摘要
放线菌(actinomycetes)属于革兰氏阳性细菌中的高G＋C％类群，具有复杂的发育和分化生长周期，产生大约8700种抗生素和生理活性物质，并拥有独特的遗传特征，是微生物领域基础和应用研究的一个重要材料。本文以重要应用价值的除虫链霉菌(Streptomyces avermitilis)和尤马马杜拉放线菌(Actinomadura yumaensis)、模式链霉菌—天蓝色链霉菌(Streptomyces coelicolor)、有独特染色体外遗传因子的链霉菌44414和诺卡氏菌(Nocardia)107等为材料，开展了功能基因组、抗生素生物合成和DNA复制等方面的研究。具体结果包括：
1有序排列的S. avermtitilis基因组文库的构建及多拉菌素(Doramectin)基因工程菌株的获得。以柯斯质粒SuperCos1为载体，构建了除虫链霉菌的基因组文库。对约1000个柯斯质粒上插入片段的两端进行测序，并利用全基因组序列的信息，构建了覆盖约91％基因组的有序排列的柯斯文库。利用λRED高效DNA重组和大肠杆菌-链霉菌接合转移技术，建立了除虫链霉菌的基因组遗传操作系统。可以在该菌中进行高效、精确的基因或基因簇的敲除工作，还能够进行连续的基因缺失研究。运用该系统对几个除虫链霉菌工业生产菌株的次生代谢途径和代谢流向进行了改良，首次获得了遗传改造的可以产生多拉菌素的基因工程菌株。此外，发现aveD和aveF之间可能存在一个前人忽视的基因，发现aveC基因可能直接参与Avermectin的生物合成。
2利用抗生素生物合成正调控基因改造Avermectin和Doramectin的工业生产菌。通过将在模式链霉菌中发现的afsR、aveR、orfX、afsB、cprB、metK等调控基因导入到S. avermtitilis的产生Avermectin工业菌株和Doramectin的突变菌株，发现3种调控基因afsR，aveR和orfX对菌株MMR630阿维菌素的产量均可以提高约1倍。但是，以上的3种，加上另外3种调控基因，分别导入菌株G11后，发现除afsB提高约13％外，其余调控基因使菌株多拉菌素的产量反而有不同程度的降低。将调控基因afsB置于链霉菌强启动子permE~*下表达降低了菌株G11中多拉菌素的含量。这些结果表明，调控基因对于不同链霉菌的抗生素生物合成具有不同的影响，反映了抗生素生物合成确实受到了复杂网络的调控。
3利用新型载体构建基因组文库以进行DNA大片段的敲除。为了对链霉菌基因组进行DNA大片段的敲除，构建了新型的柯斯载体pHAQ31。利用该载体构建了S. avermitilis和S. coelicolor的有序排列的基因组文库，覆盖率分别为73％和62％。利用这二个文库除了可以进行精确的λRED介导的基因替换敲除外，还可以进行DNA大片段的敲除。在S. avermitilis中，利用该系统不带抗性标记，敲除30kb片段的效率可达10％以上。利用该体系尝试了S. coelicolor多个染色体大片段敲除。利用pHAQ31和SuperCos1构建的两套S. avermtitilis基因组文库，构建了敲除S.avermtitilis的除Avermectin合成以外9个聚酮类抗生素生物合成基因簇载体，并完成了部分8基因簇的敲除工作。
4马杜拉霉素(Maduramicin)生物合成基因簇中聚酮合成相关基因片段的克隆。以pHZ1358为载体构建了马杜拉霉素产生菌A. yumaensis的基因组文库。利用从该菌中克隆到的内源探针，对基因组文库筛选获得了9个阳性克隆，通过阳性克隆的两端测序分析，发现4个克隆两侧显示出与聚酮合成酶高度同源，推测可能和马杜拉霉素的生物合成相关。
5链霉菌温度敏感性线型质粒pRL4的复制功能研究。链霉菌44414携带3个内源线型质粒，在40度培养条件下，其中pRL4质粒发生丢失(温度敏感性)。通过部分酶切和克隆鉴定了pRL4的基本复制区域，由一个与S. avermtilis中线型质粒SAP1相似的新的基因和一段非编码区组成。通过比较鉴定了S.avermtilis中线型质粒SAP1的中心基本复制区。
6诺卡氏菌环型质粒pXT107的复制研究。在Nocardia sp. 107中发现质粒pXT107是诺卡氏菌属中报道的最小的环型质粒之一，由4335bp组成。序列分析及功能研究显示，该质粒具有典型的滚环复制质粒的特征。构建的大肠杆菌—诺卡氏菌穿梭质粒pHAQ22能够在N. corallina 4.1037中复制，但不能在变青链霉菌(S.lividans)中复制。
7 A. yumaensis染色体基本复制区的克隆及分析。利用根据dnaA和dnaN保守序列设计的简并引物在马杜拉放线菌中扩增到1.3kb片段。研究发现，尤马马杜拉放线菌染色体复制区位于保守基因dnaA与dnaN之间，包含919碱基对。与已发表的3个属的放线菌染色体oriC序列的特征不同，尤马马杜拉放线菌的染色体oriC含有14个DnaA盒子和2个AT富含区，DnaA盒子的保守序列是(T／C)(T／C)GTCC(A／C)CA。携带该oriC片段的大肠杆菌质粒可以在天蓝色链霉菌中复制和以低拷贝方式遗传。比较来自放线菌4个属的oriC，发现以oriC序列和以16S rDNA序列构建的进化树十分相似，进一步支持了前人的推测。
The actinomycetes, filamentous bacteria belong to high G+C content gram-positive group, have a complex morphological development and differentiation life cycle with unique genetics characters. And produce more than 8700 kinds of antibiotics and physiological activity chemical. So actinomycetes were taken as important materials in fundermental and application research on microorganism. In this thesis, investigation on functional genome, antibiotic biosynthesis and DNA replication were carried out on Streptomyces avermililis and Actinomadura yumaensis (with high commercial values), Streptomyces coelicolor (the model actinomycetes), Streptomyces. sp.44414 and Nocardia sp.107. The results are following:
1 The construction of an ordered genomic library of S. avermitilis and obtainment the genetic-engineering strain to produce Doramectin. A genomic library of S. avermitilis was constructed with the cosmid vector SuperCosl. After sequenced the. both ends of 1000 cosmid clones, an ordered cosmids library covered more than 91% chromosome of S. avermitilis was obtained on the basis of its genome sequence. Base on the cosmids library, a genetic manipulation system were established through theλRED mediated recombination and Escherichia coli-Streptomyces intergeneric conjugative transfer technique. Efficient and precised gene or gene cluster knockout and sequential gene knockout can be carried on in S. avermitilis with this system. An unprecedented genetic modified strain can produced Doramectin was obtained through secondary metabolism engineering and metabolic flux improvement with this system. In addition, a previous overlooked gene between aveD and aveF genes was discovered, aveC might involve in the biosynthesis of Avermectin.
