放线菌中与抗生素合成相关TetR家族转录因子的研究进展
|
摘要
放线菌是天然抗生素的重要来源,放线菌中存在着种类繁多的转录因子,精细控制着作为次级代谢产物的抗生素生物合成。作为原核生物单组分信号传递系统中的一个重要家族,TetR家族转录调控因子(TetR family transcriptional regulators,TFRs)广泛参与调控抗生素生物合成、药物外排、初级代谢等多种生理过程。本文综述了近几年放线菌TFRs的研究进展,并结合本实验室的研究工作,从TFRs作用靶基因的角度着重阐述了放线菌TFRs参与几种重要抗生素生物合成的分子调控机制,概述其应答的配体,并总结与展望了放线菌TFRs在抗生素产量提高、沉默基因簇激活、调控元件设计与开发等方面的应用进展。
Actinomycetes are an important source of natural antibiotics, and have a wide variety oftranscription factors that precisely control the biosynthesis of antibiotics as secondary metabolites. As animportant family of prokaryotic single-component signaling systems, TetR family transcriptionalregulators(TFRs) are involved in the regulation of multiple cellular activities such as antibioticbiosynthesis, drug efflux, primary metabolism. On the basis of the recent studies in our lab and theresearch advances published, we review here the molecular regulatory mechanism of TFRs involved in thebiosynthesis of several important antibiotics from the perspective of regulated target genes, and outlinedthe ligands of TFRs. Finally, this review summarizes and indicates the application of TFRs in increasingantibiotic production, activating silent cryptic gene clusters and artificially exploiting synthetic biologyelements.
Actinomycetes are an important source of natural antibiotics, and have a wide variety oftranscription factors that precisely control the biosynthesis of antibiotics as secondary metabolites. As animportant family of prokaryotic single-component signaling systems, TetR family transcriptionalregulators(TFRs) are involved in the regulation of multiple cellular activities such as antibioticbiosynthesis, drug efflux, primary metabolism. On the basis of the recent studies in our lab and theresearch advances published, we review here the molecular regulatory mechanism of TFRs involved in thebiosynthesis of several important antibiotics from the perspective of regulated target genes, and outlinedthe ligands of TFRs. Finally, this review summarizes and indicates the application of TFRs in increasingantibiotic production, activating silent cryptic gene clusters and artificially exploiting synthetic biologyelements.
引文
[1]Lei C,Wang JZ,Liu YY,et al.A feedback regulatory model for RifQ-mediated repression of rifamycin export in Amycolatopsis mediterranei[J].Microbial Cell Factoris,2018,17(1):14
[2]Nett M,Ikeda H,Moore BS.Genomic basis for natural product biosynthetic diversity in the actinomycetes[J].Natural Product Reports,2009,26(11):1362-1384
[3]van der Heul HU,Bilyk BL,McDowall KJ,et al.Regulation of antibiotic production in actinobacteria:new perspectives from the post-genomic era[J].Natural Product Reports,2018,35(6):575-604
[4]Ray S,Maitra A,Biswas A,et al.Functional insights into the mode of DNA and ligand binding of the TetR family regulator TylP from Streptomyces fradiae[J].Journal of Biology Chemistry,2017,292(37):15301-15311
[5]Barbey C,Chane A,Burini JF,et al.A rhodococcal transcriptional regulatory mechanism detects the common lactone ring of AHLquorum-sensing signals and triggers the quorum-quenching response[J].Frontiers in Microbiology,2018,9:2800
[6]He XH,Li H,Pan YY,et al.SCO3129,a TetR family regulator,is responsible for osmotic stress in Streptomyces coelicolor[J].Synthetic and Systems Biotechnology,2018,3(4):261-267
[7]Cuthbertson L,Nodwell JR.The TetR family of regulators[J].Microbiology and Molecular Biology Reviews,2013,77(3):440-475
[8]Oliynyk M,Samborskyy M,Lester JB,et al.Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338[J].Nature Biotechnology,2007,25(4):447-453
