trans-AT polyketide synthases, Nat Prod Rep33 , 231-316.
[4] Keatinge-Clay, A. T. (2012) The structures of type I polyketide synthases, Nat Prod Rep 29 , 1050-1073.
[5] Kapur, S., Lowry, B., Yuzawa, S., Kenthirapalan, S., Chen, A. Y., Cane, D. E., and Khosla, C. (2012) Reprogramming a module of the 6-deoxyerythronolide B synthase for iterative chain elongation,Proc Natl Acad Sci U S A 109 , 4110-4115.
[6] Kapur, S., Chen, A. Y., Cane, D. E., and Khosla, C. (2010) Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase, Proc Natl Acad Sci U S A 107 , 22066-22071.
[7] Bagde, S. R., Mathews, II, Fromme, J. C., and Kim, C. Y. (2021) Modular polyketide synthase contains two reaction chambers that operate asynchronously, Science 374 , 723-729.
[8] Cogan, D. P., Zhang, K., Li, X., Li, S., Pintilie, G. D., Roh, S. H., Craik, C. S., Chiu, W., and Khosla, C. (2021) Mapping the catalytic conformations of an assembly-line polyketide synthase module,Science 374 , 729-734.
[9] Chisuga, T., Murakami, S., Miyanaga, A., Kudo, F., and Eguchi, T. (2023) Structure-Based Analysis of Transient Interactions between Ketosynthase-like Decarboxylase and Acyl Carrier Protein in a Loading Module of Modular Polyketide Synthase, ACS Chem Biol 18 , 1398-1404.
[10] Dutta, S., Whicher, J. R., Hansen, D. A., Hale, W. A., Chemler, J. A., Congdon, G. R., Narayan, A. R., Hakansson, K., Sherman, D. H., Smith, J. L., and Skiniotis, G. (2014) Structure of a modular polyketide synthase, Nature 510 , 512-517.
[11] Kim, S. K., Dickinson, M. S., Finer-Moore, J., Guan, Z., Kaake, R. M., Echeverria, I., Chen, J., Pulido, E. H., Sali, A., Krogan, N. J., Rosenberg, O. S., and Stroud, R. M. (2023) Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13, Nat Struct Mol Biol 30 , 296-308.
[12] Desta, I. T., Porter, K. A., Xia, B., Kozakov, D., and Vajda, S. (2020) Performance and Its Limits in Rigid Body Protein-Protein Docking, Structure 28 , 1071-1081 e1073.
[13] Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., Millan, C., Park, H., Adams, C., Glassman, C. R., DeGiovanni, A., Pereira, J. H., Rodrigues, A. V., van Dijk, A. A., Ebrecht, A. C., Opperman, D. J., Sagmeister, T., Buhlheller, C., Pavkov-Keller, T., Rathinaswamy, M. K., Dalwadi, U., Yip, C. K., Burke, J. E., Garcia, K. C., Grishin, N. V., Adams, P. D., Read, R. J., and Baker, D. (2021) Accurate prediction of protein structures and interactions using a three-track neural network, Science373 , 871-876.
[14] Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Zidek, A., Potapenko, A., Bridgland, A., Meyer, C., Kohl, S. A. A., Ballard, A. J., Cowie, A., Romera-Paredes, B., Nikolov, S., Jain, R., Adler, J., Back, T., Petersen, S., Reiman, D., Clancy, E., Zielinski, M., Steinegger, M., Pacholska, M., Berghammer, T., Bodenstein, S., Silver, D., Vinyals, O., Senior, A. W., Kavukcuoglu, K., Kohli, P., and Hassabis, D. (2021) Highly accurate protein structure prediction with AlphaFold,Nature 596 , 583-589.
[15] Evans, R., O’Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Žídek, A., Bates, R., Blackwell, S., Yim, J., Ronneberger, O., Bodenstein, S., Zielinski, M., Bridgland, A., Potapenko, A., Cowie, A., Tunyasuvunakool, K., Jain, R., Clancy, E., Kohli, P., Jumper, J., and Hassabis, D. (2021) Protein complex prediction with AlphaFold-Multimer, bioRxiv , 2021.2010.2004.463034.
[16] Zhang, L., Hashimoto, T., Qin, B., Hashimoto, J., Kozone, I., Kawahara, T., Okada, M., Awakawa, T., Ito, T., Asakawa, Y., Ueki, M., Takahashi, S., Osada, H., Wakimoto, T., Ikeda, H., Shin-Ya, K., and Abe, I. (2017) Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides, Angew Chem Int Ed Engl 56 , 1740-1745.
[17] Keatinge-Clay, A. T. (2017) Polyketide Synthase Modules Redefined, Angew Chem Int Ed Engl 56 , 4658-4660.
