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链霉菌底盘细胞的开发现状及其应用
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基金项目:

国家“973”计划(2012CB721000,2011CBA00800);国家“863”计划(2012AA02A701);国家自然科学基金(31222002)


Progress in developing and applying Streptomyces chassis-A review
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    摘要:

    天然产物及其衍生物在现代医疗中扮演着举足轻重的角色,其生物活性多样性以及化学结构的丰富性是新药研发的源泉和动力。利用纯化学方法合成天然产物在技术和成本上有很大的困难,加上许多天然产物的原始产生菌具有培养条件苛刻、产量低下等缺点,而且大量基因簇在原始菌株中是沉默的,这使得利用合成生物学思想来指导天然产物生物合成基因簇的异源表达具有重大意义。作为抗生素、抗肿瘤活性物质、免疫抑制剂等次级代谢产物主要来源的放线菌一直是研究者们关注的焦点,特别是随着基因测序技术的飞速发展,人们发现链霉菌基因组中包含着极为丰富的天然产物生物合成基因簇资源。这意味着开发链霉菌底盘细胞作为异源表达宿主有其得天独厚的优势。本综述从底盘细胞开发的意义入手,重点阐述链霉菌底盘细胞构建的策略及现状,随后通过实例阐述了各种底盘链霉菌的实际应用。

    Abstract:

    Natural products and their derivatives play an important role in modern healthcare. Their diversity in bioactivity and chemical structure inspires scientists to discover new drug entities for clinical use. However, chemical synthesis of natural compounds has insurmountable difficulties in technology and cost. Also, many original-producing bacteria have disadvantages of needing harsh cultivation conditions, having low productivity and other shortcomings. In addition, some gene clusters responsible for secondary metabolite biosynthesis are silence in the original strains. Therefore, it is of great significance to exploit strategy for the heterologous expression of natural products guided by synthetic biology. Recently, researchers pay more attention on using actinomycetes that are the main source of many secondary metabolites, such as antibiotics, anticancer agents, and immunosuppressive drugs. Especially, with huge development of genome sequencing, abundant resources of natural product biosynthesis in Streptomyces have been discovered, which highlight the special advantages on developing Streptomyces as the heterologous expression chassis cells. This review begins with the significance of the development of Streptomyces chassis, focusing on the strategies and the status in developing Streptomyces chassis cells, followed by examples to illustrate the practical applications of a variety of Streptomyces chassis.

