Genome mining of the Streptomycesavermitilis genome and development of genome-minimized hosts for heterologous expression of biosynthetic gene clusters

To date, several actinomycete genomes have been completed and annotated. Among them, Streptomyces microorganisms are of major pharmaceutical interest because they are a rich source of numerous secondary metabolites. S. avermitilis is an industrial microorganism used for the production of an anthelmintic agent, avermectin, which is a commercially important antiparasitic agent in human and veterinary medicine, and agricultural pesticides. Genome analysis of S. avermitilis provides significant information for not only industrial applications but also understanding the features of this genus. On genome mining of S. avermitilis, the microorganism has been found to harbor at least 38 secondary metabolic gene clusters and 46 insertion sequence (IS)-like sequences on the genome, which have not been searched so far. A significant use of the genome data of Streptomyces microorganisms is the construction of a versatile host for heterologous expression of exogenous biosynthetic gene clusters by genetic engineering. Since S. avermitilis is used as an industrial microorganism, the microorganism is already optimized for the efficient supply of primary metabolic precursors and biochemical energy to support multistep biosynthesis. The feasibility of large-deletion mutants of S. avermitilis has been confirmed by heterologous expression of more than 20 exogenous biosynthetic gene clusters.

[1]  H. Ikeda,et al.  Nocardamin Production by Streptomyces avermitilis , 2009 .

[2]  M. Komatsu,et al.  Characterization of a silent sesquiterpenoid biosynthetic pathway in Streptomyces avermitilis controlling epi‐isozizaene albaflavenone biosynthesis and isolation of a new oxidized epi‐isozizaene metabolite , 2011, Microbial biotechnology.

[3]  H. Ikeda,et al.  Genome mining in streptomyces. Discovery of an unprecedented P450-catalyzed oxidative rearrangement that is the final step in the biosynthesis of pentalenolactone. , 2011, Journal of the American Chemical Society.

[4]  H. Ikeda,et al.  Total synthesis and absolute configuration of avenolide, extracellular factor in Streptomyces avermitilis , 2011, The Journal of Antibiotics.

[5]  E. Galinski,et al.  Characterization of genes for the biosynthesis of the compatible solute ectoine from Marinococcus halophilus and osmoregulated expression in Escherichia coli. , 1997, Microbiology.

[6]  H. Ikeda,et al.  Crystal Structures of Cytochrome P450 105P1 from Streptomyces avermitilis: Conformational Flexibility and Histidine Ligation State , 2008, Journal of bacteriology.

[7]  R. Breitling,et al.  The Sequence of a 1.8-Mb Bacterial Linear Plasmid Reveals a Rich Evolutionary Reservoir of Secondary Metabolic Pathways , 2010, Genome biology and evolution.

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

[9]  Bo Zhang,et al.  Genome Sequence of the Milbemycin-Producing Bacterium Streptomycesbingchenggensis , 2010, Journal of bacteriology.

[10]  Bradley S Moore,et al.  Genomic basis for natural product biosynthetic diversity in the actinomycetes. , 2009, Natural product reports (Print).

[11]  Erhard Bremer,et al.  Osmotically Regulated Synthesis of the Compatible Solute Ectoine in Bacillus pasteurii and Related Bacillus spp , 2002, Applied and Environmental Microbiology.

[12]  R. Loria,et al.  Streptomyces scabies 87-22 contains a coronafacic acid-like biosynthetic cluster that contributes to plant-microbe interactions. , 2010, Molecular plant-microbe interactions : MPMI.

[13]  S. Chung.  Tn4556, a 6.8-kilobase-pair transposable element of Streptomyces fradiae , 1987, Journal of bacteriology.

[14]  A. Lapidot,et al.  The Structure and Biosynthesis of New Tetrahydropyrimidine Derivatives in Actinomycin D Producer Streptomyces parvulus , 1988 .

[15]  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.

[16]  J. Poulain,et al.  Complete Genome Sequence of Streptomyces cattleya NRRL 8057, a Producer of Antibiotics and Fluorometabolites , 2011, Journal of bacteriology.

[17]  H. Ikeda,et al.  Crystal Structure of the Non-heme Iron Dioxygenase PtlH in Pentalenolactone Biosynthesis* , 2007, Journal of Biological Chemistry.

[18]  Joern Hopke,et al.  Genetically Modified Bacterial Strains and Novel Bacterial Artificial Chromosome Shuttle Vectors for Constructing Environmental Libraries and Detecting Heterologous Natural Products in Multiple Expression Hosts , 2004, Applied and Environmental Microbiology.

[19]  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.

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

[21]  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.