[18] Hirsch, M., Fitzgerald, B. J., and Keatinge-Clay, A. T. (2021) How cis-Acyltransferase Assembly-Line Ketosynthases Gatekeep for Processed Polyketide Intermediates, ACS Chem Biol 16 , 2515-2526.
[19] Vander Wood, D. A., and Keatinge-Clay, A. T. (2018) The modules of trans-acyltransferase assembly lines redefined with a central acyl carrier protein, Proteins 86 , 664-675.
[20] Hirsch, M., Kumru, K., Desai, R. R., Fitzgerald, B. J., Miyazawa, T., Ray, K. A., Saif, N., Spears, S., and Keatinge-Clay, A. T. (2021) Insights into modular polyketide synthase loops aided by repetitive sequences, Proteins 89 , 1099-1110.
[21] Chandran, S. S., Menzella, H. G., Carney, J. R., and Santi, D. V. (2006) Activating hybrid modular interfaces in synthetic polyketide synthases by cassette replacement of ketosynthase domains, Chem Biol 13 , 469-474.
[22] Peng, H., Ishida, K., Sugimoto, Y., Jenke-Kodama, H., and Hertweck, C. (2019) Emulating evolutionary processes to morph aureothin-type modular polyketide synthases and associated oxygenases,Nat Commun 10 , 3918.
[23] Miyazawa, T., Hirsch, M., Zhang, Z., and Keatinge-Clay, A. T. (2020) An in vitro platform for engineering and harnessing modular polyketide synthases, Nat Commun 11 , 80.
[24] Miyazawa, T., Fitzgerald, B. J., and Keatinge-Clay, A. T. (2021) Preparative production of an enantiomeric pair by engineered polyketide synthases, Chem Commun .
[25] Zhang, J., Bista, R., Miyazawa, T., and 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.
[26] Broadhurst, R. W., Nietlispach, D., Wheatcroft, M. P., Leadlay, P. F., and Weissman, K. J. (2003) The structure of docking domains in modular polyketide synthases, Chem Biol 10 , 723-731.
[27] Buchholz, T. J., Geders, T. W., Bartley, F. E., 3rd, Reynolds, K. A., Smith, J. L., and Sherman, D. H. (2009) Structural basis for binding specificity between subclasses of modular polyketide synthase docking domains, ACS Chem Biol 4 , 41-52.
[28] Holak, T. A., Nilges, M., Prestegard, J. H., Gronenborn, A. M., and Clore, G. M. (1988) Three-dimensional structure of acyl carrier protein in solution determined by nuclear magnetic resonance and the combined use of dynamical simulated annealing and distance geometry,Eur J Biochem 175 , 9-15.
[29] Tang, Y., Kim, C. Y., Mathews, II, Cane, D. E., and Khosla, C. (2006) The 2.7-Angstrom crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase, Proc Natl Acad Sci U S A 103 , 11124-11129.
[30] Tang, Y., Chen, A. Y., Kim, C. Y., Cane, D. E., and Khosla, C. (2007) Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase, Chem Biol14 , 931-943.
[31] Whicher, J. R., Smaga, S. S., Hansen, D. A., Brown, W. C., Gerwick, W. H., Sherman, D. H., and Smith, J. L. (2013) Cyanobacterial polyketide synthase docking domains: a tool for engineering natural product biosynthesis, Chem Biol 20 , 1340-1351.
[32] Guzman, K. M., Cogan, D. P., Brodsky, K. L., Soohoo, A. M., Li, X., Sevillano, N., Mathews, II, Nguyen, K. P., Craik, C. S., and Khosla, C. (2023) Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase, Biochemistry 62 , 1589-1593.
[33] Emsley, P., Lohkamp, B., Scott, W. G., and Cowtan, K. (2010) Features and development of Coot, Acta Crystallogr D Biol Crystallogr 66 , 486-501.
[34] Cunningham, B. C., and Wells, J. A. (1989) High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis, Science 244 , 1081-1085.
[35] Murli, S., Kennedy, J., Dayem, L. C., Carney, J. R., and Kealey, J. T. (2003) Metabolic engineering of Escherichia coli for improved 6-deoxyerythronolide B production, J Ind Microbiol Biotechnol 30 , 500-509.
[36] Sussmuth, R. D., and Mainz, A. (2017) Nonribosomal Peptide Synthesis-Principles and Prospects, Angew Chem Int Ed Engl56 , 3770-3821.
[37] Ray, K. A. S., N.; Keatinge-Clay, A.T. (2023) Modular polyketide synthase ketosynthases collaborate with upstream dehydratases to install double bonds, Under review at JACS .