    参考文献
    [1] Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nature Reviews Drug Discovery, 2005, 4(3): 206-220.
    [2] Van Lanen SG, Shen B. Microbial genomics for the improvement of natural product discovery. Current Opinion in Microbiology, 2006, 9(3): 252-260.
    [3] Butler MS, Robertson AA, Cooper MA. Natural product and natural product derived drugs in clinical trials. Natural Product Reports, 2014, 31(11): 1612-1661.
    [4] Graening T, Schmalz HG. Total syntheses of colchicine in comparison: a journey through 50 years of synthetic organic chemistry. Angewandte Chemie International Edition, 2004, 43(25): 3230-3256.
    [5] Bérdy J. Thoughts and facts about antibiotics: where we are now and where we are heading. The Journal of Antibiotics, 2012, 65(8): 385-395.
    [6] Challis GL. Mining microbial genomes for new natural products and biosynthetic pathways. Microbiology, 2008, 154(6): 1555-1569.
    [7] Chiang YM, Chang SL, Oakley BR, Wang CC. Recent advances in awakening silent biosynthetic gene clusters and linking orphan clusters to natural products in microorganisms. Current Opinion in Chemical Biology, 2011, 15(1): 137-143.
    [8] Hopwood DA, Malpartida F, Kieser HM, Ikeda H, Duncan J, Fujii I, Rudd BAM, Floss HG, ōmura S. Production of “hybrid” antibiotics by genetic engineering. Nature, 1985, 314(6012): 642-644.
    [9] Young TS, Dorrestein PC, Walsh CT. Codon randomization for rapid exploration of chemical space in thiopeptide antibiotic variants. Chemistry & Biology, 2012, 19(12): 1600-1610.
    [10] Circello BT, Eliot AC, Lee JH, van der Donk WA, Metcalf WW. Molecular cloning and heterologous expression of the dehydrophos biosynthetic gene cluster. Chemistry & Biology, 2010, 17(4): 402-411.
    [11] Owen JG, Copp JN, Ackerley DF. Rapid and flexible biochemical assays for evaluating 4'-phosphopantetheinyl transferase activity. Biochemical Journal, 2011, 436(3): 709-717.
    [12] Ongley SE, Bian XY, Neilan BA, Müller R. Recent advances in the heterologous expression of microbial natural product biosynthetic pathways. Natural Product Reports, 2013, 30(8): 1121-1138.
    [13] Wenzel SC, Müller R. Recent developments towards the heterologous expression of complex bacterial natural product biosynthetic pathways. Current Opinion in Biotechnology, 2005, 16(6): 594-606.
    [14] Pfeifer BA, Wang CCC, Walsh CT, Khosla C. Biosynthesis of yersiniabactin, a complex polyketide-nonribosomal peptide, using Escherichia coli as a heterologous host. Applied and Environmental Microbiology, 2003, 69(11): 6698-6702.
    [15] Minami H, Kim JS, Ikezawa N, Takemura T, Katayama T, Kumagai H, Sato F. Microbial production of plant benzylisoquinoline alkaloids. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(21): 7393-7398.
    [16] Donnez D, Jeandet P, Clément C, Courot E. Bioproduction of resveratrol and stilbene derivatives by plant cells and microorganisms. Trends in Biotechnology, 2009, 27(12): 706-713.
    [17] Bérdy J. Bioactive microbial metabolites. The Journal of Antibiotics, 2005, 58(1): 1-26.
    [18] Bentley SD, Chater KF, Cerdeño-Tárraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang CH, Kieser T, Larke L, Murphy L, Oliver K, O'Neil S, Rabbinowitsch E, Rajandream MA, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, Barrell BG, Parkhill J, Hopwood DA. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature, 2002, 417(6885): 141-147.
    [19] Challis GL, Hopwood DA. Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(suppl 2): 14555-14561.
    [20] Ikeda H, Ishikawa J, Hanamoto A, Shinose M, Kikuchi H, Shiba T, Sakaki Y, Hattori M, ōmura S. Complete genome sequence and comparative analysis of the industrial microorganism Streptomyces avermitilis. Nature Biotechnology, 2003, 21(5): 526-531.
    [21] ōmura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M, Takahashi Y, Horikawa H, Nakazawa H, Osonoe T, 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. Proceedings of the National Academy of Sciences of the United States of America, 2001, 98(21): 12215-12220.
    [22] Zhang HR, Wang Y, Wu JQ, Skalina K, Pfeifer BA. Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host. Chemistry & Biology, 2010, 17(11): 1232-1240.
    [23] Watanabe K, Hotta K, Praseuth AP, Koketsu K, Migita A, Boddy CN, Wang CCC, Oguri H, Oikawa H. Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. Nature Chemical Biology, 2006, 2(8): 423-428.
    [24] Ajikumar PK, Xiao WH, Tyo KEJ, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G. Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science, 2010, 330(6000): 70-74.
    [25] Beekwilder J, Wolswinkel R, Jonker H, Hall R, de Vos CHR, Bovy A. Production of resveratrol in recombinant microorganisms. Applied and Environmental Microbiology, 2006, 72(8): 5670-5672.