2 Genetic modification of industrial strains of Avermectin-and Doramectin-producers by using positive regulatory genes. Here we reported that several known regulatory genes, afsR, aveR, orfX, afsB, cprB and metK, were cloned into an integrative vector and introduced by conjugal transfer from E. coli to the Streptomyces avermitilis industrial stains that produced Avermectins or Doramectin. The Avermectin Bla yield in strain MMR630 increased about one fold after introduced individually the regulatory genes aveR, afsR or orfX. But strain G11 with the introduced individual 6 genes, including the former three genes, decreased the yield of Doramectin except the afsB gene increased 13%. Expression of afsB gene under the constitutive promoter permE~* decreased the productivity of Doramectin in strain G11. These results indicate that the regulatory genes have differential effects on the antibiotic production of different industrial strains, and suggest that regulatory of antibiotic biosynthesis indeed involves in a complicated network in Streptomyces.
3. Establishment large chromosome fragment deletion on the basis of genomic library constructed with novel cosmid vector. Cosmid vector pHAQ31 was constructed to carry out large DNA fragment deletion research. Ordered cosmids library of S. coelicolor and S. avermtilis constructed with the conjugative cosmids vector pHAQ31 covered each genome 73% and 62% respectively. Both libraries can carry out large fragment deletion besides theλRED mediated gene PCR-targeting system. For example, 30kb fragment no-marker deletion efficiency is more than 10% with this system in S. avermitilis. Large chromosome fragment longer than 80kb deletion were also test in S. coelicolor. Nine vectors were constructed to delete 9 ploketide biosynthetic gene clusters except that of Avermectin used both librarys of S. avermitilis constructed with SuperCos1 and pHAQ31. Now complete the deletion of seven PKS clusters.
4 Cloned DNA fragments related with the biosynthetic gene cluster of Maduramicin. A cosmids genomic library of A. yumaensis NRRL12515 constructed with cosmid vector pHZ1358. Nine positive clones were obtained through screened the library by in situ colony hybridization with the endogenious (3-keto-synthase gene fragment probe,which was amplified with designed degenerate primers on conserved motif in this strain. After both ends seuqnecing, the ends of four clone showed high homologous with PKS genes. It canbe concluded that these 4 clones probably related with the biosynthesis of Maduramicin.
5 Replication of a temperature-sensitive linear plasmid pRL4. Streptomyces sp. 44414 harbored three linear plasmids, and one of them was lost during culturing at 40℃(temperature-sensitive). By partially digested plasmid DNA, cloned into an E. coli plasmid pQC156 and introduced by transformation into Streptomyces lividans ZX7, a replication origin of pRL4, consisting of a linear plasmid SAP1-like gene and a non-coding sequence, was identified. As expected, the SAP1 gene and adjacent non-coding sequence also contained activity of replication.
6 Studies on the Nocardia circular plasmid pXT107. We report here a new identified plasmid pXT107 of Nocardia sp.107, one of the smallest circular plasmid found in Nocardia. The complete nucleotide sequence of pXT107 consisted of 4335-bp with 65% G+C content, encoding one Rep (replication protein) and six proteins of unknown functions. The Rep, double strand origin (dso) and single strand origin (sso) of pXT107 resembled these of typical rolling-circle-replication plasmids, such as pNI100 of Nocardia, pRE8424 of Rhodococcus and pIJ101 of Streptomyces. An E. coli-Nocardia shutter plasmid pHAQ22, containing the rep gene, propagated in Nocardia but not in Streptomyces.
7 Cloning and functional studies of the chromosomal replication origin(oriC) of Actinomadura yumaensis. A 1.3kb fragment amplified in A. yumaensis with degenerate primers designed on the conserved motifs of dnaA and dnaN. Result showed that the oriC was located between the conserved genes dnaA and dnaN of chromosome and consisted of 919 bp. Unlike previous published actinomycetes oriC, the oriC of Actinomadura yumaensis contained 14 DnaA-boxes with conserved 9-bp sequence (T/C)(T/C)GTCC(A/C)CA and 2 AT-rich sequences. An E. coli plasmid carrying the oriC fragment was able to propagate in Streptomyces coelicolor in a low copy number. Phylogenetic trees based on the oriC sequences of four genera actinomycetes and of 16S rDNA were similar, supporting the previous hypothesis.
