Structural analysis of protein–protein interactions in type I polyketide synthases

References

• Aggarwal R, Caffrey P, Leadlay PF, et al. (1995). The thioesterase of the erythromycin-producing polyketide synthase – mechanistic studies invitro to investigate its mode of action and substrate-specificity. J Chem Soc, Chem Commun preprint1519–20
   Google Scholar
• Akey DL, Kittendorf JD, Giraldes JW, et al. (2006). Structural basis for macrolactonization by the pikromycin thioesterase. Nat Chem Biol 2:537–42
   Google Scholar
• Akey DL, Razelun JR, Tehranisa J, et al. (2010). Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway. Structure 18:94–105
   Google Scholar
• Alekseyev VY, Liu CW, Cane DE, et al. (2007). Solution structure and proposed domain domain recognition interface of an acyl carrier protein domain from a modular polyketide synthase. Protein Sci 16:2093–107
   PubMed Web of Science ®Google Scholar
• Ames BD, Nguyen C, Bruegger J, et al. (2012). Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis. Proc Nat Acad Sci USA 109:11144–9
   PubMed Web of Science ®Google Scholar
• Anand S, Mohanty D. (2012). Modeling holo-ACP:DH and holo-ACP:KR complexes of modular polyketide synthases: a docking and molecular dynamics study. BMC Struct Biol 12:10
   Google Scholar
• Asturias FJ, Chadick JZ, Cheung IK, et al. (2005). Structure and molecular organization of mammalian fatty acid synthase. Nat Struct Mol Biol 12:225–32
   PubMed Web of Science ®Google Scholar
• Auclair K, Sutherland A, Kennedy J, et al. (2000). Lovastatin nonaketide synthase catalyzes an intramolecular Diels–Alder reaction of a substrate analogue. J Am Chem Soc 122:11519–20
   Google Scholar
• Bedford D, Jacobsen JR, Luo G, et al. (1996). A functional chimeric modular polyketide synthase generated via domain replacement. Chem Biol 3:827–31
   PubMed Web of Science ®Google Scholar
• Brignole EJ, Smith S, Asturias FJ. (2009). Conformational flexibility of metazoan fatty acid synthase enables catalysis. Nat Struct Mol Biol 16:190–7
   PubMedGoogle Scholar
• Broadhurst RW, Nietlispach D, Wheatcroft MP, et al. (2003). The structure of docking domains in modular polyketide synthases. Chem Biol 10:723–31
   Google Scholar
• Busche AE, Aranko AS, Talebzadeh-Farooji M, et al. (2009). Segmental isotopic labeling of a central domain in a multidomain protein by protein trans-splicing using only one robust DnaE intein. Angew Chem Int Ed Engl 48:6128–31
   Google Scholar
• Busche AE, Gottstein D, Hein C, et al. (2012). Characterization of molecular interactions between ACP and halogenase domains in the curacin A polyketide synthase. ACS Chem Biol 7:378–86
   Google Scholar
• Cane DE. (2010). Programming of erythromycin biosynthesis by a modular polyketide synthase. J Biol Chem 285:27517–23
   PubMed Web of Science ®Google Scholar
• Cane DE, Walsh CT. (1999). The parallel and convergent universes of polyketide synthases and nonribosomal peptide synthetases. Chem Biol 6:R319–25
   PubMed Web of Science ®Google Scholar
• Cantu DC, Forrester MJ, Charov K, et al. (2012). Acyl carrier protein structural classification and normal mode analysis. Protein Sci 21:655–66
   Google Scholar
• Chakravarty B, Gu Z, Chirala SS, et al. (2004). Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain. Proc Nat Acad Sci USA 101:15567–72
   PubMed Web of Science ®Google Scholar
• Chan YA, Podevels AM, Kevany BM, et al. (2009). Biosynthesis of polyketide synthase extender units. Nat Prod Rep 26:90–114
   PubMed Web of Science ®Google Scholar
• Charkoudian LK, Liu CW, Capone S, et al. (2011). Probing the interactions of an acyl carrier protein domain from the 6-deoxyerythronolide B synthase. Protein Sci 20:1244–55
   Google Scholar
• Chen AY, Cane DE, Khosla C. (2007). Structure-based dissociation of a type I polyketide synthase module. Chem Biol 14:784–92
   Google Scholar
