PKS and NRPS release mechanisms.

This review covers the recent literature on the release mechanisms for polyketides and nonribosomal peptides produced by microorganisms. The emphasis is on the novel enzymology and mechanistic insights revealed by the biosynthetic studies of new natural products.

[1]  Tiangang Liu,et al.  Identification of NanE as the thioesterase for polyether chain release in nanchangmycin biosynthesis. , 2006, Chemistry & biology.

[2]  Ben Shen,et al.  Polyketide biosynthesis beyond the type I, II and III polyketide synthase paradigms. , 2003, Current opinion in chemical biology.

[3]  B. Wilkinson,et al.  Combinatorial biosynthesis of polyketides and nonribosomal peptides. , 2001, Current opinion in chemical biology.

[4]  Kenji Watanabe,et al.  A polyketide macrolactone synthase from the filamentous fungus Gibberella zeae , 2008, Proceedings of the National Academy of Sciences.

[5]  Janet L. Smith,et al.  Structure and Functional Analysis of RifR, the Type II Thioesterase from the Rifamycin Biosynthetic Pathway* , 2009, Journal of Biological Chemistry.

[6]  H. Blöcker,et al.  From genetic diversity to metabolic unity: studies on the biosynthesis of aurafurones and aurafuron-like structures in myxobacteria and streptomycetes. , 2007, Journal of molecular biology.

[7]  K. Zaleta-Rivera,et al.  Functional replacement of the ketosynthase domain of FUM1 for the biosynthesis of fumonisins, a group of fungal reduced polyketides , 2006, Journal of Industrial Microbiology and Biotechnology.

[8]  K. Zaleta-Rivera,et al.  Biosynthesis of sphinganine-analog mycotoxins , 2008, Journal of Industrial Microbiology & Biotechnology.

[9]  S. Lynch,et al.  Amphotericin Biosynthesis in Streptomyces nodosus , 2003 .

[10]  Yan Zhu,et al.  Nanostructural evolution of Zn by dry roller vibration milling at room temperature , 2006 .

[11]  L. Du,et al.  Determining the biosynthetic sequence in the early steps of the fumonisin pathway by use of three gene-disruption mutants of Fusarium verticillioides. , 2004, Journal of agricultural and food chemistry.

[12]  B. Shen,et al.  Rapid PCR amplification of minimal enediyne polyketide synthase cassettes leads to a predictive familial classification model , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Hoffmeister,et al.  Accurate prediction of the Aspergillus nidulans terrequinone gene cluster boundaries using the transcriptional regulator LaeA. , 2007, Fungal genetics and biology : FG & B.

[14]  Daren W Brown,et al.  Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic gene cluster in Gibberella moniliformis. , 2003, Fungal genetics and biology : FG & B.

[15]  Christopher T Walsh,et al.  Vancomycin assembly: nature's way. , 2003, Angewandte Chemie.

[16]  E. Schmidt,et al.  Equisetin biosynthesis in Fusarium heterosporum. , 2005, Chemical communications.

[17]  D. Ehmann,et al.  Lysine biosynthesis in Saccharomyces cerevisiae: mechanism of alpha-aminoadipate reductase (Lys2) involves posttranslational phosphopantetheinylation by Lys5. , 1999, Biochemistry.

[18]  L. Merson-Davies,et al.  Analysis of five tyiosin biosynthetic genes from the tyllBA region of the Streptomyces fradiae genome , 1994, Molecular microbiology.

[19]  P. Leadlay,et al.  A hybrid modular polyketide synthase obtained by domain swapping. , 1996, Chemistry & biology.

[20]  S. Lynch,et al.  Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes. , 2001, Chemistry & biology.

[21]  W. Wohlleben,et al.  Phosphinothricin Tripeptide Synthetases in Streptomyces viridochromogenes Tü494 , 2005, Antimicrobial Agents and Chemotherapy.

[22]  Hui Hong,et al.  Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp. DSM4137. , 2007, Chemistry & biology.

[23]  Christopher J. Schofield,et al.  The Mechanism of ACV Synthetase. , 1997, Chemical reviews.

[24]  M. Marahiel,et al.  A new enzyme superfamily - the phosphopantetheinyl transferases. , 1996, Chemistry & biology.

[25]  David H Sherman,et al.  Developing tools for engineering hybrid polyketide synthetic pathways. , 2006, Current opinion in biotechnology.

[26]  P. Leadlay,et al.  Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage. , 1995, Science.

