Genomic basis for natural product biosynthetic diversity in the actinomycetes.

The phylum Actinobacteria hosts diverse high G + C, Gram-positive bacteria that have evolved a complex chemical language of natural product chemistry to help navigate their fascinatingly varied lifestyles. To date, 71 Actinobacteria genomes have been completed and annotated, with the vast majority representing the Actinomycetales, which are the source of numerous antibiotics and other drugs from genera such as Streptomyces, Saccharopolyspora and Salinispora. These genomic analyses have illuminated the secondary metabolic proficiency of these microbes – underappreciated for years based on conventional isolation programs – and have helped set the foundation for a new natural product discovery paradigm based on genome mining. Trends in the secondary metabolomes of natural product-rich actinomycetes are highlighted in this review article, which contains 199 references.

[1]  E. Graziani,et al.  Recent Advances in the Chemistry, Biosynthesis and Pharmacology of Rapamycin Analogues , 2009 .

[2]  B. Moore,et al.  Biosynthesis of salinosporamides from alpha,beta-unsaturated fatty acids: implications for extending polyketide synthase diversity. , 2009, Journal of the American Chemical Society.

[3]  Anna Lechner,et al.  Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-l-methionine , 2009, Proceedings of the National Academy of Sciences.

[4]  M. Komatsu,et al.  Genome mining in Streptomyces avermitilis: A biochemical Baeyer-Villiger reaction and discovery of a new branch of the pentalenolactone family tree. , 2009, Biochemistry.

[5]  S. Horinouchi,et al.  DNA microarray analysis of global gene regulation by A-factor in Streptomyces griseus. , 2009, Microbiology.

[6]  Elke Dittmann,et al.  Bioinformatic perspectives on NRPS/PKS megasynthases: advances and challenges. , 2009, Natural product reports.

[7]  Peter Man-Un Ung,et al.  Automated genome mining for natural products , 2009, BMC Bioinformatics.

[8]  C. Khosla,et al.  Biosynthesis of aromatic polyketides in bacteria. , 2009, Accounts of chemical research.

[9]  D. Cane,et al.  Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor. Mechanism and stereochemistry of the enzymatic formation of epi-isozizaene. , 2009, Journal of the American Chemical Society.

[10]  C. Hertweck,et al.  Triggering cryptic natural product biosynthesis in microorganisms. , 2009, Organic & biomolecular chemistry.

[11]  Bradley S. Moore,et al.  Exploration and engineering of biosynthetic pathways in the marine actinomycete Salinispora tropica , 2009 .

[12]  N. Bruce,et al.  Insights into Sequence–Activity Relationships amongst Baeyer–Villiger Monooxygenases as Revealed by the Intragenomic Complement of Enzymes from Rhodococcus jostii RHA1 , 2009, ChemBioChem.

[13]  S. Lautru,et al.  An iterative nonribosomal peptide synthetase assembles the pyrrole-amide antibiotic congocidine in Streptomyces ambofaciens. , 2009, Chemistry & biology.

[14]  E. Graziani,et al.  Recent advances in the chemistry, biosynthesis and pharmacology of rapamycin analogs. , 2009, Natural product reports.

[15]  Carlos Olano,et al.  Antitumor compounds from actinomycetes: from gene clusters to new derivatives by combinatorial biosynthesis. , 2009, Natural product reports.

[16]  Philippe Horvath,et al.  Comparison of the Complete Genome Sequences of Bifidobacterium animalis subsp. lactis DSM 10140 and Bl-04 , 2009, Journal of bacteriology.

[17]  H. Naegeli,et al.  Ribosomally synthesized thiopeptide antibiotics targeting elongation factor Tu. , 2009, Journal of the American Chemical Society.

[18]  Gitanjali Yadav,et al.  Towards Prediction of Metabolic Products of Polyketide Synthases: An In Silico Analysis , 2009, PLoS Comput. Biol..

[19]  Alla Lapidus,et al.  Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria , 2009, The ISME Journal.

[20]  I. Hoof,et al.  CLUSEAN: a computer-based framework for the automated analysis of bacterial secondary metabolite biosynthetic gene clusters. , 2009, Journal of biotechnology.