引文
王茜．链霉菌分化负调节基因nsdA在抗生素高产育种上的应用．[硕士学位论文]．武汉：华中农业大学图书馆，2004
王以光(译)．Lancini G，Parenti F，Gallo GG．抗生素-多学科研究入门．北京：人民卫生出版社，1998
田永强．1稀有放线菌体内遗传因子的生物学研究2链霉菌DNA大片段遗传操作系统的初步建立．[博士学位论文]．上海：中国科学院上海生命科学图书馆，2005
卢捷，马伟，茅翔，覃重军，姜卫红，焦瑞身．除虫链霉菌复制起始区克隆和功能初步分析．生物化学与生物物理学报，2002，34：712-718
刘志恒，姜成林．放线菌现代生物学与生物技术．北京：科学出版社，2004
阮继生等．放线菌研究及应用 北京：科学出版社，1990
朱浩君，梁运祥，周俊初，郑应华．阿维链霉菌bkdF的基因中断对阿维菌素合成的影响．微生物学报， 2004，44：194-197
许铭翾．变铅青链霉菌66内源质粒SLP2和SLP3的研究．[博士学位论文]．上海：中国科学院上海生命科学图书馆，2004
陈芝，文莹，宋渊，，李季伦．阿维链霉菌中aveD基因缺失对阿维菌素合成的影响．微生物学报，2002，42：534-538
吴霞，张一宾．防治畜类寄生线虫的又一阿维菌素类化合物——道拉菌素．农药，2003，42：45-47
张亮．除虫链霉菌(Streptomyces avermitilis)的基因工程改造[硕士学位论文]．上海：中国科学院上海生命科学图书馆，2005
姜成林，徐丽华，许宗雄．放线菌分类学．昆明：云南大学出版社，1995
顾觉奋．应用基因工程改进抗生素产量的研究进展．国外医药．抗生素分册，1999，20：193-197
陶美凤，应新，王茜，李文成，余贞，邓子新，周秀芬．用于提高链霉菌抗生素产量的方法及菌株．中国专利，1831134，2005
徐汉虹，梁明龙，，胡林．阿维菌素类药物的研究进展．华南农业大学学报，2005，26：1-6．
焦瑞身．新世纪微生物学者的一项重要任务——未培养微生物的分离培养．生物工程学报，2004，20：641-645
龚巍．GL—7ACA酰化酶工程菌的分批补料发酵条件优化除虫链霉菌MMR630 AVM B O-甲基转移酶基因的中断和置换．[博士学位论文]．上海：中国科学院上海生命科学图书馆，2002
Baltz R H. Gene expression in recombinant Streptomyces. Bioprocess Technol, 1995, 22: 309-381
Baltz R H, McHenney M A, Cantwell C A, Queener S W, Solenberg P J. Applications of transposition mutagenesis in antibiotic producing Streptomycetes. Antonie Van Leeuwenhoek, 1997, 71: 179-187
Bao K, Cohen S N. Terminal proteins essential for the replication of linear plasmids and chromosomes in Streptomyces. Genes Dev, 2001, 15: 1518-1527
Behki R, Topp E, Dick W, Germon P. Metabolism of the herbicide atrazine by Rhodococcus strains. Appl Environ Microbiol, 1993, 59: 1955-1959
Bentley S D, Chater K F, Cerdeno-Tarraga A M, Challis G L, Thomson N R, James K D, Harris D E, Quail M A, Kieser H, Harper D, Bateman A, Brown S, Chandra G., Chen C W, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, et al. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature, 2002, 417: 141-147
Bevitt D J, Cortes J, Haydock S F, Leadlay P F. 6-Deoxyerythronolide-B synthase 2 from Saccharopolyspora erythraea. Cloning of the structural gene, sequence analysis and inferred domain structure of the multifunctional enzyme. Eur J Biochem, 1992, 204: 39-49
Bibb M. 1995 Colworth Prize Lecture: The regulation of antibiotic production in Streptomyces coelicolor A3(2). Microbiology, 1996, 142: 1335-1344
Bibb M J. Regulation of secondary metabolism in Streptomycetes. Curr Opin Microbiol, 2005, 8: 208-215
Bishop A, Fielding S, Dyson P, Herron P. Systematic insertional mutagenesis of a Streptomycete genome: a link between osmoadaptation and antibiotic production. Genome Res, 2004, 14: 893-900
Borell C W, Stutzman-Engwall K, Wang Y, Otten S L, Donovan M J, Hutchinson C R. Expression of (latent) Streptomyces antibiotic production genes in heterologous hosts: a possibleway to discover new antibiotics. BioTechnology, 1989
Borodina I, Krabben P, Nielsen J. Genome-scale analysis of Streptomyces coelicolor A3(2) metabolism. Genome Res, 2005, 15: 820-829
Bruand C, Le Chatelier E, Ehrlich S D, Janniere L. A fourth class of theta-replicating plasmids: the pAM beta 1 family from gram-positive bacteria. Proc Natl Acad Sci USA, 1993, 90: 11668-11672
Brunker P, Minas W, Kallio P T, Bailey, J. E. Genetic engineering of an industrial strain of Saccharopolyspora erythraea for stable expression of the Vitreoscilla haemoglobin gene (vhb). Microbiology, 1998, 144: 2441-2448
Burg R W, Miller B M, Baker E E, Birnbaum J, Currie S A, Hartman R, Kong Y L, Monaghan R L, Olson G, Putter I, Tunac J B, Wallick H, Stapley EO, Oiwa R, Omura S. Avermectins, new family of potent anthelmintic agents: producing organism and fermentation. Antimicrob Agents Chemother, 1979,15: 361-367
Campbell W C, Fisher M H, Stapley EO, Albers-Schonberg G, Jacob T A. Ivermectin: a potent new antiparasitic agent. Science, 1983,221: 823-828
Cane D, Liangm T, Kaplan L, Nallin M, Schulman M, Hensens O, Douglas A, Albers-Schonberg G. Biosynthetic origin of the carbon skeleton and oxygen atoms of the avermectins. J Am Chem Soc, 1983,105: 4110-4112
Cane D E, Walsh C T, Khosla C. Harnessing the biosynthetic code: combinations, permutations, and mutations. Science, 1998,282: 63-68
Chakraburtty R, White J, Takano E, Bibb, M. Cloning, characterization and disruption of a (p)ppGpp synthetase gene (relA) of Streptomyces coelicolor A3(2). Mol Microbiol, 1996,19: 357-368
Chang P C, Cohen S N. Bidirectional replication from an internal origin in a linear streptomyces plasmid. Science, 1994, 265: 952-954
Chang P C, Kim E S, Cohen SN. Streptomyces linear plasmids that contain a phage-like, centrally located, replication origin. Mol Microbiol ,1996, 22: 789-800.
Chater K, Bibb M, Bruton C, Hop wood D, Janssen G, Malpartida F, Smith C. Dissecting the Streptomyces genome. Biochem Soc Trans, 1984, 12: 584-586
Chater K F. The improving prospects for yield increase by genetic engineering in antibiotic-producing Streptomycetes. Biotechnology, 1990, 8: 115-121
Chen C W, Yu T W, Lin Y S, Kieser H M, Hopwood D A. The conjugative plasmid SLP2 of Streptomyces lividans is a 50 kb linear molecule. Mol Microbiol, 1993, 7: 925-932
Combes P, Till R, Bee S, Smith M C. The streptomyces genome contains multiple pseudo-attB sites for the (phi)C31-encoded site-specific recombination system. J Bacteriol, 2002,184: 5746-5752
Cowan D, Meyer Q, Stafford W, Muyanga S, Cameron R, Wittwer, P. Metagenomic gene discovery: past, present and future. Trends Biotechnol, 2005, 23: 321-329
Crameri R, and Davies J E. Increased production of aminoglycosides associated with amplified antibiotic resistance genes. J Antibiot, 1986, 39: 128-135
Datsenko K A, Wanner B L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA, 2000, 97: 6640-6645
Denis-Larose C, Labbe D, Bergeron H, Jones A M, Greer C W, al-Hawari J, Grossman M J, Sankey B M, Lau P C. Conservation of plasmid-encoded dibenzothiophene desulfurization genes in several rhodococci. Appl Environ Microbiol, 1997, 63: 2915-2919
Denoya C D, Fedechko R W, Hafner E W, McArthur H A, Morgenstern M R, Skinner D D, Stutzman-Engwall K, Wax R G, Wernau W C. A second branched-chain alpha-keto acid dehydrogenase gene cluster (bkdFGH) from Streptomyces avermitilis: its relationship to avermectin biosynthesis and the construction of a bkdF mutant suitable for the production of novel antiparasitic avermectins. J Bacteriol ,1995,177: 3504-3511
Dutton C J, Gibson S P, Goudie A C, Holdom K S, Pacey M S, Ruddock J C, Bu'Lock J D, Richards M K. Novel avermectins produced by mutational biosynthesis. J Antibiot, 1991, 44: 357-365
Egerton J R, Ostlind D A, Blair L S, Eary C H, Suhayda D, Cifelli S, Riek R F, Campbell W C. Avermectins, new family of potent anthelmintic agents: efficacy of the Bla component. Antimicrob Agents Chemother, 1979,15: 372-378
Espinosa M, del Solar G, Rojo F, Alonso J C. Plasmid rolling circle replication and its control. FEMS Microbiol Lett, 1995,130: 111-120
Eustaquio A S, Gust B, Li S M, Pelzer S, Wohlleben W, Chater K F, Heide L. Production of 8'-halogenated and 8'-unsubstituted novobiocin derivatives in genetically engineered Streptomyces coelicolor strains. Chem Biol, 2004,11: 1561-1572
Fernandez-Gonzalez C, Cadenas R F, Noirot-Gros M F, Martin J F, Gil JA. Characterization of a region of plasmid pBL1 of Brevibacterium lactofermentum involved in replication via the rolling circle model. J Bacteriol, 1994, 176: 3154-3161
Fleck W F, Strauss D G, Meyer J, Porstendorfer G. Fermentation, isolation, and biological activity of maduramycin: a new antibiotic from Actinomadura rubra. Z Allg Mikrobiol, 1978,18: 389-398
Fleck W F, Schlegel B, Ihn W. New anthracycline antibiotics produced by interspecific recombinants of streptomycetes. IV. Antimicrobial activity of iremycin. Z Allg Mikrobiol, 1982,22:349-353
Flett F, Mersinias V, Smith C P. High efficiency intergeneric conjugal transfer of plasmid DNA from Escherichia coli to methyl DNA-restricting streptomycetes. FEMS Microbiol Lett, 1997,155: 223-229
Floriano B, Bibb M. afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3 (2). Mol Microbiol, 1996, 21: 385-396
Fox G E, Stackebrandt E, Hespell R B, Gibson J, Maniloff J, Dyer T A, Wolfe R S, Balch W E, Tanner R S, Magrum L J, Zablen L B, Blakemore R, Gupta R, Bonen L, Lewis B J, Stahl D A, Luehrsen K R, Chen K N, Woese CR. The phylogeny of prokaryotes. Science, 1980, 209: 457-463
Fujii T, Gramajo H C, Takano E, Bibb M J. redD and actII-ORF4, pathway-specific regulatory genes for antibiotic production in Streptomyces coelicolor A3 (2), are transcribed in vitro by an RNA polymerase holoenzyme containing sigma hrdD. J Bacteriol, 1996,178: 3402-3405
Fujikawa N, Kurumizaka H, Nureki O, Terada T, Shirouzu M, Katayama T, Yokoyama S. Structural basis of replication origin recognition by the DnaA protein. Nucleic Acids Res, 2003,31: 2077-2086
Gaisser S, Kellenberger L, Kaja A L, Weston A J, Lill R E, Wirtz G, Kendrew S G, Low L, Sheridan R M, Wilkinson B, Galloway I S, Stutzman-Engwall K, McArthur H A, Staunton J, Leadlay P F. Direct production of ivermectin-like drugs after domain exchange in the avermectin polyketide synthase of Streptomyces avermitilis ATCC31272. Org Biomol Chem, 2003,1: 2840-2847
Ginolhac A, Jarrin C, Gillet B, Robe P, Pujic P, Tuphile K, Bertrand H, Vogel T M, Perriere G, Simonet P, Nalin R. Phylogenetic analysis of polyketide synthase I domains from soil metagenomic libraries allows selection of promising clones. Appl Environ Microbiol, 2004, 70: 5522-5527
Gravius B, Glocker D, Pigac J, Pandza K, Hranueli D, Cullum J. The 387 kb linear plasmid pPZG101 of Streptomyces rimosus and its interactions with the chromosome. Microbiology, 1994,140: 2271-2277
Gust B, Challis G L, Fowler K, Kieser T, Chater, K F. PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc Natl Acad Sci USA, 2003,100: 1541-1546
Gust B, Chandra G, Jakimowicz D, Yuqing T, Bruton C J, Chater K F. Lambda red-mediated genetic manipulation of antibiotic-producing Streptomyces. Adv Appl Microbiol, 2004, 54: 107-128
Hafner E W, Holley B W, Holdom K S, Lee S E, Wax R G, Beck D, McArthur H A, Wernau WC. Branched-chain fatty acid requirement for avermectin production by a mutant of Streptomyces avermitilis lacking branched-chain 2-oxo acid dehydrogenase activity. J Antibiot, 1991, 44: 349-356
Haug I, Weissenborn A, Brolle D, Bentley S, Kieser T, Altenbuchner J. Streptomyces coelicolor A3(2) plasmid SCP2: deductions from the complete sequence. Microbiology, 2003, 149: 505-513
Hayakawa T, Otake N, Yonehara H, Tanaka T, Sakaguchi K. Isolation and characterization of plasmids from Streptomyces. J Antibiot, 1979, 32: 1348-1350
Hesketh A, Ochi K. A novel method for improving Streptomyces coelicolor A3(2) for production of actinorhodin by introduction of rpsL (encoding ribosomal protein S12) mutations conferring resistance to streptomycin. J Antibiot, 1997, 50: 532-535.