[27]  C. Townsend,et al.  Production of octaketide polyenes by the calicheamicin polyketide synthase CalE8: implications for the biosynthesis of enediyne core structures. , 2009, Journal of the American Chemical Society.

[28]  B. Persson,et al.  Medium- and short-chain dehydrogenase/reductase gene and protein families , 2008, Cellular and Molecular Life Sciences.

[29]  B. Shen,et al.  A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis , 2009, Proceedings of the National Academy of Sciences.

[30]  Mohamed A. Marahiel,et al.  Chemoenzymatic and Template-Directed Synthesis of Bioactive Macrocyclic Peptides , 2006, Microbiology and Molecular Biology Reviews.

[31]  Mohamed A. Marahiel,et al.  Modular Peptide Synthetases Involved in Nonribosomal Peptide Synthesis. , 1997, Chemical reviews.

[32]  R. Muñoz,et al.  Molecular characterization of the safracin biosynthetic pathway from Pseudomonas fluorescens A2‐2: designing new cytotoxic compounds , 2005, Molecular microbiology.

[33]  J. Thorson,et al.  The Calicheamicin Gene Cluster and Its Iterative Type I Enediyne PKS , 2002, Science.

[34]  T. Ellingsen,et al.  Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathway. , 2000, Chemistry & biology.

[35]  R. Cox,et al.  Biosynthesis of the 2‐Pyridone Tenellin in the Insect Pathogenic Fungus Beauveria bassiana , 2007, Chembiochem : a European journal of chemical biology.

[36]  P. Leadlay,et al.  Knowledge-based design of bimodular and trimodular polyketide synthases based on domain and module swaps: a route to simple statin analogues. , 1999, Chemistry & biology.

[37]  Michael D. Burkart,et al.  Biomimetic synthesis and optimization of cyclic peptide antibiotics , 2002, Nature.

[38]  J B McAlpine,et al.  An erythromycin analog produced by reprogramming of polyketide synthesis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[39]  C. Walsh,et al.  Dynamic thiolation–thioesterase structure of a non-ribosomal peptide synthetase , 2008, Nature.

[40]  C. Walsh,et al.  Terrequinone A biosynthesis through L-tryptophan oxidation, dimerization and bisprenylation , 2007, Nature Chemical Biology.

[41]  N. Kelleher,et al.  Deconstruction of Iterative Multidomain Polyketide Synthase Function , 2008, Science.

[42]  M. Marahiel,et al.  Characterization of the surfactin synthetase C-terminal thioesterase domain as a cyclic depsipeptide synthase. , 2002, Biochemistry.

[43]  N. Bate,et al.  Impact of thioesterase activity on tylosin biosynthesis in Streptomyces fradiae. , 1999, Chemistry & biology.

[44]  J. Vederas,et al.  Complete Reconstitution of a Highly Reducing Iterative Polyketide Synthase , 2009, Science.

[45]  M. Marahiel,et al.  Structural basis for the cyclization of the lipopeptide antibiotic surfactin by the thioesterase domain SrfTE. , 2002, Structure.

[46]  C. Walsh,et al.  Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a reductase-like R* domain in cyclopiazonate synthetase that forms and releases cyclo-acetoacetyl-L-tryptophan. , 2009, Biochemistry.

[47]  P. Leadlay,et al.  Evidence for the role of the monB genes in polyether ring formation during monensin biosynthesis. , 2006, Chemistry & biology.

[48]  C. Walsh,et al.  Post-translational modification of polyketide and nonribosomal peptide synthases. , 1997, Current opinion in chemical biology.

[49]  Thanh Vu,et al.  Crystal structure and functional analysis of tetracenomycin ARO/CYC: Implications for cyclization specificity of aromatic polyketides , 2008, Proceedings of the National Academy of Sciences.

[50]  Wolfgang Kroutil,et al.  Evidence that a Novel Thioesterase is Responsible for Polyketide Chain Release during Biosynthesis of the Polyether Ionophore Monensin , 2006, Chembiochem : a European journal of chemical biology.

[51]  R. Müller Don't classify polyketide synthases. , 2004, Chemistry & biology.

[52]  M. Fischbach,et al.  Total biosynthesis: in vitro reconstitution of polyketide and nonribosomal peptide pathways. , 2008, Natural product reports.

[53]  Jason W. Labonte,et al.  Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization , 2009, Nature.

[54]  W. Gerwick,et al.  Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase. , 2004, Journal of the American Chemical Society.

[55]  R. Cox,et al.  Authentic Heterologous Expression of the Tenellin Iterative Polyketide Synthase Nonribosomal Peptide Synthetase Requires Coexpression with an Enoyl Reductase , 2008, Chembiochem : a European journal of chemical biology.

[56]  R. Proctor,et al.  A polyketide synthase gene required for biosynthesis of fumonisin mycotoxins in Gibberella fujikuroi mating population A. , 1999, Fungal genetics and biology : FG & B.

[57]  C. Walsh,et al.  Yersiniabactin synthetase: a four-protein assembly line producing the nonribosomal peptide/polyketide hybrid siderophore of Yersinia pestis. , 2002, Chemistry and Biology.

[58]  J R Jacobsen,et al.  A functional chimeric modular polyketide synthase generated via domain replacement. , 1996, Chemistry & biology.

[59]  B. Shen,et al.  Biosynthesis of hybrid peptide-polyketide natural products. , 2001, Current opinion in drug discovery & development.

[60]  M. Fischbach,et al.  Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms. , 2006, Chemical reviews.

[61]  C. Walsh,et al.  Type II Thioesterase Restores Activity of a NRPS Module Stalled with an Aminoacyl‐S‐enzyme that Cannot Be Elongated , 2004, Chembiochem : a European journal of chemical biology.

[62]  J. Staunton,et al.  Polyketide biosynthesis: a millennium review. , 2001, Natural product reports.

[63]  R. Schobert,et al.  Tetramic and tetronic acids: an update on new derivatives and biological aspects. , 2008, Bioorganic & medicinal chemistry.

[64]  C. Walsh,et al.  Reconstitution and characterization of the Escherichia coli enterobactin synthetase from EntB, EntE, and EntF. , 1998, Biochemistry.

[65]  M. Marahiel,et al.  The Linear Pentadecapeptide Gramicidin Is Assembled by Four Multimodular Nonribosomal Peptide Synthetases That Comprise 16 Modules with 56 Catalytic Domains* , 2004, Journal of Biological Chemistry.

[66]  R. Cox,et al.  Late stage oxidations during the biosynthesis of the 2-pyridone tenellin in the entomopathogenic fungus Beauveria bassiana. , 2008, Journal of the American Chemical Society.

[67]  H. Blöcker,et al.  Novel features in a combined polyketide synthase/non-ribosomal peptide synthetase: the myxalamid biosynthetic gene cluster of the myxobacterium Stigmatella aurantiaca Sga15. , 2001, Chemistry & biology.

[68]  C. Townsend,et al.  Enzymology and Molecular Biology of Aflatoxin Biosynthesis. , 1997, Chemical reviews.

[69]  C. Walsh,et al.  How Nature Morphs Peptide Scaffolds into Antibiotics , 2009, Chembiochem : a European journal of chemical biology.

[70]  P. Leadlay,et al.  An acyl-carrier-protein-thioesterase domain from the 6-deoxyerythronolide B synthase of Saccharopolyspora erythraea. High-level production, purification and characterisation in Escherichia coli. , 1991, European journal of biochemistry.

[71]  K. Zaleta-Rivera,et al.  A bidomain nonribosomal peptide synthetase encoded by FUM14 catalyzes the formation of tricarballylic esters in the biosynthesis of fumonisins. , 2006, Biochemistry.

[72]  C. Walsh,et al.  The parallel and convergent universes of polyketide synthases and nonribosomal peptide synthetases. , 1999, Chemistry & biology.

[73]  Xing-Cong Li,et al.  Production of dihydroisocoumarins in Fusarium verticillioides by swapping ketosynthase domain of the fungal iterative polyketide synthase Fum1p with that of lovastatin diketide synthase. , 2007, Journal of the American Chemical Society.

[74]  S. Donadio,et al.  Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea. , 1992, Gene.

[75]  L. Miercke,et al.  Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: Versatility from a unique substrate channel , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Jeong-Ah Seo,et al.  Characterization of four clustered and coregulated genes associated with fumonisin biosynthesis in Fusarium verticillioides. , 2001, Fungal genetics and biology : FG & B.

[77]  C. Townsend,et al.  Initial characterization of a type I fatty acid synthase and polyketide synthase multienzyme complex NorS in the biosynthesis of aflatoxin B(1). , 2002, Chemistry & biology.

[78]  R. Cox,et al.  Characterisation of 3-methylorcinaldehyde synthase (MOS) in Acremonium strictum: first observation of a reductive release mechanism during polyketide biosynthesis. , 2007, Chemical communications.