[21]  W. Kelly,et al.  Thiostrepton biosynthesis: prototype for a new family of bacteriocins. , 2009, Journal of the American Chemical Society.

[22]  G. Challis,et al.  Strategies for the Discovery of New Natural Products by Genome Mining , 2009, Chembiochem : a European journal of chemical biology.

[23]  Harald Gross,et al.  Genomic mining--a concept for the discovery of new bioactive natural products. , 2009, Current opinion in drug discovery & development.

[24]  B. Shen,et al.  Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. , 2009, Chemistry & biology.

[25]  M. Fischbach,et al.  Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin , 2009, Proceedings of the National Academy of Sciences.

[26]  Andreas Wietzorrek,et al.  Extracellular signalling, translational control, two repressors and an activator all contribute to the regulation of methylenomycin production in Streptomyces coelicolor , 2009, Molecular microbiology.

[27]  P. Flatt,et al.  Biosynthetic Gene Cluster of Cetoniacytone A, an Unusual Aminocyclitol from the Endosymbiotic Bacterium Actinomyces sp. Lu 9419 , 2009, Chembiochem : a European journal of chemical biology.

[28]  B. Moore.  Extending the biosynthetic repertoire in ribosomal peptide assembly. , 2008, Angewandte Chemie.

[29]  G. Challis,et al.  2-Alkyl-4-hydroxymethylfuran-3-carboxylic acids, antibiotic production inducers discovered by Streptomyces coelicolor genome mining , 2008, Proceedings of the National Academy of Sciences.

[30]  J. Zucko,et al.  ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures , 2008, Nucleic acids research.

[31]  E. Bremer,et al.  Synthesis and Uptake of the Compatible Solutes Ectoine and 5-Hydroxyectoine by Streptomyces coelicolor A3(2) in Response to Salt and Heat Stresses , 2008, Applied and Environmental Microbiology.

[32]  S. Bruner,et al.  Structure elucidation and biosynthesis of fuscachelins, peptide siderophores from the moderate thermophile Thermobifida fusca , 2008, Proceedings of the National Academy of Sciences.

[33]  Christian Stolte,et al.  TB database: an integrated platform for tuberculosis research , 2008, Nucleic Acids Res..

[34]  R. H. Baltz.  Renaissance in antibacterial discovery from actinomycetes. , 2008, Current opinion in pharmacology.

[35]  C. Farnet,et al.  Biosynthesis of diazepinomicin/ECO-4601, a Micromonospora secondary metabolite with a novel ring system. , 2008, Journal of natural products.

[36]  Benjamin T. Circello,et al.  Biosynthesis of 2-Hydroxyethylphosphonate, an Unexpected Intermediate Common to Multiple Phosphonate Biosynthetic Pathways* , 2008, Journal of Biological Chemistry.

[37]  Alok Bhattacharya,et al.  MGDD: Mycobacterium tuberculosis Genome Divergence Database , 2008, BMC Genomics.

[38]  D. Cane,et al.  Biochemistry and molecular genetics of the biosynthesis of the earthy odorant methylisoborneol in Streptomyces coelicolor. , 2008, Journal of the American Chemical Society.

[39]  Gregory L Challis,et al.  Mining microbial genomes for new natural products and biosynthetic pathways. , 2008, Microbiology.

[40]  B. Moore,et al.  Engineered biosynthesis of antiprotealide and other unnatural salinosporamide proteasome inhibitors. , 2008, Journal of the American Chemical Society.

[41]  M. Komatsu,et al.  Identification and functional analysis of genes controlling biosynthesis of 2-methylisoborneol , 2008, Proceedings of the National Academy of Sciences.

[42]  S. Horinouchi,et al.  Phenolic Lipids Synthesized by Type III Polyketide Synthase Confer Penicillin Resistance on Streptomyces griseus* , 2008, Journal of Biological Chemistry.

[43]  Bradley S Moore,et al.  Mutasynthesis of fluorosalinosporamide, a potent and reversible inhibitor of the proteasome. , 2008, Angewandte Chemie.

[44]  P. Caffrey,et al.  Biosynthetic engineering of polyene macrolides towards generation of improved antifungal and antiparasitic agents. , 2008, Current topics in medicinal chemistry.