• Chen AY, Schnarr NA, Kim CY, et al. (2006). Extender unit and acyl carrier protein specificity of ketosynthase domains of the 6-deoxyerythronolide B synthase. J Am Chem Soc 128:3067–74
   Google Scholar
• Cheng YQ, Tang GL, Shen B. (2003). Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis. Proc Nat Acad Sci USA 100:3149–54
   PubMed Web of Science ®Google Scholar
• Claxton HB, Akey DL, Silver MK, et al. (2009). Structure and functional analysis of RifR, the type II thioesterase from the rifamycin biosynthetic pathway. J Biol Chem 284:5021–9
   Google Scholar
• Cox RJ. (2007). Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. Org Biomol Chem 5:2010–26
   Web of Science ®Google Scholar
• Crawford JM, Korman TP, Labonte JW, et al. (2009). Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. Nature 461:1139–43
   Google Scholar
• Crawford JM, Thomas PM, Scheerer JR, et al. (2008). Deconstruction of iterative multidomain polyketide synthase function. Science 320:243–6
   PubMed Web of Science ®Google Scholar
• Crump MP, Crosby J, Dempsey CE, et al. (1997). Solution structure of the actinorhodin polyketide synthase acyl carrier protein from Streptomyces coelicolor A3(2). Biochemistry 36:6000–8
   Google Scholar
• Dillon SC, Bateman A. (2004). The hotdog fold: wrapping up a superfamily of thioesterases and dehydratases. BMC Bioinform 5:109
   PubMed Web of Science ®Google Scholar
• Du L, Lou L. (2010). PKS and NRPS release mechanisms. Nat Prod Rep 27:255–78
   PubMed Web of Science ®Google Scholar
• Evans SE, Williams C, Arthur CJ, et al. (2008). An ACP structural switch: conformational differences between the apo and holo forms of the actinorhodin polyketide synthase acyl carrier protein. ChemBioChem 9:2424–32
   Google Scholar
• Evans SE, Williams C, Arthur CJ, et al. (2009). Probing the Interactions of early polyketide intermediates with the actinorhodin ACP from S. coelicolor A3(2). J Mol Biol 389:511–28
   Google Scholar
• Findlow SC, Winsor C, Simpson TJ, et al. (2003). Solution structure and dynamics of oxytetracycline polyketide synthase acyl carrier protein from Streptomyces rimosus. Biochemistry 42:8423–33
   Google Scholar
• Fischbach MA, Walsh CT. (2006). Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms. Chem Rev 106:3468–96
   PubMed Web of Science ®Google Scholar
• Frueh DP, Arthanari H, Koglin A, et al. (2008). Dynamic thiolation–thioesterase structure of a non-ribosomal peptide synthetase. Nature 454:903–6
   Google Scholar
• Fujii I, Watanabe A, Sankawa U, et al. (2001). Identification of Claisen cyclase domain in fungal polyketide synthase WA, a naphthopyrone synthase of Aspergillus nidulans. Chem Biol 8:189–97
   Google Scholar
• Gehret JJ, Gu L, Gerwick WH, et al. (2011). Terminal alkene formation by the thioesterase of curacin A biosynthesis: structure of a decarboxylating thioesterase. J Biol Chem 286:14445–54
   Google Scholar
• Giraldes JW, Akey DL, Kittendorf JD, et al. (2006). Structural and mechanistic insights into polyketide macrolactonization from polyketide-based affinity labels. Nat Chem Biol 2:531–6
   Google Scholar
• Gokhale RS, Tsuji SY, Cane DE, et al. (1999). Dissecting and exploiting intermodular communication in polyketide synthases. Science 284:482–5
   PubMed Web of Science ®Google Scholar
• Guo X, Liu T, Valenzano CR, et al. (2010). Mechanism and stereospecificity of a fully saturating polyketide synthase module: nanchangmycin synthase module 2 and its dehydratase domain. J Am Chem Soc 132:14694–6
   Google Scholar
• Haushalter RW, Filipp FV, Ko KS, et al. (2011). Binding and pK(a) modulation of a polycyclic substrate analogue in a type II polyketide acyl carrier protein. ACS Chem Biol 6:413–18
   Google Scholar
• Haushalter RW, Worthington AS, Hur GH, et al. (2008). An orthogonal purification strategy for isolating crosslinked domains of modular synthases. Bioorg Med Chem Lett 18:3039–42
   Google Scholar
• Haydock SF, Aparicio JF, Molnar I, et al. (1995). Divergent sequence motifs correlated with the substrate specificity of (methyl)malonyl-CoA:acyl carrier protein transacylase domains in modular polyketide synthases. FEBS Lett 374:246–8
