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Synthetic Biology Tools for Novel Secondary Metabolite Discovery in Streptomyces

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초록

Streptomyces are attractive microbial cell factories that have industrial capability to produce a wide array of bioactive secondary metabolites. However, the genetic potential of the Streptomyces species has not been fully utilized because most of their secondary metabolite biosynthetic gene clusters (SM-BGCs) are silent under laboratory culture conditions. In an effort to activate SM-BGCs encoded in Streptomyces genomes, synthetic biology has emerged as a robust strategy to understand, design, and engineer the biosynthetic capability of Streptomyces secondary metabolites. In this regard, diverse synthetic biology tools have been developed for Streptomyces species with technical advances in DNA synthesis, sequencing, and editing. Here, we review recent progress in the development of synthetic biology tools for the production of novel secondary metabolites in Streptomyces, including genomic elements and genome engineering tools for Streptomyces, the heterologous gene expression strategy of designed biosynthetic gene clusters in the Streptomyces chassis strain, and future directions to expand diversity of novel secondary metabolites.

Abstract

Streptomyces are attractive microbial cell factories that have industrial capability to produce a wide array of bioactive secondary metabolites. However, the genetic potential of the Streptomyces species has not been fully utilized because most of their secondary metabolite biosynthetic gene clusters (SM-BGCs) are silent under laboratory culture conditions. In an effort to activate SM-BGCs encoded in Streptomyces genomes, synthetic biology has emerged as a robust strategy to understand, design, and engineer the biosynthetic capability of Streptomyces secondary metabolites. In this regard, diverse synthetic biology tools have been developed for Streptomyces species with technical advances in DNA synthesis, sequencing, and editing. Here, we review recent progress in the development of synthetic biology tools for the production of novel secondary metabolites in Streptomyces, including genomic elements and genome engineering tools for Streptomyces, the heterologous gene expression strategy of designed biosynthetic gene clusters in the Streptomyces chassis strain, and future directions to expand diversity of novel secondary metabolites.

참고문헌 (140)

  1. Ohnishi Y, "Genome sequence of the streptomycinproducing microorganism Streptomyces griseus IFO 13350", J. Bacteriol, 190, pp.4050~4060 (2008)
  2. Khan ST, "Streptomyces associated with a marine sponge Haliclona sp,; biosynthetic genes for secondary metabolites and products", Environ. Microbiol, 13, pp.391~403 (2011)
  3. Onaka H., "Novel antibiotic screening methods to awaken silent or cryptic secondary metabolic pathways in actinomycetes", J. Antibiot. (Tokyo), 70, pp.865~870 (2017)
  4. Lim FY, "Toward awakening cryptic secondary metabolite gene clusters in filamentous fungi", Methods Enzymol, 517, pp.303~324 (2012)
  5. Medema MH, "The future of industrial antibiotic production : from random mutagenesis to synthetic biology", Bioeng. Bugs, 2, pp.230~233 (2011)
  6. Nguyen QT, "Metabolomics methods for the synthetic biology of secondary metabolism", FEBS Lett, 586, pp.2177~2183 (2012)
  7. Yang YH, "Rapid functional screening of Streptomyces coelicolor regulators by use of a pH indicator and application to the MarR-like regulator AbsC", Appl. Environ. Microbiol, 76, pp.3645~3656 (2010)
  8. Myronovskyi M, "Native and engineered promoters in natural product discovery", Nat. Prod. Rep, 33, pp.1006~1019 (2016)
  9. Ziemert N, "The evolution of genome mining in microbes-a review", Nat. Prod. Rep, 33, pp.988~1005 (2016)
  10. Harrison J, "Recently published Streptomyces genome sequences", Microb. Biotechnol, 7, pp.373~380 (2014)
  11. Bentley SD, "Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2)", Nature, 417, pp.141~147 (2002)
  12. Komaki H, "Diversity of nonribosomal peptide synthetase and polyketide synthase gene clusters among taxonomically close Streptomyces strains", Sci. Rep, 8, pp.6888~ (2018)
  13. Starcevic A, "ClustScan : an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures", Nucleic Acids Res, 36, pp.6882~6892 (2008)
  14. Li MH, "Automated genome mining for natural products", BMC Bioinformatics, 10, pp.185~ (2009)
  15. Skinnider MA, "Genomes to natural products prediction informatics for secondary metabolomes(PRISM)", Nucleic Acids Res, 43, pp.9645~9662 (2015)
  16. Blin K, "antiSMASH 4,0-improvements in chemistry prediction and gene cluster boundary identification", Nucleic Acids Res, 45, pp.W36~W41 (2017)
  17. Weber T, "The secondary metabolite bioinformatics portal : computational tools to facilitate synthetic biology of secondary metabolite production", Synth. Syst. Biotechnol, 1, pp.69~79 (2016)
  18. Low ZJ, "Identification of a biosynthetic gene cluster for the polyene macrolactam sceliphrolactam in a Streptomyces strain isolated from mangrove sediment", Sci. Rep, 8, pp.1594~ (2018)
  19. Jia N, "Complete genome sequencing and antibiotics biosynthesis pathways analysis of Streptomyces lydicus 103", Sci. Rep, 7, pp.44786~ (2017)
  20. Zhang G, "Genome-wide analysis reveals the secondary metabolome in Streptomyces kanasensis ZX01", Genes (Basel), 8, pp.346~ (2017)
  21. Ansari MZ, "NRPS-PKS : a knowledge-based resource for analysis of NRPS", PKS megasynthases, 2004, pp.32, W405~W413
  22. Kim MS, "Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis", Microb. Cell Fact, 16, pp.9~ (2017)
  23. Ikeda H, "Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis", Nat. Biotechnol, 21, pp.526~531 (2003)
  24. Bode HB, "Big effects from small changes : possible ways to explore nature’s chemical diversity", Chembiochem, 3, pp.619~627 (2002)
  25. Marmann A, "Co-cultivation--a powerful emerging tool for enhancing the chemical diversity of microorganisms", Mar. Drugs, 12, pp.1043~1065 (2014)
  26. Baral B, "Activation of microbial secondary metabolic pathways : Avenues and challenges", Synth. Syst. Biotechnol, 3, pp.163~178 (2018)
  27. King AA, "The expression of the Escherichia coli lacZ gene in Streptomyces", J. Gen. Microbiol, 132, pp.1739~1752 (1986)
  28. Lussier FX, "Adaptation of the highly productive T7 expression system to Streptomyces lividans", Appl. Environ. Microbiol, 76, pp.967~970 (2010)
  29. Mitra A, "Occurrence, divergence and evolution of intrinsic terminators across eubacteria", Genomics, 94, pp.110~116 (2009)
  30. Bibb MJ, "The mRNA for the 23S rRNA methylase encoded by the ermE gene of Saccharopolyspora erythraea is translated in the absence of a conventional ribosome-binding site", Mol. Microbiol, 14, pp.533~545 (1994)
  31. Bibb MJ, "Cloning and analysis of the promoter region of the erythromycin resistance gene(ermE)of Streptomyces erythraeus", Gene, 38, pp.215~226 (1985)
  32. Kieser T, "Practical Streptomyces Genetics" (2000), John Innes Foundation
  33. Wang W, "An engineered strong promoter for Streptomycetes", Appl. Environ. Microbiol, 79, pp.4484~4492 (2013)
  34. Labes G, "Isolation and characterization of a strong promoter element from the Streptomyces ghanaensis phage I19 using the gentamicin resistance gene(aacC1)of Tn 1696 as reporter", Microbiology, 143, pp.1503~1512 (1997)
  35. Shao Z, "Refactoring the silent spectinabilin gene cluster using a plug-and-play scaffold", ACS Synth. Biol, 2, pp.662~669 (2013)
  36. Sohoni SV, "Synthetic promoter library for modulation of actinorhodin production in Streptomyces coelicolor A3(2)", PLoS One, 9, pp.e99701~ (2014)
  37. Seghezzi N, "The construction of a library of synthetic promoters revealed some specific features of strong Streptomyces promoters", Appl. Microbiol. Biotechnol, 90, pp.615~623 (2011)
  38. Luo Y, "Systematic identification of a panel of strong constitutive promoters from Streptomyces albus", ACS Synth. Biol, 4, pp.1001~1010 (2015)
  39. Li S, "Genomewide identification and evaluation of constitutive promoters in Streptomycetes", Microb. Cell Fact, 14, pp.172~ (2015)
  40. Murakami T, "Thiostreptoninduced gene expression in Streptomyces lividans", J. Bacteriol, 171, pp.1459~1466 (1989)
  41. Takano E, "Construction of thiostrepton-inducible, high-copy-number expression vectors for use in Streptomyces spp", Gene, 166, pp.133~137 (1995)
  42. Huang H, "One-step high-efficiency CRISPR", Cas9-mediated genome editing in Streptomyces, 2015, pp.47, 231~243
  43. Rodriguez-Garcia A, "Natural and synthetic tetracyclineinducible promoters for use in the antibiotic-producing bacteria Streptomyces", Nucleic Acids Res, 33, pp.e87~ (2005)
  44. Horbal L, "Novel and tightly regulated resorcinol and cumate-inducible expression systems for Streptomyces and other actinobacteria", Appl. Microbiol. Biotechnol, 98, pp.8641~8655 (2014)
  45. Herai S, "Hyper-inducible expression system for Streptomycetes", Proc. Natl. Acad. Sci. USA, 101, pp.14031~14035 (2004)
  46. Noguchi Y, "Development of a strictly regulated xylose-induced expression system in Streptomyces", Microb. Cell Fact, 17, pp.151~ (2018)
  47. Hindle Z, "Substrate induction and catabolite repression of the Streptomyces coelicolor glycerol operon are mediated through the GylR protein", Mol. Microbiol, 12, pp.737~745 (1994)
  48. Ward JM, "Construction and characterisation of a series of multicopy promoter-probe plasmid vectors for Streptomyces using the aminoglycoside phosphotransferase gene from Tn5 as indicator", Mol. Gen. Genet, 203, pp.468~478 (1986)
  49. Pulido D, "A Bacillus subtilis phage phi 29 transcription terminator is efficiently recognized in Streptomyces lividans", Gene, 56, pp.277~282 (1987)
  50. Cobb RE, "High-efficiency multiplex genome editing of Streptomyces species using an engineered CRISPR", Cas system, 2015, pp.4, 723~728
  51. West S, "Transcriptional termination enhances protein expression in human cells", Mol. Cell, 33, pp.354~364 (2009)
  52. Mapendano CK, "Crosstalk between mRNA 3’ end processing and transcription initiation", Mol. Cell, 40, pp.410~422 (2010)
  53. Dar D, "Term-seq reveals abundant riboregulation of antibiotics resistance in bacteria", Science, 352, pp.aad9822~ (2016)
  54. Lu P, "Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation", Nat. Biotechnol, 25, pp.117~124 (2007)
  55. Jeong Y, "The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2)", Nat. Commun, 7, pp.11605~ (2016)
  56. Makrides SC, "Strategies for achieving high-level expression of genes in Escherichia coli", Microbiol. Rev, 60, pp.512~538 (1996)
  57. Na D, "RBSDesigner : software for designing synthetic ribosome binding sites that yields a desired level of protein expression", Bioinformatics, 26, pp.2633~2634 (2010)
  58. Bai C, "Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces", Proc. Natl. Acad. Sci. USA, 112, pp.12181~12186 (2015)
  59. Yi JS, "A novel approach for gene expression optimization through native promoter and 5’ UTR combinations based on RNA-seq, Ribo-seq, and TSS-seq of Streptomyces coelicolor", ACS Synth. Biol, 6, pp.555~565 (2017)
  60. Janssen GR, "Tandem promoters, tsrp1 and tsrp2, direct transcription of the thiostrepton resistance gene(tsr)of Streptomyces azureus : transcriptional initiation from tsrp2 occurs after deletion of the-35 region", Mol. Gen. Genet, 221, pp.339~346 (1990)
  61. Sohaskey CD, "Tn4556and luciferase : synergistic tools for visualizing transcription in Streptomyces", Gene, 115, pp.67~71 (1992)
  62. Ingram C, "xylE functions as an efficient reporter gene in Streptomyces spp,: use for the study of galP1, a catabolite-controlled promoter", J. Bacteriol, 171, pp.6617~6624 (1989)
  63. Myronovskyi M, "Beta-glucuronidase as a sensitive and versatile reporter in actinomycetes", Appl. Environ Microbiol, 77, pp.5370~5383 (2011)
  64. Flores FJ, "Characterization of the iron-regulated desA promoter of Streptomyces pilosus as a system for controlled gene expression in actinomycetes", Microb. Cell Fact, 2, pp.5~ (2003)
  65. Willemse J, "Imaging of Streptomyces coelicolor A3(2) with reduced autofluorescence reveals a novel stage of FtsZ localization", PLoS One, 4, pp.e4242~ (2009)
  66. Santos-Beneit F, "Green fluorescent protein as a reporter for the spatial and temporal expression of actIII in Streptomyces coelicolor", Arch. Microbiol, 199, pp.875~880 (2017)
  67. Nguyen KD, "Monomeric red fluorescent protein as a reporter for macromolecular localization in Streptomyces coelicolor", Plasmid, 58, pp.167~173 (2007)
  68. Phelan RM, "Development of next generation synthetic biology tools for use in Streptomyces venezuelae", ACS Synth. Biol, 6, pp.159~166 (2017)
  69. Siegl T, "Actinomycetes genome engineering approaches", Antonie Van Leeuwenhoek, 102, pp.503~516 (2012)
  70. Herrmann S, "Site-specific recombination strategies for engineering actinomycete genomes", Appl. Environ. Microbiol, 78, pp.1804~1812 (2012)
  71. Khodakaramian G, "Expression of Cre recombinase during transient phage infection permits efficient marker removal in Streptomyces", Nucleic Acids Res, 34, pp.e20~ (2006)
  72. Zelyas N, "Use of the native flp gene to generate in-frame unmarked mutations in Streptomyces spp", Gene, 443, pp.48~54 (2009)
  73. Barrangou R, "CRISPR provides acquired resistance against viruses in prokaryotes", Science, 315, pp.1709~1712 (2007)
  74. Cong L, "Multiplex genome engineering using CRISPR", Cas systems, 2013, pp.339, 819~823
  75. DiCarlo JE, "Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems", Nucleic Acids Res, 41, pp.4336~4343 (2013)
  76. Friedland AE, "Heritable genome editing in C, elegans via a CRISPR-Cas9 system", Nat. Methods, 10, pp.741~743 (2013)
  77. Jiang W, "RNA-guided editing of bacterial genomes using CRISPRCas systems", Nat. Biotechnol, 31, pp.233~239 (2013)
  78. Li JF, "Multiplex and homologous recombinationmediated genome editing in Arabidopsis and Nicotiana benthamiana using guide RNA and Cas9", Nat. Biotechnol, 31, pp.688~691 (2013)
  79. Jinek M, "A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity", Science, 337, pp.816~821 (2012)
  80. Bibikova M, "Enhancing gene targeting with designed zinc finger nucleases", Science, 300, pp.764~ (2003)
  81. Christian M, "Targeting DNA double-strand breaks with TAL effector nucleases", Genetics, 186, pp.757~761 (2010)
  82. Rouet P, "Introduction of doublestrand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease", Mol. Cell Biol, 14, pp.8096~8106 (1994)
  83. Doudna JA, "Genome editing, The new frontier of genome engineering with CRISPR-Cas9", Science, 346, pp.1258096~ (2014)
  84. Anders C, "Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease", Nature, 513, pp.569~573 (2014)
  85. Mojica FJ, "Short motif sequences determine the targets of the prokaryotic CRISPR defence system", Microbiology, 155, pp.733~740 (2009)
  86. Tong Y, "CRISPR-Cas9 based engineering of actinomycetal genomes", ACS Synth. Biol, 4, pp.1020~1029 (2015)
  87. Zhang MM, "CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters", Nat. Chem. Biol, 13, pp.607~609 (2017)
  88. Zeng H, "Highly efficient editing of the actinorhodin polyketide chain length factor gene in Streptomyces coelicolor M145using CRISPR", Cas9-CodA(sm)combined system, 2015, pp.99, 10575~10585
  89. Li L, "Multiplexed site-specific genome engineering for overproducing bioactive secondary metabolites in actinomycetes", Metab. Eng, 40, pp.80~92 (2017)
  90. Meng J, "Improvement of pristinamycin I(PI)production in Streptomyces pristinaespiralis by metabolic engineering approaches", Synth. Syst. Biotechnol, 2, pp.130~136 (2017)
  91. Qin Z, "Formicamycins, antibacterial polyketides produced by Streptomyces formicae isolated from African Tetraponera plant-ants", Chem. Sci, 8, pp.3218~3227 (2017)
  92. Wang Y, "High-efficiency genome editing of Streptomyces species by an engineered CRISPR", Cas System, 2016, pp.575, 271~284
  93. Jia H, "Development of a CRISPR", Cas9-mediated gene-editing tool in Streptomyces rimosus, 2017, pp.163, 1148~1155
  94. Tao W, "CRISPR", Cas9-based editing of Streptomyces for discovery, characterization, and production of natural products, 2018, pp.9, 1660~
  95. Liu Y, "In vitro CRISPR", Cas9 system for efficient targeted DNA editing, 2015, pp.6, e01714~e01715
  96. Jiang W, "Cas9-assisted targeting of chromosome segments CATCH enables one-step targeted cloning of large gene clusters", Nat. Commun, 6, pp.8101~ (2015)
  97. Kang HS, "Multiplexed CRISPR", Cas9-and TAR-mediated promoter engineering of natural product biosynthetic gene clusters in yeast, 2016, pp.5, 1002~1010
  98. Tao W, "A genomics-led approach to deciphering the mechanism of thiotetronate antibiotic biosynthesis", Chem. Sci, 7, pp.376~385 (2016)
  99. Li L, "aMSGE : advanced multiplex site-specific genome engineering with orthogonal modular recombinases in actinomycetes", Metab. Eng, 52, pp.153~167 (2019)
  100. Qi LS, "Repurposing CRISPR as an RNAguided platform for sequence-specific control of gene expression", Cell, 152, pp.1173~1183 (2013)
  101. Zhao Y, "CRISPR", dCas9-mediated multiplex gene repression in Streptomyces, 2018, pp.13, e1800121~
  102. Xu Z, "Large-scale transposition mutagenesis of Streptomyces coelicolor identifies hundreds of genes influencing antibiotic biosynthesis", Appl. Environ. Microbiol, 83, pp.e02889~ (2017)[DOI]
  103. Komatsu M, "Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism", Proc. Natl. Acad. Sci. USA, 107, pp.2646~2651 (2010)
  104. Gomez-Escribano JP, "Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters", Microb. Biotechnol, 4, pp.207~215 (2011)
  105. Zetsche B, "Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system", Cell, 163, pp.759~771 (2015)
  106. Li L, "CRISPR-Cpf1-assisted multiplex genome editing and transcriptional repression in Streptomyces", Appl. Environ. Microbiol, 84, pp.e00827~e00818 (2018)
  107. Xu M, "Heterologous expression-facilitated natural products’ discovery in actinomycetes", J. Ind. Microbiol. Biotechnol, 46, pp.415~431 (2018)
  108. Liu R, "Streptomyces species : Ideal chassis for natural product discovery and overproduction", Metab. Eng, 50, pp.74~84 (2018)
  109. Nah HJ, "Cloning and heterologous expression of a large-sized natural product biosynthetic gene cluster in Streptomyces Species", Front. Microbiol, 8, pp.394~ (2017)
  110. Rutledge PJ, "Discovery of microbial natural products by activation of silent biosynthetic gene clusters", Nat. Rev. Microbiol, 13, pp.509~523 (2015)
  111. Katz M, "Culture-independent discovery of natural products from soil metagenomes", J. Ind. Microbiol Biotechnol, 43, pp.129~141 (2016)
  112. Pyeon HR, "Heterologous expression of pikromycin biosynthetic gene cluster using Streptomyces artificial chromosome system", Microb. Cell Fact, 16, pp.96~ (2017)
  113. Nah HJ, "Precise cloning and tandem integration of large polyketide biosynthetic gene cluster using Streptomyces artificial chromosome system", Microb. Cell Fact, 14, pp.140~ (2015)
  114. Du D, "Genome engineering and direct cloning of antibiotic gene clusters via phage varphiBT1 integrase-mediated sitespecific recombination in Streptomyces", Sci Rep, 5, pp.8740~ (2015)
  115. Greunke C, "Direct pathway cloning(DiPaC)to unlock natural product biosynthetic potential", Metab. Eng, 47, pp.334~345 (2018)
  116. Shao Z, "Rapid characterization and engineering of natural product biosynthetic pathways via DNA assembler", Mol. Biosyst, 7, pp.1056~1059 (2011)