[79]  W. Kelly,et al.  Analysis of the Indanomycin Biosynthetic Gene Cluster from Streptomyces antibioticus NRRL 8167 , 2009, Chembiochem : a European journal of chemical biology.

[80]  P. Güntert,et al.  Structural basis for the selectivity of the external thioesterase of the surfactin synthetase , 2008, Nature.

[81]  Joseph P Noel,et al.  The chalcone synthase superfamily of type III polyketide synthases. , 2003, Natural product reports.

[82]  L. Du,et al.  A PLP-dependent polyketide chain releasing mechanism in the biosynthesis of mycotoxin fumonisins in Fusarium verticillioides. , 2009, Journal of the American Chemical Society.

[83]  B. Shen,et al.  The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway. , 2007, Biochemistry.

[84]  B. Shen,et al.  Biosynthesis of enediyne antitumor antibiotics. , 2008, Current topics in medicinal chemistry.

[85]  R McDaniel,et al.  Formation of functional heterologous complexes using subunits from the picromycin, erythromycin and oleandomycin polyketide synthases. , 2000, Chemistry & biology.

[86]  W. Wohlleben,et al.  Three Thioesterases Are Involved in the Biosynthesis of Phosphinothricin Tripeptide in Streptomyces viridochromogenes Tü494 , 2008, Antimicrobial Agents and Chemotherapy.

[87]  B. Shen,et al.  Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027. , 2008, Journal of the American Chemical Society.

[88]  Wang Jiansheng,et al.  Mycotoxin fumonisins: Health impacts and biosynthetic mechanism∗ , 2006 .

[89]  M. Marahiel,et al.  Chemoenzymatic approach to enantiopure streptogramin B variants: characterization of stereoselective pristinamycin I cyclase from Streptomyces pristinaespiralis. , 2005, Journal of the American Chemical Society.

[90]  Corinna Lange,et al.  Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. , 2007, Nature chemical biology.

[91]  M. Marahiel,et al.  Regeneration of misprimed nonribosomal peptide synthetases by type II thioesterases , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[92]  C. Walsh,et al.  GliP, a multimodular nonribosomal peptide synthetase in Aspergillus fumigatus, makes the diketopiperazine scaffold of gliotoxin. , 2006, Biochemistry.

[93]  J. Malkinson,et al.  Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies. , 2007, Natural product reports.

[94]  M. Marahiel,et al.  Design and application of multimodular peptide synthetases. , 1999, Current opinion in biotechnology.

[95]  M. Marahiel,et al.  TioS T‐TE – a prototypical thioesterase responsible for cyclodimerization of the quinoline‐ and quinoxaline‐type class of chromodepsipeptides , 2009, The FEBS journal.

[96]  C. Méndez,et al.  Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin. , 1999, Chemistry & biology.

[97]  Janet L. Smith,et al.  Structural and mechanistic insights into polyketide macrolactonization from polyketide-based affinity labels , 2006, Nature chemical biology.

[98]  C. Walsh,et al.  Harnessing the biosynthetic code: combinations, permutations, and mutations. , 1998, Science.

[99]  R. Stroud,et al.  Insights into channel architecture and substrate specificity from crystal structures of two macrocycle-forming thioesterases of modular polyketide synthases. , 2002, Biochemistry.

[100]  M. Marahiel,et al.  Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetases. , 2000, Structure.

[101]  R. Müller,et al.  Myxochelin biosynthesis: direct evidence for two- and four-electron reduction of a carrier protein-bound thioester. , 2008, Journal of the American Chemical Society.

[102]  W. Metcalf,et al.  Molecular Cloning, Sequence Analysis, and Heterologous Expression of the Phosphinothricin Tripeptide Biosynthetic Gene Cluster from Streptomyces viridochromogenes DSM 40736 , 2005, Antimicrobial Agents and Chemotherapy.

[103]  J. Rohr,et al.  Characterization of kinetics and products of the Baeyer-Villiger oxygenase MtmOIV, the key enzyme of the biosynthetic pathway toward the natural product anticancer drug mithramycin from Streptomyces argillaceus. , 2005, Journal of the American Chemical Society.

[104]  Kira J. Weissman,et al.  Combinatorial biosynthesis of reduced polyketides , 2005, Nature Reviews Microbiology.

[105]  B. Moore,et al.  Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[106]  C. Walsh,et al.  Epothilone C macrolactonization and hydrolysis are catalyzed by the isolated thioesterase domain of epothilone polyketide synthase. , 2003, Journal of the American Chemical Society.