   PubMed Web of Science ®Google Scholar
• Hertweck C. (2009). The biosynthetic logic of polyketide diversity. Angew Chem Int Ed Engl 48:4688–716
   PubMed Web of Science ®Google Scholar
• Jenke-Kodama H, Sandmann A, Muller R, et al. (2005). Evolutionary implications of bacterial polyketide synthases. Mol Biol Evol 22:2027–39
   PubMed Web of Science ®Google Scholar
• Joshi AK, Rangan VS, Smith S. (1998a). Differential affinity labeling of the two subunits of the homodimeric animal fatty acid synthase allows isolation of heterodimers consisting of subunits that have been independently modified. J Biol Chem 273:4937–43
   Google Scholar
• Joshi AK, Rangan VS, Witkowski A, et al. (2003). Engineering of an active animal fatty acid synthase dimer with only one competent subunit. Chem Biol 10:169–73
   Google Scholar
• Joshi AK, Witkowski A, Smith S. (1997). Mapping of functional interactions between domains of the animal fatty acid synthase by mutant complementation in vitro. Biochemistry 36:2316–22
   Google Scholar
• Joshi AK, Witkowski A, Smith S. (1998b). The malonyl/acetyltransferase and beta-ketoacyl synthase domains of the animal fatty acid synthase can cooperate with the acyl carrier protein domain of either subunit. Biochemistry 37:2515–23
   PubMedGoogle Scholar
• Kapur S, Chen AY, Cane DE, et al. (2010). Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase. Proc Nat Acad Sci USA 107:22066–71
   PubMedGoogle Scholar
• Kapur S, Lowry B, Yuzawa S, et al. (2012). Reprogramming a module of the 6-deoxyerythronolide B synthase for iterative chain elongation. Proc Nat Acad Sci USA 109:4110–5
   Google Scholar
• Kapur S, Worthington A, Tang Y, et al. (2008). Mechanism based protein crosslinking of domains from the 6-deoxyerythronolide B synthase. Bioorg Med Chem Lett 18:3034–8
   Google Scholar
• Kavanagh K, Jornvall H, Persson B, et al. (2008). The SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell Mol Life Sci 65:3895–906
   PubMed Web of Science ®Google Scholar
• Keatinge-Clay AT. (2007). A tylosin ketoreductase reveals how chirality is determined in polyketides. Chem Biol 14:898–908
   Google Scholar
• Keatinge-Clay AT. (2008). Crystal structure of the erythromycin polyketide synthase dehydratase. J Mol Biol 384:941–53
   Google Scholar
• Keatinge-Clay AT. (2012). The structures of type I polyketide synthases. Nat Prod Rep 29:1050–73
   PubMed Web of Science ®Google Scholar
• Keatinge-Clay AT, Maltby DA, Medzihradszky KF, et al. (2004). An antibiotic factory caught in action. Nat Struct Mol Biol 11:888–93
   Google Scholar
• Keatinge-Clay AT, Shelat AA, Savage DF, et al. (2003). Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase. Structure 11:147–54
   Google Scholar
• Keatinge-Clay AT, Stroud RM. (2006). The structure of a ketoreductase determines the organization of the beta-carbon processing enzymes of modular polyketide synthases. Structure 14:737–48
   PubMed Web of Science ®Google Scholar
• Kennedy J, Auclair K, Kendrew SG, et al. (1999). Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284:1368–72
   PubMed Web of Science ®Google Scholar
• Khare D, Wang B, Gu LC, et al. (2010). Conformational switch triggered by alpha-ketoglutarate in a halogenase of curacin A biosynthesis. Proc Nat Acad Sci USA 107:14099–104
   Google Scholar
• Khosla C. (2009). Structures and mechanisms of polyketide synthases. J Org Chem 74:6416–20
   Google Scholar
• Khosla C, Gokhale RS, Jacobsen JR, et al. (1999). Tolerance and specificity of polyketide synthases. Annu Rev Biochem 68:219–53
   PubMed Web of Science ®Google Scholar
• Khosla C, Tang Y, Chen AY, et al. (2007). Structure and mechanism of the 6-deoxyerythronolide B synthase. Annu Rev Biochem 76:195–221
   PubMed Web of Science ®Google Scholar
• Kimber MS, Martin F, Lu Y, et al. (2004). The structure of (3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Pseudomonas aeruginosa. J Biol Chem 279:52593–602
   PubMed Web of Science ®Google Scholar
• Koglin A, Lohr F, Bernhard F, et al. (2008). Structural basis for the selectivity of the external thioesterase of the surfactin synthetase. Nature 454:907–11
   Google Scholar
• Kopp M, Irschik H, Pradella S, et al. (2005). Production of the tubulin destabilizer disorazol in Sorangium cellulosum: biosynthetic machinery and regulatory genes. ChemBioChem 6:1277–86
   Google Scholar
• Korman TP, Crawford JM, Labonte JW, et al. (2010). Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis. Proc Nat Acad Sci USA 107:6246–51
   PubMed Web of Science ®Google Scholar
• Kotaka M, Kong R, Qureshi I, et al. (2009). Structure and catalytic mechanism of the thioesterase CalE7 in enediyne biosynthesis. J Biol Chem 284:15739–49
   Google Scholar
• Kroken S, Glass NL, Taylor JW, et al. (2003). Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proc Nat Acad Sci USA 100:15670–5
   PubMed Web of Science ®Google Scholar
• Kumar P, Koppisch AT, Cane DE, et al. (2003). Enhancing the modularity of the modular polyketide synthases: transacylation in modular polyketide synthases catalyzed by malonyl-CoA:ACP transacylase. J Am Chem Soc 125:14307–12
   Google Scholar
• Kwan DH, Leadlay PF. (2010). Mutagenesis of a modular polyketide synthase enoylreductase domain reveals insights into catalysis and stereospecificity. ACS Chem Biol 5:829–38
   Google Scholar
• Kwan DH, Sun Y, Schulz F, et al. (2008). Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases. Chem Biol 15:1231–40
   Google Scholar
• La Clair JJ, Foley TL, Schegg TR, et al. (2004). Manipulation of carrier proteins in antibiotic biosynthesis. Chem Biol 11:195–201
   PubMedGoogle Scholar
• Lambalot RH, Gehring AM, Flugel RS, et al. (1996). A new enzyme superfamily – the phosphopantetheinyl transferases. Chem Biol 3:923–36
   PubMedGoogle Scholar
• Lau J, Cane DE, Khosla C. (2000). Substrate specificity of the loading didomain of the erythromycin polyketide synthase. Biochemistry 39:10514–20
   Google Scholar
• Lau J, Fu H, Cane DE, et al. (1999). Dissecting the role of acyltransferase domains of modular polyketide synthases in the choice and stereochemical fate of extender units. Biochemistry 38:1643–51
   Google Scholar
• Leesong M, Henderson BS, Gillig JR, et al. (1996). Structure of a dehydratase-isomerase from the bacterial pathway for biosynthesis of unsaturated fatty acids: two catalytic activities in one active site. Structure 4:253–64
   PubMed Web of Science ®Google Scholar
• Li Q, Khosla C, Puglisi JD, et al. (2003). Solution structure and backbone dynamics of the holo form of the frenolicin acyl carrier protein. Biochemistry 42:4648–57
   Google Scholar
• Li Y, Xu W, Tang Y. (2010). Classification, prediction, and verification of the regioselectivity of fungal polyketide synthase product template domains. J Biol Chem 285:22762–71
   Google Scholar
• Liew CW, Nilsson M, Chen MW, et al. (2012). Crystal structure of the acyltransferase domain of the iterative polyketide synthase in enediyne biosynthesis. J Biol Chem 287:23203–15
   Google Scholar
• Liew CW, Sharff A, Kotaka M, et al. (2010). Induced-fit upon ligand binding revealed by crystal structures of the hot-dog fold thioesterase in dynemicin biosynthesis. J Mol Biol 404:291–306
   Google Scholar
• Lim J, Kong R, Murugan E, et al. (2011). Solution structures of the acyl carrier protein domain from the highly reducing type I iterative polyketide synthase CalE8. PLoS One 6:e20549
   Google Scholar
• Liou GF, Lau J, Cane DE, et al. (2003). Quantitative analysis of loading and extender acyltransferases of modular polyketide synthases. Biochemistry 42:200–7
   Google Scholar
• Liu Y, Zheng T, Bruner SD. (2011). Structural basis for phosphopantetheinyl carrier domain interactions in the terminal module of nonribosomal peptide synthetases. Chem Biol 18:1482–8
   Google Scholar
• Ma SM, Li JW, Choi JW, et al. (2009). Complete reconstitution of a highly reducing iterative polyketide synthase. Science 326:589–92
   Google Scholar
• Ma SM, Zhan J, Xie X, et al. (2008). Redirecting the cyclization steps of fungal polyketide synthase. J Am Chem Soc 130:38–9
   Google Scholar
• Maier T, Jenni S, Ban N. (2006). Architecture of mammalian fatty acid synthase at 4.5 A resolution. Science 311:1258–62
   PubMed Web of Science ®Google Scholar
• Maier T, Leibundgut M, Ban N. (2008). The crystal structure of a mammalian fatty acid synthase. Science 321:1315–22
   PubMed Web of Science ®Google Scholar
• McDaniel R, Thamchaipenet A, Gustafsson C, et al. (1999). Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel “unnatural” natural products. Proc Nat Acad Sci USA 96:1846–51
   PubMed Web of Science ®Google Scholar
• Meier JL, Burkart MD. (2009). The chemical biology of modular biosynthetic enzymes. Chem Soc Rev 38:2012–45
   PubMed Web of Science ®Google Scholar
• Meier JL, Haushalter RW, Burkart MD. (2010). A mechanism based protein crosslinker for acyl carrier protein dehydratases. Bioorg Med Chem Lett 20:4936–9
   Google Scholar
• Moche M, Schneider G, Edwards P, et al. (1999). Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase. J Biol Chem 274:6031–34
   PubMed Web of Science ®Google Scholar
• Newman DJ, Cragg GM. (2012). Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–35
   PubMed Web of Science ®Google Scholar
• Nguyen T, Ishida K, Jenke-Kodama H, et al. (2008). Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection. Nat Biotechnol 26:225–33
   Google Scholar
• Nordling E, Jornvall H, Persson B. (2002). Medium-chain dehydrogenases/reductases (MDR). Family characterizations including genome comparisons and active site modeling. Eur J Biochem 269:4267–76
   PubMedGoogle Scholar
• Olsen JG, Kadziola A, von Wettstein-Knowles P, et al. (2001). Structures of beta-ketoacyl-acyl carrier protein synthase I complexed with fatty acids elucidate its catalytic machinery. Structure 9:233–43
   PubMed Web of Science ®Google Scholar
• Piel J, Hui DQ, Fusetani N, et al. (2004). Targeting modular polyketide synthases with iteratively acting acyltransferases from metagenomes of uncultured bacterial consortia. Environ Microbiol 6:921–7
   Google Scholar
• Ploskon E, Arthur CJ, Evans SE, et al. (2008). A mammalian type I fatty acid synthase acyl carrier protein domain does not sequester acyl chains. J Biol Chem 283:518–28
   Google Scholar
• Price AC, Rock CO, White SW. (2003). The 1.3-Angstrom-resolution crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Streptococcus pneumoniae. J Bacteriol 185:4136–43
   Google Scholar
• Price AC, Zhang YM, Rock CO, et al. (2001). Structure of beta-ketoacyl-[acyl carrier protein] reductase from Escherichia coli: negative cooperativity and its structural basis. Biochemistry 40:12772–81
   Google Scholar
• Quadri LE, Weinreb PH, Lei M, et al. (1998). Characterization of Sfp, a Bacillus subtilis phosphopantetheinyl transferase for peptidyl carrier protein domains in peptide synthetases. Biochemistry 37:1585–95
   PubMedGoogle Scholar
• Rangan VS, Joshi AK, Smith S. (2001). Mapping the functional topology of the animal fatty acid synthase by mutant complementation in vitro. Biochemistry 40:10792–9
   Google Scholar
• Rangan VS, Smith S. (1997). Alteration of the substrate specificity of the malonyl-CoA/acetyl-CoA:acyl carrier protein S-acyltransferase domain of the multifunctional fatty acid synthase by mutation of a single arginine residue. J Biol Chem 272:11975–8
   Google Scholar
• Reed MAC, Schweizer M, Szafranska AE, et al. (2003). The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to type II ACPs. Org Biomol Chem 1:463–71
   Google Scholar
• Reeves CD, Murli S, Ashley GW, et al. (2001). Alteration of the substrate specificity of a modular polyketide synthase acyltransferase domain through site-specific mutations. Biochemistry 40:15464–70
   Google Scholar
• Roujeinikova A, Baldock C, Simon WJ, et al. (2002). X-ray crystallographic studies on butyryl-ACP reveal flexibility of the structure around a putative acyl chain binding site. Structure 10:825–35
   Google Scholar
• Ruch FE, Vagelos PR. (1973). The isolation and general properties of Escherichia coli malonyl coenzyme A-acyl carrier protein transacylase. J Biol Chem 248:8086–94
   PubMed Web of Science ®Google Scholar
• Scaglione JB, Akey DL, Sullivan R, et al. (2010). Biochemical and structural characterization of the tautomycetin thioesterase: analysis of a stereoselective polyketide hydrolase. Angew Chem Int Ed Engl 49:5726–30
   PubMed Web of Science ®Google Scholar
• Serre L, Verbree EC, Dauter Z, et al. (1995). The Escherichia coli malonyl-coa-acyl carrier protein transacylase at 1.5-angstrom resolution – crystal structure of a fatty acid synthase component. J Biol Chem 270:12961–4
   PubMed Web of Science ®Google Scholar
• Sharma AK, Sharma SK, Surolia A, et al. (2006). Solution structures of conformationally equilibrium forms of holo-acyl carrier protein (PfACP) from Plasmodium falciparum provides insight into the mechanism of activation of ACPs. Biochemistry 45:6904–16
   Google Scholar
• Sharma KK, Boddy CN. (2007). The thioesterase domain from the pimaricin and erythromycin biosynthetic pathways can catalyze hydrolysis of simple thioester substrates. Bioorg Med Chem Lett 17:3034–7
   Google Scholar
• Shen B. (2003). Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms. Curr Opin Chem Biol 7:285–95
   PubMed Web of Science ®Google Scholar
• Shimomura Y, Kakuta Y, Fukuyama K. (2003). Crystal structures of the quinone oxidoreductase from Thermus thermophilus HB8 and its complex with NADPH: implication for NADPH and substrate recognition. J Bacteriol 185:4211–18
   Google Scholar
• Siskos AP, Baerga-Ortiz A, Bali S, et al. (2005). Molecular basis of Celmer's rules: stereochemistry of catalysis by isolated ketoreductase domains from modular polyketide synthases. Chem Biol 12:1145–53
   Google Scholar
• Smith JL, Sherman DH. (2008). Biochemistry: an enzyme assembly line. Science 321:1304–5
   Google Scholar
• Smith S, Tsai SC. (2007). The type I fatty acid and polyketide synthases: a tale of two megasynthases. Nat Prod Rep 24:1041–72
   PubMed Web of Science ®Google Scholar
• Smith S, Witkowski A, Joshi AK. (2003). Structural and functional organization of the animal fatty acid synthase. Prog Lipid Res 42:289–317
   PubMed Web of Science ®Google Scholar
• Staunton J, Weissman KJ. (2001). Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416
   PubMed Web of Science ®Google Scholar
• Tang Y, Chen AY, Kim CY, et al. (2007). Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase. Chem Biol 14:931–43
   Google Scholar
• Tang Y, Kim CY, Mathews II, et al. (2006). The 2.7-angstrom crystal structure of a 194-kDa homodimeric fragment of the 6-deoxyerythronolide B synthase. Proc Nat Acad Sci USA 103:11124–9
   PubMed Web of Science ®Google Scholar
• Tang Y, Lee TS, Khosla C. (2004). Engineered biosynthesis of regioselectively modified aromatic polyketides using bimodular polyketide synthases. PLoS Biol 2:227–38
   Google Scholar
• Tang Y, Tsai SC, Khosla C. (2003). Polyketide chain length control by chain length factor. J Am Chem Soc 125:12708–9
   Google Scholar
• Tran L, Broadhurst RW, Tosin M, et al. (2010). Insights into protein–protein and enzyme-substrate interactions in modular polyketide synthases. Chem Biol 17:705–16
   Google Scholar
• Tran L, Tosin M, Spencer JB, et al. (2008). Covalent linkage mediates communication between ACP and TE domains in modular polyketide synthases. ChemBioChem 9:905–15
   Google Scholar
• Tsai SC, Ames BD. (2009). Structural enzymology of polyketide synthases. Methods Enzymol 459:17–47
   Google Scholar
• Tsai SC, Lu HX, Cane DE, et al. (2002). Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthases. Biochemistry 41:12598–606
   PubMed Web of Science ®Google Scholar
• Tsai SC, Miercke LJ, Krucinski J, et al. (2001). Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel. Proc Nat Acad Sci USA 98:14808–13
   PubMed Web of Science ®Google Scholar
• Tsuji SY, Cane DE, Khosla C. (2001). Selective protein–protein interactions direct channeling of intermediates between polyketide synthase modules. Biochemistry 40:2326–31
   Google Scholar
• Upadhyay SK, Misra A, Srivastava R, et al. (2009). Structural insights into the acyl intermediates of the Plasmodium falciparum fatty acid synthesis pathway: the mechanism of expansion of the acyl carrier protein core. J Biol Chem 284:22390–400
   Google Scholar
• Valenzano CR, Lawson RJ, Chen AY, et al. (2009). The biochemical basis for stereochemical control in polyketide biosynthesis. J Am Chem Soc 131:18501–11
   Google Scholar
• Valenzano CR, You YO, Garg A, et al. (2010). Stereospecificity of the dehydratase domain of the erythromycin polyketide synthase. J Am Chem Soc 132:14697–9
   Google Scholar
• Walsh CT. (2008). The chemical versatility of natural-product assembly lines. Acc Chem Res 41:4–10
   PubMedGoogle Scholar
• Wang M, Zhou H, Wirz M, et al. (2009). A thioesterase from an iterative fungal polyketide synthase shows macrocyclization and cross coupling activity and may play a role in controlling iterative cycling through product offloading. Biochemistry 48:6288–90
   Google Scholar
• Wang Y, Schwieters CD, Tjandra N. (2012). Parameterization of solvent–protein interaction and its use on NMR protein structure determination. J Magn Reson 221:76–84
   Google Scholar
• Watanabe K, Wang CC, Boddy CN, et al. (2003). Understanding substrate specificity of polyketide synthase modules by generating hybrid multimodular synthases. J Biol Chem 278:42020–6
   Google Scholar
• Wattana-amorn P, Williams C, Ploskon E, et al. (2010). Solution structure of an acyl carrier protein domain from a fungal type I polyketide synthase. Biochemistry 49:2186–93
   Google Scholar
• Weissman KJ. (2009). Introduction to polyketide biosynthesis. Complex enzymes in microbial natural product. Biosynthesis Part B: Polyketides Aminocoumarins Carbohydrates 459:3–16
   Google Scholar
• Weissman KJ, Hong H, Popovic B, et al. (2006). Evidence for a protein–protein interaction motif on an acyl carrier protein domain from a modular polyketide synthase. Chem Biol 13:625–36
   PubMedGoogle Scholar
• Weissman KJ, Muller R. (2008). Protein–protein interactions in multienzyme megasynthetases. ChemBioChem 9:826–48
   Google Scholar
• Weissman KJ, Smith CJ, Hanefeld U, et al. (1998). The thioesterase of the erythromycin-producing polyketide synthase: influence of acyl chain structure on the mode of release of substrate analogues from the acyl enzyme intermediates. Angew Chem Int Edn 37:1437–40
   Google Scholar
• Wilson MC, Moore BS. (2012). Beyond ethylmalonyl-CoA: the functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity. Nat Prod Rep 29:72–86
   Google Scholar
• Witkowski A, Ghosal A, Joshi AK, et al. (2004). Head-to-head coiled arrangement of the subunits of the animal fatty acid synthase. Chem Biol 11:1667–76
   PubMed Web of Science ®Google Scholar
• Witkowski A, Joshi A, Smith S. (1996). Fatty acid synthase: in vitro complementation of inactive mutants. Biochemistry 35:10569–75
   Google Scholar
• Witkowski A, Joshi AK, Rangan VS, et al. (1999). Dibromopropanone cross-linking of the phosphopantetheine and active-site cysteine thiols of the animal fatty acid synthase can occur both inter- and intrasubunit – reevaluation of the side-by-side, antiparallel subunit model. J Biol Chem 274:11557–63
   Google Scholar
• Wong FT, Chen AY, Cane DE, et al. (2010). Protein–protein recognition between acyltransferases and acyl carrier proteins in multimodular polyketide synthases. Biochemistry 49:95–102
   PubMedGoogle Scholar
• Wong FT, Jin X, Mathews II, et al. (2011). Structure and mechanism of the trans-acting acyltransferase from the disorazole synthase. Biochemistry 50:6539–48
   PubMed Web of Science ®Google Scholar
• Worthington AS, Burkart MD. (2006). One-pot chemo-enzymatic synthesis of reporter-modified proteins. Org Biomol Chem 4:44–6
   Google Scholar
• Worthington AS, Porter DF, Burkart MD. (2010). Mechanism-based crosslinking as a gauge for functional interaction of modular synthases. Org Biomol Chem 8:1769–72
   Google Scholar
• Worthington AS, Rivera H, Torpey JW, et al. (2006). Mechanism-based protein cross-linking probes to investigate carrier protein-mediated biosynthesis. ACS Chem Biol 1:687–91
   Google Scholar
• Wu N, Cane DE, Khosla C. (2002). Quantitative analysis of the relative contributions of donor acyl carrier proteins, acceptor ketosynthases, and linker regions to intermodular transfer of intermediates in hybrid polyketide synthases. Biochemistry 41:5056–66
   PubMedGoogle Scholar
• Wu N, Tsuji SY, Cane DE, et al. (2001). Assessing the balance between protein–protein interactions and enzyme–substrate interactions in the channeling of intermediates between polyketide synthase modules. J Am Chem Soc 123:6465–74
   Google Scholar
• Xie X, Meehan MJ, Xu W, et al. (2009). Acyltransferase mediated polyketide release from a fungal megasynthase. J Am Chem Soc 131:8388–9
   Google Scholar
• Yadav G, Gokhale RS, Mohanty D. (2003). Computational approach for prediction of domain organization and substrate specificity of modular polyketide synthases. J Mol Biol 328:335–63
   Google Scholar
• Yin YF, Gokhale R, Khosla C, et al. (2001). Erythromycin biosynthesis. The 4-pro-S hydride of NADPH is utilized for ketoreduction by both module 5 and module 6 of the 6-deoxyerythronolide B synthase. Bioorg Med Chem Lett 11:1477–9
   Google Scholar
• Zhang L, Liu W, Xiao J, et al. (2007). Malonyl-CoA: acyl carrier protein transacylase from Helicobacter pylori: crystal structure and its interaction with acyl carrier protein. Protein Sci 16:1184–92
   Google Scholar
• Zhang YM, Rao MS, Heath RJ, et al. (2001). Identification and analysis of the acyl carrier protein (ACP) docking site on beta-ketoacyl-ACP synthase III. J Biol Chem 276:8231–8
   PubMed Web of Science ®Google Scholar
• Zhang YM, Wu B, Zheng J, et al. (2003). Key residues responsible for acyl carrier protein and beta-ketoacyl-acyl carrier protein reductase (FabG) interaction. J Biol Chem 278:52935–43
   Google Scholar
• Zhao C, Coughlin JM, Ju J, et al. (2010). Oxazolomycin biosynthesis in Streptomyces albus JA3453 featuring an “acyltransferase-less” type I polyketide synthase that incorporates two distinct extender units. J Biol Chem 285:20097–108
   PubMed Web of Science ®Google Scholar
• Zheng J, Gay DC, Demeler B, et al. (2012). Divergence of multimodular polyketide synthases revealed by a didomain structure. Nat Chem Biol 8:615–21
   PubMed Web of Science ®Google Scholar
• Zheng J, Keatinge-Clay AT. (2011). Structural and functional analysis of C2-type ketoreductases from modular polyketide synthases. J Mol Biol 410:105–17
   Google Scholar
• Zheng J, Taylor CA, Piasecki SK, et al. (2010). Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase. Structure 18:913–22
   Google Scholar
• Zhou H, Gao ZZ, Qiao KJ, et al. (2012). A fungal ketoreductase domain that displays substrate-dependent stereospecificity. Nat Chem Biol 8:331–3
   PubMedGoogle Scholar
• Zhou H, Zhan J, Watanabe K, et al. (2008). A polyketide macrolactone synthase from the filamentous fungus Gibberella zeae. Proc Nat Acad Sci USA 105:6249–54
   Google Scholar
• Zhu X, Yu F, Li XC, et al. (2007). Production of dihydroisocoumarins in Fusarium verticillioides by swapping ketosynthase domain of the fungal iterative polyketide synthase Fum1p with that of lovastatin diketide synthase. J Am Chem Soc 129:36–7
   PubMed Web of Science ®Google Scholar
• Zornetzer GA, Fox BG, Markley JL. (2006). Solution structures of spinach acyl carrier protein with decanoate and stearate. Biochemistry 45:5217–27
   Google Scholar