Hiratsu K, Mochizuki S, Kinashi H. Cloning and analysis of the replication origin and the telomeres of the large linear plasmid pSLA2-L in Streptomyces rochei. Mol Gen Genet, 2000, 263: 1015-1021
Hong Y S, Lee J H, Kim H S, Kim K W, Lee J J. Targeted gene disruption of the avermectin B O-methyltransferase gene in Streptomyces avermitilis. Biotechnology Letters, 2001, 23: 1765-1770
Hopwood D A, Wright H M. CDA is a new chromosomally-determined antibiotic from Streptomyces coelicolor A3(2). J Gen Microbiol, 1983, 129: 3575-3579
Hopwood D A, Kieser T, Lydiate D J, Bibb M J. In: Antibiotic-Producing Streptomyces, vol.9 of The Bacteria, Queener, S W, Day L E., eds., Newyork: NY Academic, 1986.159-230
Horinouchi S, Malpartida F, Hopwood D A, Beppu T. afsB stimulates transcription of the actinorhodin biosynthetic pathway in Streptomyces coelicolor A3(2) and Streptomyces lividans. Mol Gen Genet, 1989, 215: 355-357
Hotson I K. The avermectins: A new family of antiparasitic agents. J S Afr Vet Assoc, 1982, 53: 87-90
Hu H, Ochi K. Novel approach for improving the productivity of antibiotic-producing strains by inducing combined resistant mutations. Appl Environ Microbiol, 2001, 67: 1885-1892
Huang C H, Chen C Y, Tsai H H, Chen C, Lin Y S, Chen C W. Linear plasmid SLP2 of Streptomyces lividans is a composite replicon. Mol Microbiol, 2003, 47: 1563-1576
Huang C H, Lin Y S, Yang Y L, Huang S W, Chen C W. The telomeres of Streptomyces chromosomes contain conserved palindromic sequences with potential to form complex secondary structures. Mol Microbiol, 1998, 28: 905-916
Huang J, Shi J, Molle V, Sohlberg B, Weaver D, Bibb M J, Karoonuthaisiri N, Lih C J,
Kao C M, Buttner M J, Cohen SN. Cross-regulation among disparate antibiotic biosynthetic pathways of Streptomyces coelicolor. Mol Microbiol, 2005, 58: 1276-1287
Hwang Y S, Kim E S, Biro S, Choi CY. Cloning and analysis of a DNA fragment stimulating avermectin production in various Streptomyces avermitilis strains. Appl Environ Microbiol, 2003,69: 1263-1269
Ikeda H, Omura S. Control of avermectin biosynthesis in Streptomyces avermitilis for the selective production of a useful component. J Antibiot, 1995,48: 549-562
Ikeda H, Pang C H, Endo H, Ohta T, Tanaka H, Omura S. Construction of a single component producer from the wild type avermectin producer Streptomyces avermitilis. JAntibiot, 1995, 48: 532-534
Ikeda H, Omura S. Avermectin Biosynthesis. Chem Rev, 1997, 97: 2591-2610
Ikeda H, Nonomiya T, Usami M, Ohta T, Omura S. Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis. Proc Natl Acad Sci USA, 1999, 96: 9509-9514
Ikeda H. Genetic analysis of biosynthesis of polyketide compound in Streptomyces avermitilis. Jpn J Antibiot, 2001, 54: 112-116
Ikeda H, Nonomiya T, Omura S. Organization of biosynthetic gene cluster for avermectin in Streptomyces avermitilis: analysis of enzymatic domains in four polyketide synthases. J Ind Microbiol Biotechnol, 2001,27: 170-176
Ikeda H, Ishikawa J, Hanamoto A, Shinose M, Kikuchi H, Shiba T, Sakaki Y, Hattori M, Omura S. Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nat Biotechnol, 2003, 21: 526-531
Ilyina TV K E. Conserved sequence motifs in the initiator proteins for rolling circle DNA replication encoded by diverse replicons from eubacteria, eucaryotes and archaebacteria. Nucleic Acids Res, 1992, 20: 3279-3285
Ishikawa J, Hotta K. FramePlot: a new implementation of the frame analysis for predicting protein-coding regions in bacterial DNA with a high G + C content. FEMS Microbiol Lett, 1999,174: 251-253
Ishikawa J, Yamashita A, Mikami Y, Hoshino Y, Kurita H, Hotta K, Shiba T, Hattori,M. The complete genomic sequence of Nocardia farcinica IFM 10152. Proc Natl Acad Sci USA, 2004,101: 14925-14930
Izumikawa M, Murata M, Tachibana K, Ebizuka Y, Fujii I. Cloning of modular type I polyketide synthase genes from salinomycin producing strain of Streptomyces albus. Bioorg Med Chem, 2003,11: 3401-3405
Jakimowicz D, Majka J, Messer W, Speck C, Fernandez M, Martin M C, Sanchez J, Schauwecker F, Keller U, Schrempf H, Zakrzewska-Czerwinska J. Structural elements of the Streptomyces oriC region and their interactions with the DnaA protein. Microbiology, 1998, 144: 1281-1290
Jones G H, Hopwood D A. Activation of phenoxazinone synthase expression in Streptomyces lividans by cloned DNA sequences from Streptomyces antibioticus. J Biol Chem, 1984, 259: 14158-14164
Kataoka M, Kiyose Y M, Michisuji Y, Horiguchi T, Seki T, Yoshida T. Complete nucleotide sequence of the Streptomyces nigrifaciens plasmid, pSN22: genetic organization and correlation with genetic properties. Plasmid, 1994a, 32: 55-69
Kataoka M, Kuno N, Horiguchi T, Seki T, Yoshida T. Replication of the Streptomyces plasmid pSN22 through single-stranded intermediates. Mol Gen Genet, 1994b, 242: 130-136
Katz E, Thompson C J, Hopwood DA. Cloning and expression of the tyrosinase gene from Streptomyces antibioticus in Streptomyces lividans. J Gen Microbiol, 1983, 129: 2703-2714
Keatinge-Clay AT, Shelat A A, Savage D F, Tsai S C, Miercke L J, O'Connell J D, Khosla C, Stroud R M. Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA: ACP transacylase. Structure (Camb), 2003, 11: 147-154
Kendall K J, Cohen S N. Complete nucleotide sequence of the Streptomyces lividans plasmid pIJ101 and correlation of the sequence with genetic properties. J Bacteriol, 1988, 170: 4634-4651
Khan S A. Plasmid rolling-circle replication: recent developments. Mol Microbiol, 2000, 37: 477-484
Khan S A. Plasmid rolling-circle replication: highlights of two decades of research. Plasmid, 2005, 53: 126-136
Kieser T, Bibb M, Buttner M, Chater K F, Hopwood D A. Practical Streptomyces Genetics Norwich, UK: The John Innes Foundation, 2000
Kinashi H, Shimaji M, Sakai A. Giant linear plasmids in Streptomyces which code for antibiotic biosynthesis genes. Nature, 1987, 328: 454-456
Kramer M G, Espinosa M, Misra T K, Khan S A. Characterization of a single-strand origin, ssoU, required for broad host range replication of rolling-circle plasmids. Mol Microbiol, 1999, 33: 466-475
Krishna P S, Venkateswarlu G, Pandey A, Rao L V. Biosynthesis of rifamycin SV by Amycolatopsis mediterranei MTCC 17 in solid cultures. Biotechnol Appl Biochem, 2003,37:311-315
Kues U, Stahl U. Replication of plasmids in gram-negative bacteria. Microbiol Rev, 1989, 53:491-516
Lautru S, Deeth RJ, Bailey LM, Challis G L. Discovery of a new peptide natural product by Streptomyces coelicolor genome mining. Nat Chem Biol, 2005,1: 265-269
Leadlay P F, Staunton J, Oliynyk M, Bisang C, Cortes J, Frost E, Hughes-Thomas ZA, Jones M A, Kendrew S G, Lester J B, Long P F, McArthur H A, McCormick E L, Oliynyk Z, Stark C B, Wilkinson C J. Engineering of complex polyketide biosynthesis—insights from sequencing of the monensin biosynthetic gene cluster. J Ind Microbiol Biotechnol, 2001,27: 360-367
Li Y D, Li Y Q, Chen J S, Dong H J, Guan W J, Zhou H. Whole genome analysis of non-optimal codon usage in secretory signal sequences of Streptomyces coelicolor. Biosystems, 2006, 85: 225-230
Lin X, Hopson R, Cane D E. Genome mining in streptomyces coelicolor: molecular cloning and characterization of a new sesquiterpene synthase. J Am Chem Soc, 2006,128: 6022-6023
Lin Y S, Kieser H M, Hopwood D A, Chen C W. The chromosomal DNA of Streptomyces lividans 66 is linear. Mol Microbiol, 1993,10: 923-933
Liu Y T, Su C M, Lee C H, Sui M J, Chang Y H, Lin W P, Wu W T, Chen C Y. Cloning and characterization of the replicon of the Nocardia italica plasmid, pNI100. Plasmid, 2000, 43: 223-229
Mackiewicz P, Zakrzewska-Czerwinska J, Zawilak A, Dudek M R, Cebrat S. Where does bacterial replication start? Rules for predicting the oriC region. Nucleic Acids Res, 2004,32:3781-3791
Malmberg L H, Hu W S, Sherman D H. Precursor flux control through targeted chromosomal insertion of the lysine epsilon-aminotransferase (lat) gene in cephamycin C biosynthesis. J Bacteriol, 1993,175: 6916-6924
Malpartida F, Hopwood DA. Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host. Nature, 1984, 309: 462-464.
Malpartida F, Hallam S E, Kieser H M, Motamedi H, Hutchinson C R, Butler M J, Sugden D A, Warren M, McKillop C, Bailey C R, et al. Homology between Streptomyces genes coding for synthesis of different polyketides used to clone antibiotic biosynthetic genes. Nature, 1987, 325: 818-821
Mazieres N, Peyre M, Penasse L. Interspecific recombination among aminoglycoside producing streptomycetes. J Antibiot, 1981, 34: 544-550
Mehra S, Lian W, Jayapal K P, Charaniya S P, Sherman D H, Hu W S. A framework to analyze multiple time series data: a case study with Streptomyces coelicolor. J Ind Microbiol Biotechnol, 2006, 33: 159-172
Messer W, Blaesing F, Jakimowicz D, Krause M, Majka J, Nardmann J, Schaper S, Seitz H, Speck C, Weigel C, Wegrzyn G, Welzeck M, Zakrzewska-Czerwinska J. Bacterial replication initiator DnaA. Rules for DnaA binding and roles of DnaA in origin unwinding and helicase loading. Biochimie, 2001, 83: 5-12
Messer W. The bacterial replication initiator DnaA. DnaA and oriC, the bacterial mode to initiate DNA replication. FEMS Microbiol Rev, 2002, 26: 355-374
Metsa-Ketela M, Ylihonko K, Mantsala P. Partial activation of a silent angucycline-type gene cluster from a rubromycin beta producing Streptomyces sp. PGA64. J Antibiot, 2004, 57: 502-510
Mironov V A, Sergienko O V, Nastasiak I N, Danilenko V N. Biogenesis and regulation of biosynthesis of erythromycins in Saccharopolyspora erythraea: a review. Prikl Biokhim Mikrobiol, 2004, 40: 613-624
Mochizuki S, Hiratsu K, Suwa M, Ishii T, Sugino F, Yamada K, Kinashi H. The large linear plasmid pSLA2-L of Streptomyces rochei has an unusually condensed gene organization for secondary metabolism. Mol Microbiol. 2003, 48: 1501-1510
Musialowski M S, Flett F, Scott G B, Hobbs G, Smith C P, Oliver, S G. Functional evidence that the principal DNA replication origin of the Streptomyces coelicolor chromosome is close to the dnaA-gyrB region. J Bacteriol, 1994, 176: 5123-5125
Muyrers J P, Zhang Y, Buchholz F, Stewart A F. RecE/RecT and Redalpha/Redbeta initiate double-stranded break repair by specifically interacting with their respective partners. Genes Dev, 2000, 14: 1971-1982
Nakashima N, Tamura T. Isolation and characterization of a rolling-circle-type plasmid from Rhodococcus erythropolis and application of the plasmid to multiple-recombinant-protein expression. Appl Environ Microbiol, 2004, 70: 5557-5568.
Ochi K, Zhang D, Kawamoto S, Hesketh A. Molecular and functional analysis of the ribosomal L11 and S12 protein genes (rplK and rpsL) of Streptomyces coelicolor A3(2). Mol Gen Genet, 1997, 256: 488-498
Okamoto S, Lezhava A, Hosaka T, Okamoto-Hosoya Y, Ochi K. Enhanced expression of S-adenosylmethionine synthetase causes overproduction of actinorhodin in Streptomyces coelicolor A3(2). J Bacteriol, 2003, 185: 601-609
Oliynyk M, Stark C B, Bhatt A, Jones M A, Hughes-Thomas Z A, Wilkinson C, Oliynyk Z, Demydchuk Y, Staunton J, Leadlay P F. Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization. Mol Micmbiol, 2003,49: 1179-1190
Omura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M, Takahashi Y, Horikawa H, Nakazawa H, Osonoe T, Kikuchi H, Shiba T, Sakaki Y, Hattori M. Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci USA , 2001,98: 12215-12220
Onaka H, Nakagawa T, Horinouchi S. Involvement of two A-factor receptor homologues in Streptomyces coelicolor A3 (2) in the regulation of secondary metabolism and morphogenesis. Mol Microbiol, 1998, 28: 743-753
Pang X, Sun Y, Liu J, Zhou X, Deng Z. A linear plasmid temperature-sensitive for replication in Streptomyces hygroscopicus 10-22. FEMS Microbiol Lett, 2002, 208: 25-28
Pedulla M L, Ford M E, Houtz J M, Karthikeyan T, Wadsworth C, Lewis J A, Jacobs-Sera D, Falbo J, Gross J, Pannunzio N R, Brucker W, Kumar V, Kandasamy J, Keenan L, Bardarov S, Kriakov J, Lawrence J G, Jacobs WR, Jr, Hendrix RW, Hatfull G F. Origins of highly mosaic mycobacteriophage genomes. Cell, 2003,113: 171-182
Qin M H, Madiraju M V, Zachariah S, Rajagopalan M. Characterization of the oriC region of Mycobacterium smegmatis. J Bacteriol, 1997,179: 6311-6317
Qin Z, Cohen S N. Replication at the telomeres of the Streptomyces linear plasmid pSLA2. Mol Microbiol, 1998,28:893-903
Qin Z, Cohen S N. Survival mechanisms for Streptomyces linear replicons after telomere damage. Mol Microbiol, 2002, 45: 785-794
Qin Z, Shen M, Cohen S N. Identification and characterization of a pSLA2 plasmid locus required for linear DNA replication and circular plasmid stable inheritance in Streptomyces lividans. J Bacteriol, 2003,185: 6575-6582
Redenbach M, Bibb M, Gust B, Seitz B, Spychaj A. The linear plasmid SCP1 of Streptomyces coelicolor A3(2) possesses a centrally located replication origin and shows significant homology to the transposon Tn4811. Plasmid, 1999, 42: 174-185
Redenbach M, Kieser H M, Denapaite D, Eichner A, Cullum J, Kinashi H, Hopwood D A. A set of ordered cosmids and a detailed genetic and physical map for the 8 Mb Streptomyces coelicolor A3(2) chromosome. Mo/ Microbiol, 1996,21: 77-96
Redenbach M, Scheel J, Schmidt U. Chromosome topology and genome size of selected actinomycetes species. Antonie Van Leeuwenhoek, 2000, 78: 227-235
Rinehart K L Jr, Cook J C Jr, Meng H, Olson K L, Pandey R C. Mass spectrometric determination of molecular formulas for membrane-modifying antibiotics. Nature, 1977,269:832-833
Ross L, Goff M. Latent tuberculosis infection and BCG vaccination. J Midwifery Womens Health, 2005, 50: 344-347
Rudd B A, Hopwood D A. Genetics of actinorhodin biosynthesis by Streptomyces coelicolor A3(2). J Gen Microbiol, 1979,114: 35-43
Sambrook J, Russell D. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor. NY: Cold Spring Harbor Laboratory Press, 2001
Schirmer A, Gadkari R, Reeves C D, Ibrahim F, DeLong E F, Hutchinson C R. Metagenomic analysis reveals diverse polyketide synthase gene clusters in microorganisms associated with the marine sponge Discodermia dissoluta. Appl Environ Microbiol, 2005, 71: 4840-4849
Schlegel B, Fleck W F. New anthracycline antibiotics produced by interspecific recombinants of streptomycetes-. I. Selection of Streptomyces violaceus subsp. iremyceticus, an iremycin-producing subspecies. Z Allg Mikrobiol, 1980, 20: 527-530
Schlegel B, Ihn W, Fleck W F. (1980) New anthracycline antibiotics produced by interspecific recombinants of streptomycetes. II. Production of iremycin. Z Allg Mikrobiol 20: 531-534
Schulman M D, Valentino D, Hensens O. Biosynthesis of the avermectins by Streptomyces avermitilis. Incorporation of labeled precursors. J Antibiot, 1986, 39: 541-549
Servin-Gonzalez L. Relationship between the replication functions of Streptomyces plasmidspJV1 and pIJ101. Plasmid, 1993,30: 131-140
Servin-Gonzalez L, Sampieri A I, Cabello J, Galvan L, Juarez V, Castro C. Sequence and functional analysis of the Streptomyces phaeochromogenes plasmid pJV1 reveals a modular organization of Streptomyces plasmids that replicate by rolling circle. Microbiology, 1995,141: 2499-2510
Shiffman D, Cohen S N. Reconstruction of a Streptomyces linear replicon from separately cloned DNA fragments: existence of a cryptic origin of circular replication within the linear plasmid. Proc Natl Acad Sci USA, 1992, 89: 6129-6133
Solenberg P J, Cantwell C A, Tietz A J, McGilvray D, Queener S W, Baltz R H. Transposition mutagenesis in Streptomyces fradiae: identification of a neutral site for the stable insertion of DNA by transposon exchange. Gene, 1996,168: 67-72
Stackebrandt E, Ludwig W, Schleifer K H, Gross H J. Rapid cataloging of ribonuclease T1 resistant oligonucleotides from ribosomal RNAs for phylogenetic studies. J Mol Evol, 1981,17:227-236
Stackebrandt E, Woese C R. The phylogeny of prokaryotes. Microbiol Sci, 1984, 1: 117-122
Stassi D, Post D, Satter M, Jackson M, Maine G. A genetically engineered strain of Saccharopolyspora erythraea that produces 6,12-dideoxyerythromycin A as the major fermentation product. Appl Microbiol Biotechnol, 1998, 49: 725-731
Stutzman-Engwall, Kim J P, Brenda S. Streptomyces avermitilis regulatory genes for increased avermectin production. USA Patent, 6197591, 2001