[45]  M. Sekine,et al.  Complete Genome Sequence of the Soil Actinomycete Kocuria rhizophila , 2008, Journal of bacteriology.

[46]  G. Challis.  Genome mining for novel natural product discovery. , 2008, Journal of medicinal chemistry.

[47]  S. Kelly,et al.  Biosynthesis of the Sesquiterpene Antibiotic Albaflavenone in Streptomyces coelicolor A3(2)* , 2008, Journal of Biological Chemistry.

[48]  Jun Ishikawa,et al.  Genome Sequence of the Streptomycin-Producing Microorganism Streptomyces griseus IFO 13350 , 2008, Journal of bacteriology.

[49]  Christopher T. Walsh,et al.  The evolution of gene collectives: How natural selection drives chemical innovation , 2008, Proceedings of the National Academy of Sciences.

[50]  William Fenical,et al.  Biosynthesis and structures of cyclomarins and cyclomarazines, prenylated cyclic peptides of marine actinobacterial origin. , 2008, Journal of the American Chemical Society.

[51]  N. Rouhier,et al.  Regulation of the Synthesis of the Angucyclinone Antibiotic Alpomycin in Streptomyces ambofaciens by the Autoregulator Receptor AlpZ and Its Specific Ligand , 2008, Journal of bacteriology.

[52]  L. Tisa,et al.  The implication of life style on codon usage patterns and predicted highly expressed genes for three Frankia genomes , 2008, Antonie van Leeuwenhoek.

[53]  S. Ōmura.  Ivermectin: 25 years and still going strong. , 2008, International journal of antimicrobial agents.

[54]  B. Moore,et al.  Unraveling the biosynthesis of the sporolide cyclohexenone building block. , 2008, Journal of the American Chemical Society.

[55]  Roberta Bordoni,et al.  Complete gene expression profiling of Saccharopolyspora erythraea using GeneChip DNA microarrays , 2007, Microbial cell factories.

[56]  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.

[57]  Nadia Kadi,et al.  A new family of ATP-dependent oligomerization-macrocyclization biocatalysts. , 2007, Nature chemical biology.

[58]  Margherita Sosio,et al.  Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics. , 2007, Natural product reports.

[59]  D. Cane,et al.  Biosynthesis of the earthy odorant geosmin by a bifunctional Streptomyces coelicolor enzyme. , 2007, Nature chemical biology.

[60]  M. Gelfand,et al.  Low‐molecular‐weight post‐translationally modified microcins , 2007, Molecular microbiology.

[61]  A. Tauch,et al.  Genomics of Actinobacteria: Tracing the Evolutionary History of an Ancient Phylum , 2007, Microbiology and Molecular Biology Reviews.

[62]  Jason Micklefield,et al.  Mining and engineering natural-product biosynthetic pathways. , 2007, Nature chemical biology.

[63]  C. Médigue,et al.  Exploring the genomes of Frankia , 2007 .

[64]  William Fenical,et al.  Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica , 2007, Proceedings of the National Academy of Sciences.

[65]  P. Dorrestein,et al.  Molecular Basis for Chloronium-mediated Meroterpene Cyclization , 2007, Journal of Biological Chemistry.

[66]  D. Mohanty,et al.  Versatile polyketide enzymatic machinery for the biosynthesis of complex mycobacterial lipids. , 2007, Natural product reports.

[67]  C. Perrin,et al.  Nucleophilic addition to a p-benzyne derived from an enediyne: a new mechanism for halide incorporation into biomolecules. , 2007, Journal of the American Chemical Society.

[68]  Markiyan Samborskyy,et al.  Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338 , 2007, Nature Biotechnology.

[69]  H. Ikeda,et al.  Pentalenolactone biosynthesis: Molecular cloning and assignment of biochemical function to PtlF, a short-chain dehydrogenase from Streptomyces avermitilis, and identification of a new biosynthetic intermediate. , 2007, Archives of biochemistry and biophysics.

[70]  S. Horinouchi,et al.  A-Factor and Phosphate Depletion Signals Are Transmitted to the Grixazone Biosynthesis Genes via the Pathway-Specific Transcriptional Activator GriR , 2007, Journal of bacteriology.