    [26] Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Jiang H, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD. High-level semi-synthetic production of the potent antimalarial artemisinin. Nature, 2013, 496(7446): 528-532.
    [27] Brown S, Clastre M, Courdavault V, O'Connor SE. De novo production of the plant-derived alkaloid strictosidine in yeast. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(11): 3205-3210.
    [28] Chiang YM, Oakley CE, Ahuja M, Entwistle R, Schultz A, Chang SL, Sung CT, Wang CCC, Oakley BR. An efficient system for heterologous expression of secondary metabolite genes in Aspergillus nidulans. Journal of the American Chemical Society, 2013, 135(20): 7720-7731.
    [29] Yin WB, Chooi YH, Smith AR, Cacho RA, Hu YC, White TC, Tang Y. Discovery of cryptic polyketide metabolites from dermatophytes using heterologous expression in Aspergillus nidulans. ACS Synthetic Biology, 2013, 2(11): 629-634.
    [30] Mushegian A. The minimal genome concept. Current Opinion in Genetics & Development, 1999, 9(6): 709-714.
    [31] Komatsu M, Uchiyama T, ōmuraprotein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2). Journal of Bacteriology, 1996, 178(24): 7276-7284.
    [48] Penn JL, Li X, Whiting A, Latif M, Gibson T, Silva CJ, Brian P, Davies J, Miao V, Wrigley SK, Baltz RH. Heterologous production of daptomycin in Streptomyces lividans. Journal of Industrial Microbiology and Biotechnology, 2006, 33(2): 121-128.
    [49] Kieser T, Bibb M J, Buttner MJ, Chater KF, Hopwood DA, Centre JI, Park NR. Practical Streptomyces genetics. Norwich, UK: The John Innes Foundation, 2000.
    [50] Thanapipatsiri A, Claesen J, Gomez-Escribano JP, Bibb M, Thamchaipenet A. A Streptomyces coelicolor host for the heterologous expression of Type III polyketide synthase genes. Microbial Cell Factories, 2015, 14: 145.
    [51] Völler GH, Krawczyk JM, Pesic A, Krawczyk B, Nachtigall J, Süssmuth RD. Characterization of new class III lantibiotics-erythreapeptin, avermipeptin and griseopeptin from Saccharopolyspora erythraea, Streptomyces avermitilis and Streptomyces griseus demonstrates stepwise N-terminal leader processing. ChemBioChem, 2012? 13(8): 1174-1183.
    [52] Li T, Du YY, Cui Q, Zhang JT, Zhu WM, Hong K, Li WL. Cloning, characterization and heterologous expression of the indolocarbazole biosynthetic gene cluster from marine-derived Streptomyces sanyensis FMA. Marine Drugs, 2013, 11(2): 466-488.
    [53] Kaysser L, Bernhardt P, Nam SJ, Loesgen S, Ruby JG, Skewes-Cox P, Jensen PR, Fenical W, Moore BS. Merochlorins A-D, cyclic meroterpenoid antibiotics biosynthesized in divergent pathways with vanadium-dependent chloroperoxidases. Journal of the American Chemical Society, 2012, 134(29): 11988-11991.
    [54] Zaburannyi N, Rabyk M, Ostash B, Fedorenko V, Luzhetskyy A. Insights into naturally minimised Streptomyces albus J1074 genome. BMC Genomics, 2014, 15: 97.
    [55] Lombó F, Velasco A, Castro A, De la Calle F, Braña AF, Sánchez-Puelles JM, Méndez C, Salas JA. Deciphering the biosynthesis pathway of the antitumor thiocoraline from a marine actinomycete and its expression in two Streptomyces species. ChemBioChem, 2006, 7(2): 366-376.
    [56] Baltz RH. Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters. Journal of Industrial Microbiology & Biotechnology, 2010, 37(8): 759-772.
    [57] Gullón S, Olano C, Abdelfattah MS, Braña AF, Rohr J, Méndez C, Salas JA. Isolation, characterization, and heterologous expression of the biosynthesis gene cluster for the antitumor anthracycline steffimycin. Applied and Environmental Microbiology, 2006, 72(6): 4172-4183.
    [58] Wendt-Pienkowski E, Huang Y, Zhang J, Li BS, Jiang H, Kwon H, Hutchinson CR, Shen B. Cloning, sequencing, analysis, and heterologous expression of the fredericamycin biosynthetic gene cluster from Streptomyces griseus. Journal of the American Chemical Society, 2005, 127(47): 16442-16452.
    [59] Makitrynskyy R, Rebets Y, Ostash B, Zaburannyi N, Rabyk M, Walker S, Fedorenko V. Genetic factors that influence moenomycin production in streptomycetes. Journal of Industrial Microbiology & Biotechnology, 2010, 37(6): 559-566.
    [60] Bilyk B, Luzhetskyy A. Unusual site-specific DNA integration into the highly active pseudo-attB of the Streptomyces albus J1074 genome. Applied Microbiology and Biotechnology, 2014, 98(11): 5095-5104.
    [61] Pullan ST, Chandra G, Bibb MJ, Merrick M. Genome-wide analysis of the role of GlnR in Streptomyces venezuelae provides new insights into global nitrogen regulation in actinomycetes. BMC Genomics, 2011, 12: 175.
    [62] Hong JSJ, Park SH, Choi CY, Sohng JK, Yoon YJ. New olivosyl derivatives of methymycin/pikromycin from an engineered strain of Streptomyces venezuelae. FEMS Microbiology Letters, 2004, 238(2): 391-399.
    [63] Park JW, