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DAI Yan, WU Xuri, CHEN Yijun. Advances in strategies for activating silent biosynthetic gene clusters in Streptomyces[J]. Journal of China Pharmaceutical University, 2019, 50(4): 379-388. DOI: 10.11665/j.issn.1000-5048.20190401
Citation: DAI Yan, WU Xuri, CHEN Yijun. Advances in strategies for activating silent biosynthetic gene clusters in Streptomyces[J]. Journal of China Pharmaceutical University, 2019, 50(4): 379-388. DOI: 10.11665/j.issn.1000-5048.20190401
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Advances in strategies for activating silent biosynthetic gene clusters in Streptomyces

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  • Microbial secondary metabolites have always been one of the important sources of discovery and development of new drugs due to their remarkable biological activities. The explosion of genome sequences has revealed that Streptomyces harbor an immensely untapped biosynthetic potential. However, the number of active secondary metabolites with new skeletons or structural units found from Streptomyces is much lower than that of biosynthetic gene clusters(BGCs), mainly due to the fact that many BGCs are either expressed weakly or transcriptionally silent under conventional laboratory conditions. Beginning with the bioinformatics tools for BGCs prediction, this review focuses on the classical approaches to activate silent BGCs of Streptomyces in native and heterologous hosts. Moreover, several new strategies including transcriptional factors decoy, reporter-guided high-throughput selection and muliplexed CRISPR-TAR were detailed, which provide methodological references for mining new secondary metabolites from Streptomyces.
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  • [1]
    Baltz RH.Gifted microbes for genome mining and natural product discovery[J].J Ind Microbiol Biotechnol,2016,44(4/5):573-588.
    [2]
    Rutledge PJ,Challis GL.Discovery of microbial natural products by activation of silent biosynthetic gene clusters[J].Nat Rev Microbiol,2015,13(8):509-523.
    [3]
    Yoo YJ,Kim H,Park SR,et al.An overview of rapamycin:from discovery to future perspectives[J].J Ind Microbiol Biotechnol,2017,44(4/5):537-553.
    [4]
    Zarins-Tutt JS,Barberi TT,Gao H,et al.Prospecting for new bacterial metabolites:a glossary of approaches for inducing,activating and upregulating the biosynthesis of bacterial cryptic or silent natural products[J].Nat Prod Rep,2016,33(1):54-72.
    [5]
    Blin K, Kim HU, Medema MH, et al. Recent development of antiSMASH and other computational approaches to mine secondary metabolite biosynthetic gene clusters[J].Brief Bioinformatics,2017.doi: 10.1093/bib/bbx146.
    [6]
    Weber T,Kim HU.The secondary metabolite bioinformatics portal:computational tools to facilitate synthetic biology of secondary metabolite production[J].Synth Syst Biotechnol,2016,1(2):69-79.
    [7]
    Singh M,Chaudhary S,Sareen D.Non-ribosomal peptide synthetases:identifying the cryptic gene clusters and decoding the natural product[J].J Biosci,2017,42(1):175-187.
    [8]
    Röttig M,Medema MH,Blin K,et al.NRPSpredictor2:a web server for predicting NRPS adenylation domain specificity[J].Nucleic Acids Res,2011,39(Web Server issue):W362-W367.
    [9]
    Khater S,Gupta M,Agrawal P,et al.SBSPKSv2:structure-based sequence analysis of polyketide synthases and non-ribosomal peptide synthetases[J].Nucleic Acids Res,2017,45(W1):W72-W79.
    [10]
    Ziemert N,Podell S,Penn K,et al.The natural product domain seeker NaPDoS:a phylogeny based bioinformatic tool to classify secondary metabolite gene diversity[J].PLoS One,2012,7(3):e34064.
    [11]
    Blin K,Wolf T,Chevrette MG,et al.AntiSMASH 4.0—improvements in chemistry prediction and gene cluster boundary identification[J].Nucleic Acids Res,2017,45(W1):W36-W41.
    [12]
    Blin K, Pascal Andreu V, de Los Santos ELC, et al. The antiSMASH database version 2:a comprehensive resource on secondary metabolite biosynthetic gene clusters[J].Nucleic Acids Res,2019,47(D1):D625-D630.
    [13]
    Skinnider MA,Merwin NJ,Johnston CW,et al.PRISM 3:expanded prediction of natural product chemical structures from microbial genomes[J].Nucleic Acids Res,2017,45(W1):W49-W54.
    [14]
    Tietz JI,Schwalen CJ,Patel PS,et al.A new genome-mining tool redefines the lasso peptide biosynthetic landscape[J].Nat Chem Biol,2017,13(5):470-478.
    [15]
    Schwalen CJ,Hudson GA,Bryce K,et al.Bioinformatic expansion and discovery of thiopeptide antibiotics[J].J Am Chem Soc,2018,140(30):9494-9501.
    [16]
    Mohimani H,Kersten RD,Liu WT,et al.Automated genome mining of ribosomal peptide natural products[J].ACS Chem Biol,2014,9(7):1545-1551.
    [17]
    van Heel AJ,de Jong A,Song C,et al.BAGEL4:a user-friendly web server to thoroughly mine RiPPs and bacteriocins[J].Nucleic Acids Res,2018,46(W1):W278-W281.
    [18]
    Agrawal P,Khater S,Gupta M,et al.RiPPMiner:a bioinformatics resource for deciphering chemical structures of RiPPs based on prediction of cleavage and cross-links[J].Nucleic Acids Res,2017,45(W1):W80-W88.
    [19]
    Cimermancic P,Medema MH,Claesen J,et al.Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters[J].Cell,2014,158(2):412-421.
    [20]
    Cruz-Morales P,Kopp JF,Martínez-Guerrero,et al.Phylogenomic analysis of natural products biosynthetic gene clusters allows discovery of arseno-organic metabolites in model Streptomycetes[J].Genome Biol Evol,2016,8(6):1906-1916.
    [21]
    Alanjary M,Kronmiller B,Adamek M,et al.The antibiotic resistant target seeker(ARTS),an exploration engine for antibiotic cluster prioritization and novel drug target discovery[J].Nucleic Acids Res,2017,45(W1):W42-W48.
    [22]
    Bode HB,Bethe B,Höfs R,et al.Big effects from small changes possible ways to explore nature′s chemical diversity[J].Chem Bio Chem,2002,3(7):619-627.
    [23]
    Rateb ME,Houssen WE,Arnold M,et al.Chaxamycins A-D,bioactive ansamycins from a hyper-arid desert Streptomyces sp.[J].J Nat Prod,2011,74(6):1491-1499.
    [24]
    Seyedsayamdost MR.High-throughput platform for the discovery of elicitors of silent bacterial gene clusters[J].Proc Natl Acad Sci U S A,2014,111(20):7266-7271.
    [25]
    Onaka H,Mori Y,Igarashi Y,et al.Mycolic acid-containing bacteria induce natural-product biosynthesis in Streptomyces species[J].Appl Environ Microbiol,2011,77(2):400-406.
    [26]
    Du D,Katsuyama Y,Onaka H,et al.Production of a novel amide-containing polyene by activating a cryptic biosynthetic gene cluster in Streptomyces sp.MSC090213JE08[J].Chem Biol Chem,2016,17(15):1464-1471.
    [27]
    Thanapipatsiri A,Gomez-Escribano JP,Song L,et al.Discovery of unusual biaryl polyketides by activation of a silent Streptomyces venezuelae biosynthetic gene cluster[J].ChemBioChem,2016,17(22):2189-2198.
    [28]
    Wang L,Hu Y,Zhang Y,et al.Role of sgcR3 in positive regulation of enediyne antibiotic C-1027 production of Streptomyces globisporus C-1027[J].BMC Microbiol,2009,9(1):14.
    [29]
    Tong Y,Charusanti P,Zhang L,et al.CRISPR-Cas9 based engineering of actinomycetal genomes[J].ACS Synth Biol,2015,4(9):1020-1029.