[71]  A. Saghatelian,et al.  A streamlined metabolic pathway for the biosynthesis of moenomycin A. , 2007, Chemistry & biology.

[72]  G. Challis,et al.  Non-linear enzymatic logic in natural product modular mega-synthases and -synthetases. , 2007, Current opinion in drug discovery & development.

[73]  S. Horinouchi,et al.  Biosynthesis of γ-butyrolactone autoregulators that switch on secondary metabolism and morphological development in Streptomyces , 2007, Proceedings of the National Academy of Sciences.

[74]  Eriko Takano,et al.  A cryptic type I polyketide synthase (cpk) gene cluster in Streptomyces coelicolor A3(2) , 2007, Archives of Microbiology.

[75]  William Fenical,et al.  Species-Specific Secondary Metabolite Production in Marine Actinomycetes of the Genus Salinispora , 2006, Applied and Environmental Microbiology.

[76]  Eugene Goltsman,et al.  Genome characteristics of facultatively symbiotic Frankia sp. strains reflect host range and host plant biogeography. , 2006, Genome research.

[77]  Paul R Jensen,et al.  Developing a new resource for drug discovery: marine actinomycete bacteria , 2006, Nature chemical biology.

[78]  Finian J. Leeper,et al.  The biosynthesis and regulation of bacterial prodiginines , 2006, Nature Reviews Microbiology.

[79]  V. Barbe,et al.  Evolution of the terminal regions of the Streptomyces linear chromosome. , 2006, Molecular biology and evolution.

[80]  Daniel W. Udwary,et al.  Type III polyketide synthase beta-ketoacyl-ACP starter unit and ethylmalonyl-CoA extender unit selectivity discovered by Streptomyces coelicolor genome mining. , 2006, Journal of the American Chemical Society.

[81]  D. Hopwood,et al.  Soil to genomics: the Streptomyces chromosome. , 2006, Annual review of genetics.

[82]  Jean-Luc Pernodet,et al.  Multiple biosynthetic and uptake systems mediate siderophore-dependent iron acquisition in Streptomyces coelicolor A3(2) and Streptomyces ambofaciens ATCC 23877. , 2006, Microbiology.

[83]  Paul R Jensen,et al.  Biogeography of the marine actinomycete Salinispora. , 2006, Environmental microbiology.

[84]  René L. Warren,et al.  The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic powerhouse , 2006, Proceedings of the National Academy of Sciences.

[85]  V. Barbe,et al.  Intraspecific Variability of the Terminal Inverted Repeats of the Linear Chromosome of Streptomyces ambofaciens , 2006, Journal of bacteriology.

[86]  C. Farnet,et al.  Genomic Analyses Lead to Novel Secondary Metabolites , 2006, The Journal of Antibiotics.

[87]  Thomas Börner,et al.  Natural Biocombinatorics in the Polyketide Synthase Genes of the Actinobacterium Streptomyces avermitilis , 2006, PLoS Comput. Biol..

[88]  Johan A. Kers,et al.  Evolution of plant pathogenicity in Streptomyces. , 2006, Annual review of phytopathology.

[89]  H. Ikeda,et al.  Geosmin Biosynthesis in Streptomyces avermitilis. Molecular Cloning, Expression, and Mechanistic Study of the Germacradienol/Geosmin Synthase , 2006, The Journal of Antibiotics.

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

[91]  E. Takano.  Gamma-butyrolactones: Streptomyces signalling molecules regulating antibiotic production and differentiation. , 2006, Current opinion in microbiology.

[92]  K. Yazawa,et al.  Transvalencin Z, a New Antimicrobial Compound with Salicylic Acid Residue from Nocardia transvalensis IFM 10065 , 2006, The Journal of Antibiotics.

[93]  Ben Shen,et al.  Microbial genomics for the improvement of natural product discovery. , 2006, Current opinion in microbiology.

[94]  S. Ōmura,et al.  Lariatins, antimycobacterial peptides produced by Rhodococcus sp. K01-B0171, have a lasso structure. , 2006, Journal of the American Chemical Society.