[22]  A. Lapidot,et al.  The structure and biosynthesis of new tetrahydropyrimidine derivatives in actinomycin D producer Streptomyces parvulus. Use of 13C- and 15N-labeled L-glutamate and 13C and 15N NMR spectroscopy. , 1988, The Journal of biological chemistry.

[23]  H. Ikeda,et al.  Regio- and Stereospecificity of Filipin Hydroxylation Sites Revealed by Crystal Structures of Cytochrome P450 105P1 and 105D6 from Streptomyces avermitilis* , 2010, The Journal of Biological Chemistry.

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

[25]  J. J. Nieto,et al.  Characterization of the genes for the biosynthesis of the compatible solute ectoine in the moderately halophilic bacterium Halomonas elongata DSM 3043. , 1998, Systematic and applied microbiology.

[26]  M. Bibb,et al.  Genome-wide analysis of the role of GlnR in Streptomyces venezuelae provides new insights into global nitrogen regulation in actinomycetes , 2011, BMC Genomics.

[27]  Junko Hashimoto,et al.  Engineered Streptomyces avermitilis host for heterologous expression of biosynthetic gene cluster for secondary metabolites. , 2013, ACS synthetic biology.

[28]  H. Mishima,et al.  Milbemycins, a new family of macrolide antibiotics: fermentation, isolation and physico-chemical properties. , 1980, The Journal of antibiotics.

[29]  M. Morgenstern,et al.  A Streptomyces avermitilis gene encoding a 4-hydroxyphenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli , 1994, Journal of bacteriology.

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

[31]  H. Ikeda,et al.  Avenolide, a Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis , 2011, Proceedings of the National Academy of Sciences.

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

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

[34]  Zhihao Hu,et al.  Process and Metabolic Strategies for Improved Production of Escherichia coli-Derived 6-Deoxyerythronolide B , 2002, Applied and Environmental Microbiology.

[35]  B. Shen,et al.  Engineered production of iso-migrastatin in heterologous Streptomyces hosts. , 2009, Bioorganic & medicinal chemistry.

[36]  H. Ikeda,et al.  Genetic studies of avermectin biosynthesis in Streptomyces avermitilis , 1987, Journal of bacteriology.

[37]  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.

[38]  E. Takano,et al.  Analysis of two additional signaling molecules in Streptomyces coelicolor and the development of a butyrolactone-specific reporter system. , 2009, Chemistry & biology.

[39]  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.

[40]  H. Ikeda,et al.  Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlI, a cytochrome P450 of Streptomyces avermitilis. , 2006, Journal of the American Chemical Society.

[41]  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.

[42]  P. Solenberg,et al.  Method for selection of transposable DNA and characterization of a new insertion sequence, IS493, from Streptomyces lividans , 1989, Journal of bacteriology.

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

[44]  M. Komatsu,et al.  Pentalenic acid is a shunt metabolite in the biosynthesis of the pentalenolactone family of metabolites: hydroxylation of 1-deoxypentalenic acid mediated by CYP105D7 (SAV_7469) of Streptomyces avermitilis , 2011, The Journal of Antibiotics.

[45]  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.

[46]  G. Malin,et al.  Induction of synthesis of tetrahydropyrimidine derivatives in Streptomyces strains and their effect on Escherichia coli in response to osmotic and heat stress , 1996, Journal of bacteriology.

[47]  H. Ikeda,et al.  Molecular cloning of the gene cluster for lariatin biosynthesis of Rhodococcus jostii K01-B0171 , 2012, Applied Microbiology and Biotechnology.

[48]  H. Ikeda,et al.  Genome mining in Streptomyces. Elucidation of the role of Baeyer-Villiger monooxygenases and non-heme iron-dependent dehydrogenase/oxygenases in the final steps of the biosynthesis of pentalenolactone and neopentalenolactone. , 2011, Biochemistry.

[49]  M. Siegel,et al.  LL-F28249 antibiotic complex: a new family of antiparasitic macrocyclic lactones. Isolation, characterization and structures of LL-F28249 alpha, beta, gamma, lambda. , 1988, The Journal of antibiotics.

[50]  M. Komatsu,et al.  Genome mining in Streptomyces avermitilis: cloning and characterization of SAV_76, the synthase for a new sesquiterpene, avermitilol. , 2010, Journal of the American Chemical Society.

[51]  Satoshi Omura,et al.  Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism , 2010, Proceedings of the National Academy of Sciences.

[52]  H. Ikeda,et al.  Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlH, a non-heme iron dioxygenase of Streptomyces avermitilis. , 2006, Journal of the American Chemical Society.

[53]  S. Ōmura,et al.  Avermectins, New Family of Potent Anthelmintic Agents: Producing Organism and Fermentation , 1979, Antimicrobial Agents and Chemotherapy.