Stutzman-Engwall K, Conlon S, Fedechko R, Kaczmarek F, McArthur H, Krebber A, Chen Y, Minshull J, Raillard S A, Gustafsson C. Engineering the aveC gene to enhance the ratio of doramectin to its CHC-B2 analogue produced in Streptomyces avermitilis. Biotechnol Bioeng, 2003, 82: 359-369
Stutzman-Engwall K, Conlon S, Fedechko R, McArthur H, Pekrun K, Chen Y, Jenne S, La C, Trinh N, Kim S, Zhang Y X, Fox R, Gustafsson C, Krebber A. Semi-synthetic DNA shuffling of aveC leads to improved industrial scale production of doramectin by Streptomyces avermitilis. Metab Eng, 2005, 7: 27-37
Sun Y, Zhou X, Dong H. Tu G, Wang M, Wang B, Den, Z. A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin. Chem Biol, 2003,10: 431-441
Suzuki I, Seki T, Yoshida T. Nucleotide sequence of a nicking site of the Streptomyces plasmid pSN22 replicating by the rolling circle mechanism. FEMS Microbiol Lett, 1997,150:283-288
Tamehiro N, Hosaka T, Xu J, Hu H, Otake N, Ochi K. Innovative approach for improvement of an antibiotic-overproducing industrial strain of Streptomyces albus. Appl Environ Microbiol, 2003, 69: 6412-6417
Thomas D I, Cove J H, Baumberg S, Jones C A, Rudd B A. Plasmid effects on secondary metabolite production by a streptomycete synthesizing an anthelmintic macrolide. J Gen Microbiol, 1991,137: 2331-2337
Tian Y, Hao P, Zhao G, Qin Z. Cloning and characterization of the chromosomal replication origin region of Amycolatopsis mediterranei U32. Biochem Biophys Res Commun, 2005,333: 14-20
Tobias K M, Mark J B, Chater K F, Hopwood D A. Practical Streptomyces Genetics The John Innes Foundation, Norwich, UK, 2000
Tsou H, Rajan S, Fiala R, Mowery P C, Bullock M W, Borders D B, James J C, Martin J H, Morton G O. Biosynthesis of the antibiotic maduramicin. Origin of the carbon and oxygen atoms as well as the 13C NMR assignments. J Antibiot, 1984, 37: 1651-1663
Tsou H R, Rajan S, Chang T T, Fiala R R, Stockton G W, Bullock M W. The utilization of molecular oxygen during the biosynthesis of maduramicin. J Antibiot, 1987, 40: 94-99
van Wageningen A M, Kirkpatrick P N, Williams D H, Harris B R, Kershaw J K, Lennard, N J Jones M, Jones S J, Solenberg P J. Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic. Chem Biol, 1998, 5: 155-162.
Volff J N, Altenbuchner J. Genetic instability of the Streptomyces chromosome. Mol Microbiol, 1998, 27: 239-246
Warwick S, Bowen T, McVeigh H, Embley T M. A phylogenetic analysis of the family Pseudonocardiaceae and the genera Actinokineospora and Saccharothrix with 16S rRNA sequences and a proposal to combine the genera Amycolata and Pseudonocardia in an emended genus Pseudonocardia. Int J Syst Bacteriol, 1994, 44: 293-299.
Weber J M, Leung J O, Swanson S J, Idler K B, McAlpine J B. An erythromycin derivative produced by targeted gene disruption in Saccharopolyspora erythraea. Science, 1991,252:114-117
Weissman K J, Leadlay PF. Combinatorial biosynthesis of reduced polyketides. Nat Rev Microbiol, 2005, 3: 925-936
Weist S, Sussmuth R D. Mutational biosynthesis-a tool for the generation of structural diversity in the biosynthesis of antibiotics. Appl Microbiol Biotechnol, 2005, 68: 141-150
Wu G, Culley D E, Zhang W. Predicted highly expressed genes in the genomes of Streptomyces coelicolor and Streptomyces avermitilis and the implications for their metabolism. Microbiology, 2005,151: 2175-2187
Wu W, Leblanc S K, Piktel J, Jensen S E, Roy K L. Prediction and functional analysis of the replication origin of the linear plasmid pSCL2 in Streptomyces clavuligerus. Can J Microbiol, 2006, 2:293-300.
Wu X, Roy K L. Complete nucleotide sequence of a linear plasmid from Streptomyces clavuligerus and characterization of its RNA transcripts. J Bacteriol, 1993, 175:37-52.
Xu J, Tozawa Y, Lai C, Hayashi H, Ochi K. A rifampicin resistance mutation in the rpoB gene confers ppGpp-independent antibiotic production in Streptomyces coelicolor A3(2). Mol Genet Genomics, 2002, 268: 179-189
Xu M, Zhu Y, Zhang R, Shen M, Jiang W, Zhao G, and Qin Z. Characterization of the Genetic Components of Streptomyces lividans Linear Plasmid SLP2 for Replication in Circular and Linear Modes.J Bacteriol, 2006, 188: 6851-6857
Yong J H, Byeon, W H. Alternative production of avermectin components in Streptomyces avermitilis by gene replacement. J Microbiol, 2005, 43: 277-284
Yoon Y J, Kim E S, Hwang Y S, Choi C Y. Avermectin: biochemical and molecular basis of its biosynthesis and regulation. Appl Microbiol Biotechnol, 2004, 63: 626-634
Zakrzewska-Czerwinska J, Schrempf H. Characterization of an autonomously replicating region from the Streptomyces lividans chromosome. J Bacteriol, 1992, 174: 2688-2693
Zakrzewska-Czerwinska J, Majka J, Schrempf H. Minimal requirements of the Streptomyces lividans 66 oriC region and its transcriptional and translational activities. J Bacteriol, 1995,177: 4765-4771
Zaman S, Richards H, Ward J. Identification of the minimal replicon of the streptomycete plasmid pIJ101. Plasmid, 1993,29: 57-62
Zawilak-Pawlik A, Kois A, Majka J, Jakimowicz D, Smulczyk-Krawczyszyn A, Messer W, Zakrzewska-Czerwinska J. Architecture of bacterial replication initiation complexes: orisomes from four unrelated bacteria. Biochem J, 2005, 389: 471-481.
Zhang B C, Zhao Z H, Wang Y G, Ma, Q J. Construction of Saccharopolyspora erythraea M synthesizing a novel ketolide 3-deoxy-3-oxo-erythronolide B. Sheng Wu Gong Cheng Xue Bao, 2002,18: 198-203
Zhang R, Yang Y, Fang P, Jiang C, Xu L, Zhu Y, Shen M, Xia H, Zhao J, Chen T, Qin Z. Diversity of Telomere Palindromic Sequences and Replication Genes among Streptomyces Linear Plasmids. Appl Environ Microbiol, 2006, 72, 5728-5733