[95]  H. Ikeda,et al.  A gene cluster for biosynthesis of the sesquiterpenoid antibiotic pentalenolactone in Streptomyces avermitilis. , 2006, Biochemistry.

[96]  D. Cane,et al.  Genome mining in Streptomyces coelicolor: molecular cloning and characterization of a new sesquiterpene synthase. , 2006, Journal of the American Chemical Society.

[97]  Arsen O. Batagov,et al.  Identification of erythrobactin, a hydroxamate‐type siderophore produced by Saccharopolyspora erythraea , 2006, Letters in applied microbiology.

[98]  Marcos Catanho,et al.  GenoMycDB: a database for comparative analysis of mycobacterial genes and genomes. , 2006, Genetics and molecular research : GMR.

[99]  Maureen L. Coleman,et al.  Genomic Islands and the Ecology and Evolution of Prochlorococcus , 2006, Science.

[100]  S. Ōmura,et al.  Isolation and Identification of Three New 5-Alkenyl-3,3(2H)-furanones from Two Streptomyces species using a Genomic Screening Approach , 2006, The Journal of Antibiotics.

[101]  D. Oh,et al.  Cyanosporasides A and B, chloro- and cyano-cyclopenta[a]indene glycosides from the marine actinomycete "Salinispora pacifica". , 2006, Organic letters.

[102]  H. Kwon,et al.  Actinofuranones A and B, polyketides from a marine-derived bacterium related to the genus streptomyces (actinomycetales). , 2006, Journal of natural products.

[103]  G. Challis,et al.  Evidence for the Unusual Condensation of a Diketide with a Pentulose in the Methylenomycin Biosynthetic Pathway of Streptomyces coelicolor A3(2) , 2005, Chembiochem : a European journal of chemical biology.

[104]  S. Horinouchi,et al.  Biosynthesis of Hexahydroxyperylenequinone Melanin via Oxidative Aryl Coupling by Cytochrome P-450 in Streptomyces griseus , 2005, Journal of bacteriology.

[105]  Sylvie Lautru,et al.  Discovery of a new peptide natural product by Streptomyces coelicolor genome mining , 2005, Nature chemical biology.

[106]  William Fenical,et al.  Salinispora arenicola gen. nov., sp. nov. and Salinispora tropica sp. nov., obligate marine actinomycetes belonging to the family Micromonosporaceae. , 2005, International journal of systematic and evolutionary microbiology.

[107]  P. Leadlay,et al.  A New Modular Polyketide Synthase in the Erythromycin Producer Saccharopolyspora erythraea , 2005, Journal of Molecular Microbiology and Biotechnology.

[108]  Eriko Takano,et al.  A bacterial hormone (the SCB1) directly controls the expression of a pathway‐specific regulatory gene in the cryptic type I polyketide biosynthetic gene cluster of Streptomyces coelicolor , 2005, Molecular microbiology.

[109]  Emmanuel Zazopoulos,et al.  Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel antifungal agent, as an example. , 2005, Journal of natural products.

[110]  Y. Ohizumi,et al.  Brasilibactin A, a cytotoxic compound from actinomycete Nocardia brasiliensis. , 2005, Journal of natural products.

[111]  T. Beppu,et al.  Light-Induced Carotenogenesis in Streptomyces coelicolor A3(2): Identification of an Extracytoplasmic Function Sigma Factor That Directs Photodependent Transcription of the Carotenoid Biosynthesis Gene Cluster , 2005, Journal of bacteriology.

[112]  S. Ōmura,et al.  The life and times of ivermectin — a success story , 2004, Nature Reviews Microbiology.

[113]  G. Challis,et al.  Identification of a cluster of genes that directs desferrioxamine biosynthesis in Streptomyces coelicolor M145. , 2004, Journal of the American Chemical Society.

[114]  Daniel W. Udwary,et al.  Crystal Structure of a Bacterial Type III Polyketide Synthase and Enzymatic Control of Reactive Polyketide Intermediates* , 2004, Journal of Biological Chemistry.

[115]  M. Hattori,et al.  The complete genomic sequence of Nocardia farcinica IFM 10152. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[116]  H. Kinashi,et al.  Two Chimeric Chromosomes of Streptomyces coelicolor A3(2) Generated by Single Crossover of the Wild-Type Chromosome and Linear Plasmid SCP1 , 2004, Journal of bacteriology.

[117]  M. Hudson,et al.  The SapB morphogen is a lantibiotic-like peptide derived from the product of the developmental gene ramS in Streptomyces coelicolor. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[118]  Luiz R Nunes,et al.  The genome sequence of the gram-positive sugarcane pathogen Leifsonia xyli subsp. xyli. , 2004, Molecular plant-microbe interactions : MPMI.

[119]  P. Dürre,et al.  The Complete Genome Sequence of Propionibacterium Acnes, a Commensal of Human Skin , 2004, Science.

[120]  G. Carter,et al.  Diazepinomicin, a new antimicrobial alkaloid from a marine Micromonospora sp. , 2004, Journal of natural products.

[121]  S. Ōmura,et al.  Antiparasitic agents produced by microorganisms , 2004, Proceedings of the Japan Academy. Series B, Physical and Biological Sciences.

[122]  R. Dhakal,et al.  Genome-inspired search for new antibiotics. Isolation and structure determination of new 28-membered polyketide macrolactones, halstoctacosanolides A and B, from Streptomyces halstedii HC34 , 2004 .

[123]  B. Barrell,et al.  SCP1, a 356 023 bp linear plasmid adapted to the ecology and developmental biology of its host, Streptomyces coelicolor A3(2) , 2004, Molecular microbiology.

[124]  S. Mangenot,et al.  Functional Angucycline-Like Antibiotic Gene Cluster in the Terminal Inverted Repeats of the Streptomyces ambofaciens Linear Chromosome , 2004, Antimicrobial Agents and Chemotherapy.

[125]  K. Haahtela,et al.  Frankiamide: A Structural Revision to Demethyl (C-11) Cezomycin , 2003 .

[126]  S. Miyoshi,et al.  Identification and Characterization of Genes Required for Biosynthesis and Transport of the Siderophore Vibrioferrin in Vibrio parahaemolyticus , 2003, Journal of bacteriology.

[127]  B. Barrell,et al.  The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129. , 2003, Nucleic acids research.

[128]  A. Goesmann,et al.  The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of L-aspartate-derived amino acids and vitamins. , 2003, Journal of biotechnology.

[129]  B. Moore,et al.  Expression and characterization of the type III polyketide synthase 1,3,6,8-tetrahydroxynaphthalene synthase from Streptomyces coelicolor A3(2) , 2003, Journal of Industrial Microbiology and Biotechnology.

[130]  H. Ikeda,et al.  Cytochrome p450 complement (CYPome) of the avermectin-producer Streptomyces avermitilis and comparison to that of Streptomyces coelicolor A3(2). , 2003, Biochemical and biophysical research communications.

[131]  K. Hiratsu,et al.  The large linear plasmid pSLA2‐L of Streptomyces rochei has an unusually condensed gene organization for secondary metabolism , 2003, Molecular microbiology.

[132]  Yoshiyuki Sakaki,et al.  Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis , 2003, Nature Biotechnology.

[133]  S. Bentley,et al.  Streptomyces coelicolor A3(2) plasmid SCP2*: deductions from the complete sequence. , 2003, Microbiology.

[134]  G. Challis,et al.  PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[135]  Brian O. Bachmann,et al.  A genomics-guided approach for discovering and expressing cryptic metabolic pathways , 2003, Nature Biotechnology.

[136]  Jason Micklefield,et al.  Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor. , 2002, Chemistry & biology.

[137]  Ralph Kirby,et al.  Once the circle has been broken: dynamics and evolution of Streptomyces chromosomes. , 2002, Trends in genetics : TIG.

[138]  William Fenical,et al.  Widespread and Persistent Populations of a Major New Marine Actinomycete Taxon in Ocean Sediments , 2002, Applied and Environmental Microbiology.

[139]  U. Gräfe,et al.  Asterobactin, a new siderophore group antibiotic from Nocardia asteroides. , 2002, The Journal of antibiotics.

[140]  B. Wilkinson,et al.  Identification and cloning of a type III polyketide synthase required for diffusible pigment biosynthesis in Saccharopolyspora erythraea ‡ , 2002, Molecular microbiology.