[9]Ahn SK,Cuthbertson L,Nodwell JR.Genome context as a predictive tool for identifying regulatory targets of the TetRfamily transcriptional regulators[J].PLoS One,2012,7(11):e50562
[10]Xu YR,Ke ML,Li J,et al.TetR-type regulator SLCG_2919 is a negative regulator of lincomycin biosynthesis in Streptomyces lincolnensis[J].Applied and Environmental Microbiology,2019,85:e02091-18
[11]Wu H,Chen M,Mao YR,et al.Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea[J].Microbial Cell Factories,2014,13:158
[12]Wu H,Wang YS,Yuan L,et al.Inactivation of SACE_3446,a TetR family transcriptional regulator,stimulates erythromycin production in Saccharopolyspora erythraea[J].Synthetic and Systems Biotechnology,2016,1(1):39-46
[13]Wu PP,Pan H,Zhang CM,et al.SACE_3986,a TetR family transcriptional regulator,negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea[J].Journal of Industrial Microbiology&Biotechnology,2014,41(7):1159-1167
[14]Wu H,Chu ZL,Zhang WX,et al.Transcriptome-guided target identification of the TetR-like regulator SACE_5754 and engineered overproduction of erythromycin in Saccharopolyspora erythraea[J].Journal of Biological Engineering,2019,13:11
[15]Xu Z,Wang M,Ye BC.TetR family transcriptional regulator PccD negatively controls propionyl coenzyme A assimilation in Saccharopolyspora erythraea[J].Journal of Bacteriology,2017,199(20):e00281-17
[16]Zhu JY,Chen Z,Li JL,et al.AvaR1,a butenolide-type autoregulator receptor in Streptomyces avermitilis,directly represses avenolide and avermectin biosynthesis and multiple physiological responses[J].Frontiers in Microbiology,2017,8:2577
[17]Zhu JY,Sun D,Liu WS,et al.AvaR2,a pseudoγ-butyrolactone receptor homologue from Streptomyces avermitilis,is a pleiotropic repressor of avermectin and avenolide biosynthesis and cell growth[J].Molecular Microbiology,2016,102(4):562-578
[18]Liu YP,Yan TT,Jiang LB,et al.Characterization of SAV7471,a TetR-family transcriptional regulator involved in the regulation of coenzyme A metabolism in Streptomyces avermitilis[J].Journal of Bacteriology,2013,195(19):4365-4372
[19]He F,Liu WS,Sun D,et al.Engineering of the TetR family transcriptional regulator SAV151 and its target genes increases avermectin production in Streptomyces avermitilis[J].Applied Microbiology and Biotechnology,2014,98(1):399-409
[20]Guo J,Zhang X,Luo S,et al.A novel TetR family transcriptional regulator,SAV576,negatively controls avermectin biosynthesis in Streptomyces avermitilis[J].PLoS One,2013,8(8):e71330
[21]Guo J,Zhang X,Chen Z,et al.Two adjacent and similar TetRfamily transcriptional regulator genes,SAV577 and SAV576,co-regulate avermectin production in Streptomyces avermitilis[J].PLoS One,2014,9(6):e99224
[22]Liu WS,Zhang QL,Guo J,et al.Increasing avermectin production in Streptomyces avermitilis by manipulating the expression of a novel TetR-family regulator and its target gene product[J].Applied and Environmental Microbiology,2015,81(15):5157-5173
[23]Fu JF,Zong GL,Zhang PP,et al.XdhR negatively regulates actinorhodin biosynthesis in Streptomyces coelicolor M145[J].FEMS Microbiology Letters,2017,364(22).DOI:10.1093/femsle/fnx226
[24]Mao XM,Luo S,Zhou RC,et al.Transcriptional regulation of the daptomycin gene cluster in Streptomyces roseosporus by an autoregulator,AtrA[J].The Journal of Biological Chemistry,2015,290(12):7992-8001
[25]Yuan PH,Zhou RC,Chen XP,et al.DepR1,a TetR family transcriptional regulator,positively regulates daptomycin production in an industrial producer,Streptomyces roseosporus SW0702[J].Applied and Environmental Microbiology,2016,82(6):1898-1905
[26]Zhang YY,Pan GH,Zou ZZ,et al.JadR*-mediated feed-forward regulation of cofactor supply in jadomycin biosynthesis[J].Molecular Microbiology,2013,90(4):884-897
[27]Xu GM,Wang J,Wang LQ,et al.“Pseudo”γ-butyrolactone receptors respond to antibiotic signals to coordinate antibiotic biosynthesis[J].The Journal of Biological Chemistry,2010,285(35):27440-27448
[28]Li Y,Li JJ,Tian ZH,et al.Coordinative modulation of chlorothricin biosynthesis by binding of the glycosylated intermediates and end product to a responsive regulator ChlF1[J].The Journal of Biological Chemistry,2016,291(10):5406-5417
[29]Zhao YW,Feng RR,Zheng GS,et al.Involvement of the TetR-type regulator PaaR in the regulation of pristinamycin Ibiosynthesis through an effect on precursor supply in Streptomyces pristinaespiralis[J].Journal of Bacteriology,2015,197(12):2062-2071
[30]Chng C,Lum AM,Vroom JA,et al.A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(32):11346-11351
[31]Wen Y,Zhang LX.Avermectins,intelligently made in China[J].Hereditas(Beijing),2018,40(10):888-899(in Chinese)文莹,张立新.阿维菌素的中国“智”造[J].遗传,2018,40(10):888-899
[32]Betina V.Bioactive Secondary Metabolite of Microorganisms[M].Amsterdam:Elsevier,1994:69
[33]Wu MC,Styles MQ,Law BJC,et al.Engineered biosynthesis of enduracidin lipoglycopeptide antibiotics using the ramoplanin mannosyltransferase Ram29[J].Microbiology,2015,161(7):1338-1347
[34]Zhang BC,Huang XD.Erythromycin drug genetic engineering[J].Biotechnology&Business,2009(1):66-71(in Chinese)张部昌,黄训端.红霉素类药物基因工程[J].生物产业技术,2009(1):66-71
[35]Marsden AF,Caffrey P,Aparicio JF,et al.Stereospecific acyl transfers on the erythromycin-producing polyketide synthase[J].Science,1994,263(5145):378-380
[36]Hopwood DA,Sherman DH.Molecular genetics of polyketides and its comparison to fatty acid biosynthesis[J].Annual Review of Genetics,1990,24:37-62
[37]Xu Z,Liu Y,Ye BC.PccD regulates branched-chain amino acid degradation and exerts a negative effect on erythromycin production in Saccharopolyspora erythraea[J].Applied and Environmental Microbiology,2018,84(8):e00049-18
[38]Liu J,Chen YF,Wang WW,et al.Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea[J].Metabolic Engineering,2017,39:29-37
[39]Chen JS,Liu M,Liu XT,et al.Interrogation of Streptomyces avermitilis for efficient production of avermectins[J].Synthetic and Systems Biotechnology,2016,1(1):7-16
[40]Wu H,Zhang BC,Ma QJ.Advances in Streptomyces autoregulators[J].Chinese Journal of Antibiotics,2007,32(12):712-718(in Chinese)吴杭,张部昌,马清钧.链霉菌自动调控因子的研究进展[J].中国抗生素杂志,2007,32(12):712-718
[41]Wang WX,Zhang JH,Liu X,et al.Identification of a butenolide signaling system that regulates nikkomycin biosynthesis in Streptomyces[J].Journal of Biological Chemistry,2018,293(52):20029-20040
[42]Penzikova GA,Levitov MM,Anisova LN,et al.Formation of streptomycin by an inactive mutant strain of Actinomyces streptomycini under the effect of the stimulating factors[J].Antibiotiki,1971,16(1):27-32
[43]Kitani S,Miyamoto KT,Takamatsu S,et al.Avenolide,a Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis[J].Proceedings of the National Academy of Sciences of the United States of America,2011,108(39):16410-16415
[44]Zhang YY,Zou ZZ,Niu GQ,et al.jadR*and jadR2 act synergistically to repress jadomycin biosynthesis[J].Science China Life Sciences,2013,56(7):584-590
[45]Yang KQ,Han L,Vining LC.Regulation of jadomycin Bproduction in Streptomyces venezuelae ISP5230:involvement of a repressor gene,jadR2[J].Journal of Bacteriology,1995,177(21):6111-6117
[46]Chen L,Chen J,Jiang YQ,et al.Transcriptomics analyses reveal global roles of the regulator AveI in Streptomyces avermitilis[J].FEMS Microbiology Letters,2009,298(2):199-207
[47]Gottelt M,Kol S,Gomez-Escribano JP,et al.Deletion of a regulatory gene within the cpk gene cluster reveals novel antibacterial activity in Streptomyces coelicolor A3(2)[J].Microbiology,2010,156(8):2343-2353
[48]Gomez-Escribano JP,Song LJ,Fox DJ,et al.Structure and biosynthesis of the unusual polyketide alkaloid coelimycin P1,a metabolic product of the cpk gene cluster of Streptomyces coelicolor M145[J].Chemical Science,2012,3(9):2716-2720
[49]Kouprina N,Petrov N,Molina O,et al.Human artificial chromosome with regulated centromere:a tool for genome and cancer studies[J].ACS Synthetic Biology,2018,7(9):1974-1989
[50]Cao JQ,Yao YP,Fan KQ,et al.Harnessing a previously unidentified capability of bacterial allosteric transcription factors for sensing diverse small molecules in vitro[J].Science Advances,2018,4(11):eaau4602
[51]Wu H,Mao YR,Chen M,et al.Capturing the target genes of BldD in Saccharopolyspora erythraea using improved genomic SELEX method[J].Applied Microbiology and Biotechnology,2015,99(6):2683-2692
[52]Munch R,Hiller K,Grote A,et al.Virtual footprint and PRODORIC:an integrative framework for regulon prediction in prokaryotes[J].Bioinformatics,2005,21(22):4187-4189
[2]Nett M,Ikeda H,Moore BS.Genomic basis for natural product biosynthetic diversity in the actinomycetes[J].Natural Product Reports,2009,26(11):1362-1384
[3]van der Heul HU,Bilyk BL,McDowall KJ,et al.Regulation of antibiotic production in actinobacteria:new perspectives from the post-genomic era[J].Natural Product Reports,2018,35(6):575-604
[4]Ray S,Maitra A,Biswas A,et al.Functional insights into the mode of DNA and ligand binding of the TetR family regulator TylP from Streptomyces fradiae[J].Journal of Biology Chemistry,2017,292(37):15301-15311
[5]Barbey C,Chane A,Burini JF,et al.A rhodococcal transcriptional regulatory mechanism detects the common lactone ring of AHLquorum-sensing signals and triggers the quorum-quenching response[J].Frontiers in Microbiology,2018,9:2800
[6]He XH,Li H,Pan YY,et al.SCO3129,a TetR family regulator,is responsible for osmotic stress in Streptomyces coelicolor[J].Synthetic and Systems Biotechnology,2018,3(4):261-267
[7]Cuthbertson L,Nodwell JR.The TetR family of regulators[J].Microbiology and Molecular Biology Reviews,2013,77(3):440-475
[8]Oliynyk M,Samborskyy M,Lester JB,et al.Complete genome sequence of the erythromycin-producing bacterium Saccharopolyspora erythraea NRRL23338[J].Nature Biotechnology,2007,25(4):447-453
[9]Ahn SK,Cuthbertson L,Nodwell JR.Genome context as a predictive tool for identifying regulatory targets of the TetRfamily transcriptional regulators[J].PLoS One,2012,7(11):e50562
[10]Xu YR,Ke ML,Li J,et al.TetR-type regulator SLCG_2919 is a negative regulator of lincomycin biosynthesis in Streptomyces lincolnensis[J].Applied and Environmental Microbiology,2019,85:e02091-18
[11]Wu H,Chen M,Mao YR,et al.Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea[J].Microbial Cell Factories,2014,13:158
[12]Wu H,Wang YS,Yuan L,et al.Inactivation of SACE_3446,a TetR family transcriptional regulator,stimulates erythromycin production in Saccharopolyspora erythraea[J].Synthetic and Systems Biotechnology,2016,1(1):39-46
[13]Wu PP,Pan H,Zhang CM,et al.SACE_3986,a TetR family transcriptional regulator,negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea[J].Journal of Industrial Microbiology&Biotechnology,2014,41(7):1159-1167
[14]Wu H,Chu ZL,Zhang WX,et al.Transcriptome-guided target identification of the TetR-like regulator SACE_5754 and engineered overproduction of erythromycin in Saccharopolyspora erythraea[J].Journal of Biological Engineering,2019,13:11
[15]Xu Z,Wang M,Ye BC.TetR family transcriptional regulator PccD negatively controls propionyl coenzyme A assimilation in Saccharopolyspora erythraea[J].Journal of Bacteriology,2017,199(20):e00281-17