  117. Fu J, "Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting", Nat. Biotechnol, 30, pp.440~446 (2012)
  118. Yamanaka K, "Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A", Proc. Natl. Acad. Sci. USA, 111, pp.1957~1962 (2014)
  119. Orr-Weaver TL, "Yeast transformation : a model system for the study of recombination", Proc. Natl. Acad. Sci USA, 78, pp.6354~6358 (1981)
  120. Lee NC, "Highly efficient CRISPR", Cas9-mediated TAR cloning of genes and chromosomal loci from complex genomes in yeast, 2015, pp.43, e55~
  121. Bu QT, "Rational construction of genome-reduced and highefficient industrial Streptomyces chassis based on multiple comparative genomic approaches", Microb. Cell Fact, 18, pp.16~ (2019)
  122. Myronovskyi M, "Generation of a clusterfree Streptomyces albus chassis strains for improved heterologous expression of secondary metabolite clusters", Metab. Eng, 49, pp.316~324 (2018)
  123. Xu M, "Functional genome mining for metabolites encoded by large gene clusters through heterologous expression of a whole-genome bacterial artificial chromosome library in Streptomyces spp", Appl. Environ. Microbiol, 82, pp.5795~5805 (2016)
  124. Liu Q, "Development of Streptomyces sp, FR-008 as an emerging chassis", Synth. Syst. Biotechnol, 1, pp.207~214 (2016)
  125. Komatsu M, "Engineered Streptomyces avermitilis host for heterologous expression of biosynthetic gene cluster for secondary metabolites", ACS Synth. Biol, 2, pp.384~396 (2013)
  126. Daniels W, "Finding targets for genome reduction in Streptomyces lividans TK24 using flux balance analysis", IFAC-PapersOnLine, 49, pp.252~257 (2016)
  127. Toro L, "An enhanced genome-scale metabolic reconstruction of Streptomyces clavuligerus identifies novel strain improvement strategies", Bioprocess Biosyst. Eng, 41, pp.657~669 (2018)
  128. Kallifidas D, "Rational engineering of Streptomyces albus J1074 for the overexpression of secondary metabolite gene clusters", Microb. Cell Fact, 17, pp.25~ (2018)
  129. Machado H, "Omics-based natural product discovery and the lexicon of genome mining", Curr. Opin. Microbiol, 39, pp.136~142 (2017)
  130. Ran FA, "In vivo genome editing using Staphylococcus aureus Cas9", Nature, 520, pp.186~191 (2015)
  131. Liu JJ, "CasX enzymes comprise a distinct family of RNA-guided genome editors", Nature, 566, pp.218~223 (2019)
  132. Bikard D, "Programmable repression and activation of bacterial gene expression using an engineered CRISPRCas system", Nucleic Acids Res, 41, pp.7429~7437 (2013)
  133. Siu KH, "Riboregulated toehold-gated gRNA for programmable CRISPR-Cas9 function", Nat. Chem. Biol, 15, pp.217~220 (2019)
  134. Bunet R, "Characterization and manipulation of the pathway-specific late regulator AlpW reveals Streptomyces ambofaciens as a new producer of Kinamycins", J. Bacteriol, 193, pp.1142~1153 (2011)
  135. Miao V, "Daptomycin biosynthesis in Streptomyces roseosporus : cloning and analysis of the gene cluster and revision of peptide stereochemistry", Microbiology, 151, pp.1507~1523 (2005)
  136. Myronovskyi M, "Iterative marker excision system", Appl. Microbiol. Biotechnol, 98, pp.4557~4570 (2014)
  137. Thapa LP, "Heterologous expression of the kanamycin biosynthetic gene cluster(pSKC2)in Streptomyces venezuelae YJ003", Appl. Microbiol. Biotechnol, 76, pp.1357~1364 (2007)
  138. Jones AC, "Phage p1-derived artificial chromosomes facilitate heterologous expression of the FK506 gene cluster", PLoS One, 8, pp.e69319~ (2013)
  139. Steffensky M, "Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891", Antimicrob. Agents Chemother, 44, pp.1214~1222 (2000)
  140. Zhao Z, "Hybrubins : Bipyrrole tetramic acids obtained by crosstalk between a truncated undecylprodigiosin pathway and heterologous tetramic acid biosynthetic genes", Org. Lett, 18, pp.572~575 (2016)

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