[141]  B. Barrell,et al.  Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2) , 2002, Nature.

[142]  Manor Askenazi,et al.  Genome Sequence of the Plant Pathogen and Biotechnology Agent Agrobacterium tumefaciens C58 , 2001, Science.

[143]  J A Eisen,et al.  The Genome of the Natural Genetic Engineer Agrobacterium tumefaciens C58 , 2001, Science.

[144]  M. Watve,et al.  How many antibiotics are produced by the genus Streptomyces? , 2001, Archives of Microbiology.

[145]  Yoshiyuki Sakaki,et al.  Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[146]  S. Cohen,et al.  Terminal proteins essential for the replication of linear plasmids and chromosomes in Streptomyces. , 2001, Genes & development.

[147]  B. Moore,et al.  Discovery of a New Bacterial Polyketide Biosynthetic Pathway , 2001, Chembiochem : a European journal of chemical biology.

[148]  M. Redenbach,et al.  Chromosome topology and genome size of selected actinomycetes species , 2000, Antonie van Leeuwenhoek.

[149]  H. Blöcker,et al.  The myxochelin iron transport regulon of the myxobacterium Stigmatella aurantiaca Sg a15. , 2000, European journal of biochemistry.

[150]  K. Poralla,et al.  Hopanoids are formed during transition from substrate to aerial hyphae in Streptomyces coelicolor A3(2). , 2000, FEMS microbiology letters.

[151]  G. Challis,et al.  Coelichelin, a new peptide siderophore encoded by the Streptomyces coelicolor genome: structure prediction from the sequence of its non-ribosomal peptide synthetase. , 2000, FEMS microbiology letters.

[152]  M. Bibb,et al.  Purification and Structural Determination of SCB1, a γ-Butyrolactone That Elicits Antibiotic Production inStreptomyces coelicolor A3(2)* , 2000, The Journal of Biological Chemistry.

[153]  M. Tsuda,et al.  Nocarasins A−C and Brasiliquinone D, New Metabolites from the Actinomycete Nocardia brasiliensis , 1999 .

[154]  D. Hopwood,et al.  Forty years of genetics with Streptomyces: from in vivo through in vitro to in silico. , 1999, Microbiology.

[155]  Isao Fujii,et al.  A new pathway for polyketide synthesis in microorganisms , 1999, Nature.

[156]  S Omura,et al.  Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[157]  C. Walsh,et al.  Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. , 1998, Chemistry & biology.

[158]  T. Ishida,et al.  Brasilicardin A. A Novel Tricyclic Metabolite with Potent Immunosuppressive Activity from Actinomycete Nocardiabrasiliensis. , 1998, The Journal of organic chemistry.

[159]  Yuemao Shen,et al.  Engineered biosynthesis of novel polyketides from Streptomyces spore pigment polyketide synthases , 1998 .

[160]  B. Barrell,et al.  Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence , 1998, Nature.

[161]  S. Salzberg,et al.  Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi , 1997, Nature.

[162]  B. Wilkinson,et al.  Biosynthesis of Erythromycin and Rapamycin. , 1997, Chemical reviews.

[163]  U. Gräfe,et al.  Nocardicyclins A and B: new anthracycline antibiotics produced by Nocardia pseudobrasiliensis. , 1997, The Journal of antibiotics.

[164]  E. Stackebrandt,et al.  Phylogenetic analysis of the genus Desulfotomaculum: evidence for the misclassification of Desulfotomaculum guttoideum and description of Desulfotomaculum orientis as Desulfosporosinus orientis gen. nov., comb. nov. , 1997, International journal of systematic bacteriology.

[165]  J. Lancelin,et al.  Revised 1H and 13C NMR Assignments of the Polyene Antibiotic Filipin III , 1997 .

[166]  H. Nagata,et al.  Lymphostin (LK6-A), a novel immunosuppressant from Streptomyces sp. KY11783: structural elucidation. , 1997, The Journal of antibiotics.

[167]  M. Tsuda,et al.  Brasilidine A, a new cytotoxic isonitrile-containing indole alkaloid from the actinomycete Nocardia brasiliensis. , 1997, Journal of natural products.