[107]  B. Shen,et al.  Iterative type I polyketide synthases for enediyne core biosynthesis. , 2009, Methods in enzymology.

[108]  M. Marahiel,et al.  The Iterative Gramicidin S Thioesterase Catalyzes Peptide Ligation and Cyclization , 2007, Chemistry & Biology.

[109]  B. Shen,et al.  Regiospecific chlorination of (S)-beta-tyrosyl-S-carrier protein catalyzed by SgcC3 in the biosynthesis of the enediyne antitumor antibiotic C-1027. , 2007, Journal of the American Chemical Society.

[110]  Kap-Hoon Han,et al.  Two different polyketide synthase genes are required for synthesis of zearalenone in Gibberella zeae , 2005, Molecular microbiology.

[111]  C. Kao,et al.  Gain-of-Function Mutagenesis of a Modular Polyketide Synthase , 1997 .

[112]  C. Walsh,et al.  Chemoenzymatic route to macrocyclic hybrid peptide/polyketide-like molecules. , 2003, Journal of the American Chemical Society.

[113]  B. Shen,et al.  The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase. , 2000, Chemistry & biology.

[114]  Richard H Baltz,et al.  Molecular engineering approaches to peptide, polyketide and other antibiotics , 2006, Nature Biotechnology.

[115]  Camilla M. Kao,et al.  Manipulation of macrolide ring size by directed mutagenesis of a modular polyketide synthase , 1995 .

[116]  Wen Liu,et al.  Characterization of the Saframycin A Gene Cluster from Streptomyces lavendulae NRRL 11002 Revealing a Nonribosomal Peptide Synthetase System for Assembling the Unusual Tetrapeptidyl Skeleton in an Iterative Manner , 2007, Journal of bacteriology.

[117]  E. Schmidt,et al.  Thioesterase-like role for fungal PKS-NRPS hybrid reductive domains. , 2008, Journal of the American Chemical Society.

[118]  M. Marahiel,et al.  The thioesterase domain of the fengycin biosynthesis cluster: a structural base for the macrocyclization of a non-ribosomal lipopeptide. , 2006, Journal of molecular biology.

[119]  Christopher T Walsh,et al.  Polyketide and Nonribosomal Peptide Antibiotics: Modularity and Versatility , 2004, Science.

[120]  C. Walsh,et al.  The lyngbyatoxin biosynthetic assembly line: chain release by four-electron reduction of a dipeptidyl thioester to the corresponding alcohol. , 2007, Journal of the American Chemical Society.

[121]  R. Müller,et al.  In vitro reconstitution of the myxochelin biosynthetic machinery of Stigmatella aurantiaca Sg a15: Biochemical characterization of a reductive release mechanism from nonribosomal peptide synthetases , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[122]  Wen Liu,et al.  Biosynthesis of 3-hydroxy-5-methyl-o-methyltyrosine in the saframycin/ safracin biosynthetic pathway. , 2009, Journal of microbiology and biotechnology.

[123]  T. C. Nesbitt,et al.  Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[124]  M. Marahiel,et al.  Loading peptidyl-coenzyme A onto peptidyl carrier proteins: a novel approach in characterizing macrocyclization by thioesterase domains. , 2003, Journal of the American Chemical Society.

[125]  M. Marahiel,et al.  Peptidyl thiophenols as substrates for nonribosomal peptide cyclases. , 2004, Angewandte Chemie.

[126]  J. Lescar,et al.  Structure and Catalytic Mechanism of the Thioesterase CalE7 in Enediyne Biosynthesis* , 2009, The Journal of Biological Chemistry.

[127]  B. Shen,et al.  Biosynthesis of the β-Amino Acid Moiety of the Enediyne Antitumor Antibiotic C-1027 Featuring β-Amino Acyl-S-carrier Protein Intermediates , 2005 .

[128]  J B McAlpine,et al.  Modular organization of genes required for complex polyketide biosynthesis. , 1991, Science.

[129]  P. Leadlay,et al.  Role of type II thioesterases: evidence for removal of short acyl chains produced by aberrant decarboxylation of chain extender units. , 2001, Chemistry & biology.

[130]  P. Dorrestein,et al.  Acyltransferase mediated polyketide release from a fungal megasynthase. , 2009, Journal of the American Chemical Society.

[131]  P. Leadlay,et al.  An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea , 1990, Nature.

[132]  M. Marahiel,et al.  Chemo- and regioselective peptide cyclization triggered by the N-terminal fatty acid chain length: the recombinant cyclase of the calcium-dependent antibiotic from Streptomyces coelicolor. , 2004, Biochemistry.

[133]  H. Blöcker,et al.  Unusual chemistry in the biosynthesis of the antibiotic chondrochlorens. , 2009, Chemistry & biology.

[134]  J. Rohr,et al.  Crystal structure of Baeyer-Villiger monooxygenase MtmOIV, the key enzyme of the mithramycin biosynthetic pathway . , 2009, Biochemistry.

[135]  R. Cox,et al.  Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. , 2007, Organic & biomolecular chemistry.

[136]  K. Zaleta-Rivera,et al.  Structure and Biosynthesis of Heat-Stable Antifungal Factor (HSAF), a Broad-Spectrum Antimycotic with a Novel Mode of Action , 2006, Antimicrobial Agents and Chemotherapy.

[137]  Nancy P Keller,et al.  Genomic mining for Aspergillus natural products. , 2006, Chemistry & biology.

[138]  B. Shen Biosynthesis of Aromatic Polyketides , 2000 .

[139]  A. Pospiech,et al.  A new Myxococcus xanthus gene cluster for the biosynthesis of the antibiotic saframycin Mx1 encoding a peptide synthetase. , 1995, Microbiology.

[140]  L. Du,et al.  Developing a genetic system for functional manipulations of FUM1, a polyketide synthase gene for the biosynthesis of fumonisins in Fusarium verticillioides. , 2005, FEMS microbiology letters.

[141]  M. Marahiel,et al.  Synthesis of linear gramicidin requires the cooperation of two independent reductases. , 2005, Biochemistry.

[142]  S. Horinouchi,et al.  Physically discrete beta-lactamase-type thioesterase catalyzes product release in atrochrysone synthesis by iterative type I polyketide synthase. , 2009, Chemistry & biology.

[143]  Ioanna Ntai,et al.  Benzodiazepine biosynthesis in Streptomyces refuineus. , 2007, Chemistry & biology.

[144]  B. Shen,et al.  Hybrid peptide-polyketide natural products: biosynthesis and prospects toward engineering novel molecules. , 2001, Metabolic engineering.

[145]  Tiangang Liu,et al.  Mechanism of thioesterase-catalyzed chain release in the biosynthesis of the polyether antibiotic nanchangmycin. , 2008, Chemistry & biology.

[146]  Zhao-Xun Liang,et al.  Characterization of a carbonyl-conjugated polyene precursor in 10-membered enediyne biosynthesis. , 2008, Journal of the American Chemical Society.

[147]  A. Watanabe,et al.  Identification of Claisen cyclase domain in fungal polyketide synthase WA, a naphthopyrone synthase of Aspergillus nidulans. , 2001, Chemistry & biology.

[148]  D. A. Thayer,et al.  Macrolactamization of glycosylated peptide thioesters by the thioesterase domain of tyrocidine synthetase. , 2004, Chemistry & biology.

[149]  B. Shen,et al.  A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis , 2008, Proceedings of the National Academy of Sciences.

[150]  Michael Müller,et al.  Biosynthetic Gene Cluster for the Polyenoyltetramic Acid α-Lipomycin , 2006, Antimicrobial Agents and Chemotherapy.

[151]  Janet L. Smith,et al.  Structural basis for macrolactonization by the pikromycin thioesterase , 2006, Nature chemical biology.

[152]  Yi Tang,et al.  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. , 2009, Biochemistry.

[153]  Wen Liu,et al.  Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 , 2002, Science.

[154]  C. Walsh,et al.  The thioesterase domain from a nonribosomal peptide synthetase as a cyclization catalyst for integrin binding peptides , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[155]  Z. Deng,et al.  The enzymology of polyether biosynthesis. , 2009, Methods in enzymology.

[156]  K. Zaleta-Rivera,et al.  An antibiotic complex from Lysobacter enzymogenes strain C3: antimicrobial activity and role in plant disease control. , 2008, Phytopathology.

[157]  J. Vederas,et al.  Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. , 1999, Science.

[158]  L. Du,et al.  Distinct ceramide synthases regulate polarized growth in the filamentous fungus Aspergillus nidulans. , 2005, Molecular biology of the cell.

[159]  D. Hopwood,et al.  Genetic Contributions to Understanding Polyketide Synthases. , 1997, Chemical reviews.

[160]  J. H. Yu,et al.  Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel type I polyketide synthase , 1995, Journal of bacteriology.