[16]Zhu JY,Chen Z,Li JL,et al.AvaR1,a butenolide-type autoregulator receptor in Streptomyces avermitilis,directly represses avenolide and avermectin biosynthesis and multiple physiological responses[J].Frontiers in Microbiology,2017,8:2577
[17]Zhu JY,Sun D,Liu WS,et al.AvaR2,a pseudoγ-butyrolactone receptor homologue from Streptomyces avermitilis,is a pleiotropic repressor of avermectin and avenolide biosynthesis and cell growth[J].Molecular Microbiology,2016,102(4):562-578
[18]Liu YP,Yan TT,Jiang LB,et al.Characterization of SAV7471,a TetR-family transcriptional regulator involved in the regulation of coenzyme A metabolism in Streptomyces avermitilis[J].Journal of Bacteriology,2013,195(19):4365-4372
[19]He F,Liu WS,Sun D,et al.Engineering of the TetR family transcriptional regulator SAV151 and its target genes increases avermectin production in Streptomyces avermitilis[J].Applied Microbiology and Biotechnology,2014,98(1):399-409
[20]Guo J,Zhang X,Luo S,et al.A novel TetR family transcriptional regulator,SAV576,negatively controls avermectin biosynthesis in Streptomyces avermitilis[J].PLoS One,2013,8(8):e71330
[21]Guo J,Zhang X,Chen Z,et al.Two adjacent and similar TetRfamily transcriptional regulator genes,SAV577 and SAV576,co-regulate avermectin production in Streptomyces avermitilis[J].PLoS One,2014,9(6):e99224
[22]Liu WS,Zhang QL,Guo J,et al.Increasing avermectin production in Streptomyces avermitilis by manipulating the expression of a novel TetR-family regulator and its target gene product[J].Applied and Environmental Microbiology,2015,81(15):5157-5173
[23]Fu JF,Zong GL,Zhang PP,et al.XdhR negatively regulates actinorhodin biosynthesis in Streptomyces coelicolor M145[J].FEMS Microbiology Letters,2017,364(22).DOI:10.1093/femsle/fnx226
[24]Mao XM,Luo S,Zhou RC,et al.Transcriptional regulation of the daptomycin gene cluster in Streptomyces roseosporus by an autoregulator,AtrA[J].The Journal of Biological Chemistry,2015,290(12):7992-8001
[25]Yuan PH,Zhou RC,Chen XP,et al.DepR1,a TetR family transcriptional regulator,positively regulates daptomycin production in an industrial producer,Streptomyces roseosporus SW0702[J].Applied and Environmental Microbiology,2016,82(6):1898-1905
[26]Zhang YY,Pan GH,Zou ZZ,et al.JadR*-mediated feed-forward regulation of cofactor supply in jadomycin biosynthesis[J].Molecular Microbiology,2013,90(4):884-897
[27]Xu GM,Wang J,Wang LQ,et al.“Pseudo”γ-butyrolactone receptors respond to antibiotic signals to coordinate antibiotic biosynthesis[J].The Journal of Biological Chemistry,2010,285(35):27440-27448
[28]Li Y,Li JJ,Tian ZH,et al.Coordinative modulation of chlorothricin biosynthesis by binding of the glycosylated intermediates and end product to a responsive regulator ChlF1[J].The Journal of Biological Chemistry,2016,291(10):5406-5417
[29]Zhao YW,Feng RR,Zheng GS,et al.Involvement of the TetR-type regulator PaaR in the regulation of pristinamycin Ibiosynthesis through an effect on precursor supply in Streptomyces pristinaespiralis[J].Journal of Bacteriology,2015,197(12):2062-2071
[30]Chng C,Lum AM,Vroom JA,et al.A key developmental regulator controls the synthesis of the antibiotic erythromycin in Saccharopolyspora erythraea[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(32):11346-11351
[31]Wen Y,Zhang LX.Avermectins,intelligently made in China[J].Hereditas(Beijing),2018,40(10):888-899(in Chinese)文莹,张立新.阿维菌素的中国“智”造[J].遗传,2018,40(10):888-899
[32]Betina V.Bioactive Secondary Metabolite of Microorganisms[M].Amsterdam:Elsevier,1994:69
[33]Wu MC,Styles MQ,Law BJC,et al.Engineered biosynthesis of enduracidin lipoglycopeptide antibiotics using the ramoplanin mannosyltransferase Ram29[J].Microbiology,2015,161(7):1338-1347
[34]Zhang BC,Huang XD.Erythromycin drug genetic engineering[J].Biotechnology&Business,2009(1):66-71(in Chinese)张部昌,黄训端.红霉素类药物基因工程[J].生物产业技术,2009(1):66-71
[35]Marsden AF,Caffrey P,Aparicio JF,et al.Stereospecific acyl transfers on the erythromycin-producing polyketide synthase[J].Science,1994,263(5145):378-380
[36]Hopwood DA,Sherman DH.Molecular genetics of polyketides and its comparison to fatty acid biosynthesis[J].Annual Review of Genetics,1990,24:37-62
[37]Xu Z,Liu Y,Ye BC.PccD regulates branched-chain amino acid degradation and exerts a negative effect on erythromycin production in Saccharopolyspora erythraea[J].Applied and Environmental Microbiology,2018,84(8):e00049-18
[38]Liu J,Chen YF,Wang WW,et al.Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea[J].Metabolic Engineering,2017,39:29-37
[39]Chen JS,Liu M,Liu XT,et al.Interrogation of Streptomyces avermitilis for efficient production of avermectins[J].Synthetic and Systems Biotechnology,2016,1(1):7-16
[40]Wu H,Zhang BC,Ma QJ.Advances in Streptomyces autoregulators[J].Chinese Journal of Antibiotics,2007,32(12):712-718(in Chinese)吴杭,张部昌,马清钧.链霉菌自动调控因子的研究进展[J].中国抗生素杂志,2007,32(12):712-718
[41]Wang WX,Zhang JH,Liu X,et al.Identification of a butenolide signaling system that regulates nikkomycin biosynthesis in Streptomyces[J].Journal of Biological Chemistry,2018,293(52):20029-20040
[42]Penzikova GA,Levitov MM,Anisova LN,et al.Formation of streptomycin by an inactive mutant strain of Actinomyces streptomycini under the effect of the stimulating factors[J].Antibiotiki,1971,16(1):27-32
[43]Kitani S,Miyamoto KT,Takamatsu S,et al.Avenolide,a Streptomyces hormone controlling antibiotic production in Streptomyces avermitilis[J].Proceedings of the National Academy of Sciences of the United States of America,2011,108(39):16410-16415
[44]Zhang YY,Zou ZZ,Niu GQ,et al.jadR*and jadR2 act synergistically to repress jadomycin biosynthesis[J].Science China Life Sciences,2013,56(7):584-590
[45]Yang KQ,Han L,Vining LC.Regulation of jadomycin Bproduction in Streptomyces venezuelae ISP5230:involvement of a repressor gene,jadR2[J].Journal of Bacteriology,1995,177(21):6111-6117
[46]Chen L,Chen J,Jiang YQ,et al.Transcriptomics analyses reveal global roles of the regulator AveI in Streptomyces avermitilis[J].FEMS Microbiology Letters,2009,298(2):199-207
[47]Gottelt M,Kol S,Gomez-Escribano JP,et al.Deletion of a regulatory gene within the cpk gene cluster reveals novel antibacterial activity in Streptomyces coelicolor A3(2)[J].Microbiology,2010,156(8):2343-2353
[48]Gomez-Escribano JP,Song LJ,Fox DJ,et al.Structure and biosynthesis of the unusual polyketide alkaloid coelimycin P1,a metabolic product of the cpk gene cluster of Streptomyces coelicolor M145[J].Chemical Science,2012,3(9):2716-2720
[49]Kouprina N,Petrov N,Molina O,et al.Human artificial chromosome with regulated centromere:a tool for genome and cancer studies[J].ACS Synthetic Biology,2018,7(9):1974-1989
[50]Cao JQ,Yao YP,Fan KQ,et al.Harnessing a previously unidentified capability of bacterial allosteric transcription factors for sensing diverse small molecules in vitro[J].Science Advances,2018,4(11):eaau4602
[51]Wu H,Mao YR,Chen M,et al.Capturing the target genes of BldD in Saccharopolyspora erythraea using improved genomic SELEX method[J].Applied Microbiology and Biotechnology,2015,99(6):2683-2692
[52]Munch R,Hiller K,Grote A,et al.Virtual footprint and PRODORIC:an integrative framework for regulon prediction in prokaryotes[J].Bioinformatics,2005,21(22):4187-4189