    [30]
    Sander JD,Joung JK.CRISPR-Cas systems for editing,regulating and targeting genomes[J].Nat Biotechnol,2014,32(4):347-355.
    [31]
    Tong Y,Robertsen HL,Blin K,et al.CRISPR-Cas9 toolkit for actinomycete genome editing[J].Methods Mol Biol,2018,1671:163-184.
    [32]
    Zhao Y,Li L,Zheng G,et al.CRISPR/dCas9-mediated multiplex gene repression in Streptomyces[J].Biotechnol J,2018,13(9):e1800121.
    [33]
    Mcarthur M,Bibb MJ.Manipulating and understanding antibiotic production in Streptomyces coelicolor A3(2)with decoy oligonucleotides[J].Proc Natl Acad Sci U S A,2008,105(3):1020-1025.
    [34]
    Wang B,Guo F,Dong SH,et al.Activation of silent biosynthetic gene clusters using transcription factor decoys[J].Nat Chem Biol,2019,15(2):111-114.
    [35]
    Zhang MM,Wong FT,Wang Y,et al.CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters[J].Nat Chem Biol,2017,13:607-611.
    [36]
    Ren H,Wang B,Zhao H.Breaking the silence:new strategies for discovering novel natural products[J].Curr Opin Biotechnol,2017,48:21-27.
    [37]
    Xu F,Nazari B,Moon K,et al.Discovery of a cryptic antifungal compound from Streptomyces albus J1074 using high-throughput elicitor screens[J].J Am Chem Soc,2017,139(27):9203-9212.
    [38]
    Guo F,Xiang S,Li L,et al.Targeted activation of silent natural product biosynthesis pathways by reporter-guided mutant selection[J].Metab Eng,2015,28:134-142.
    [39]
    Kim JH,Feng Z,Bauer JD,et al.Cloning large natural product gene clusters from the environment:piecing environmental DNA gene clusters back together with TAR[J].Biopolymers,2010,93(9):833-844.
    [40]
    Lee NCO,Larionov V,Kouprina N.Highly efficient CRISPR/Cas9-mediated TAR cloning of genes and chromosomal loci from complex genomes in yeast[J].Nucleic Acids Res,2015,43(8):e55.
    [41]
    Fu J,Bian X,Hu S,et al.Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting[J].Nat Biotechnol,2012,30(5):440-446.
    [42]
    Li L,Jiang W,Lu Y.New strategies and approaches for engineering biosynthetic gene clusters of microbial natural products[J].Biotechnol Adv,2017,35(8):936-949.
    [43]
    Jiang W,Zhao X,Gabrieli T,et al.Cas9-assisted targeting of chromosome segments CATCH enables one-step targeted cloning of large gene clusters[J].Nat Commun,2015,6:8101.
    [44]
    Du D,Wang L,Tian Y,et al.Genome engineering and direct cloning of antibiotic gene clusters via phage φBT1 integrase-mediated site-specific recombination in Streptomyces[J].Sci Rep,2015,5:8740.
    [45]
    Hu S,Liu Z,Zhang X,et al.“Cre/loxP plus BAC”:a strategy for direct cloning of large DNA fragment and its applications in Photorhabdus luminescens and Agrobacterium tumefaciens[J].Sci Rep,2016,6(1):29087.
    [46]
    Kang HS,Charlop-Powers Z,Brady SF.Multiplexed CRISPR/Cas9 and TAR-mediated promoter engineering of natural product biosynthetic gene clusters in yeast[J].ACS Synth Biol,2016,5(9):1002-1010.
    [47]
    Yamanaka K,Reynolds KA,Kersten RD,et al.Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A[J].Proc Natl Acad Sci U S A,2014,111(5):1957-1962.
    [48]
    Chao R,Yuan Y,Zhao H.Recent advances in DNA assembly technologies[J].FEMS Yeast Res,2015,15(1):1-9.
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