[168]  Kobayashi Junichi,et al.  Brasilinolide A, new immunosuppressive macrolide from actinomycete Nocardia brasiliensis , 1996 .

[169]  P. Shipley,et al.  The thiostrepton-resistance-encoding gene in Streptomyces laurentii is located within a cluster of ribosomal protein operons. , 1995, Gene.

[170]  R. Fleischmann,et al.  Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. , 1995, Science.

[171]  H. Ikeda,et al.  Transposon mutagenesis by Tn4560 and applications with avermectin-producing Streptomyces avermitilis , 1993, Journal of bacteriology.

[172]  J. Kobayashi,et al.  SO-75R1, a new mutactimycin derivative produced by Nocardia brasiliensis. , 1992, The Journal of antibiotics.

[173]  Gerd Mayer,et al.  Streptomycin biosynthesis and its regulation in Streptomycetes. , 1992, Gene.

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

[175]  P. Jensen,et al.  Distribution of actinomycetes in near-shore tropical marine sediments , 1991, Applied and environmental microbiology.

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

[177]  H. Ikeda,et al.  Production of ‘hybrid’ antibiotics by genetic engineering , 1985, Nature.

[178]  M. Hashimoto,et al.  Letter: Nocardicin A and B, novel monocyclic beta-lactam antibiotics from a Nocardia species. , 1976, Journal of the American Chemical Society.

[179]  S. Waksman.  Streptomycin: background, isolation, properties, and utilization. , 1953, Science.

[180]  L. Katz.  The DEBS paradigm for type I modular polyketide synthases and beyond. , 2009, Methods in enzymology.

[181]  M. Marahiel,et al.  Chapter 13. Nonribosomal peptide synthetases mechanistic and structural aspects of essential domains. , 2009, Methods in enzymology.

[182]  M. Pátek,et al.  Biodegradation potential of the genus Rhodococcus. , 2009, Environment international.

[183]  B. Moore,et al.  Discovery and characterization of a marine bacterial SAM-dependent chlorinase. , 2008, Nature chemical biology.

[184]  J. Pezzuto,et al.  Saliniketals A and B, bicyclic polyketides from the marine actinomycete Salinispora arenicola. , 2007, Journal of natural products.

[185]  T. Eguchi,et al.  The Complete Biosynthetic Gene Cluster of the 28-Membered Polyketide Macrolactones, Halstoctacosanolides, from Streptomyces halstedii HC34 , 2006, The Journal of Antibiotics.

[186]  János Bérdy,et al.  Bioactive microbial metabolites. , 2005, The Journal of antibiotics.

[187]  M. Bibb,et al.  Analysis of the prodiginine biosynthesis gene cluster of Streptomyces coelicolor A3(2): new mechanisms for chain initiation and termination in modular multienzymes. , 2001, Chemistry & biology.

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

[189]  G. Challis,et al.  Incorporation of [U-13C]glycerol defines plausible early steps for the biosynthesis of methylenomycin A in Streptomyces coelicolor A3(2) , 2001 .

[190]  H. Lee,et al.  A sigmaB-like factor responsible for carotenoid biosynthesis in Streptomyces griseus. , 2001, Journal of molecular microbiology and biotechnology.

[191]  T. Kieser.  Practical streptomyces genetics , 2000 .

[192]  M. Tsuda,et al.  Brasiliquinones A-C, new cytotoxic benz [a] anthraquinones with an ethyl group at C-3 from actinomycete Nocardia brasiliensis , 1996 .

[193]  F. Hauser,et al.  A new route to benzo[a]naphthacene-8,13-diones: synthesis and revision of the structure proposed for G2N , 1990 .

[194]  D. Labeda.  Transfer of the Type Strain of Streptomyces erythraeus (Waksman 1923) Waksman and Henrici 1948 to the Genus Saccharopolyspora Lacey and Goodfellow 1975 as Saccharopolyspora erythraea sp. nov., and Designation of a Neotype Strain for Streptomyces erythraeus , 1987 .

[195]  H. Kinashi,et al.  Giant linear plasmids in Streptomyces which code for antibiotic biosynthesis genes , 1987, Nature.

[196]  D. Hopwood,et al.  Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host , 1984, Nature.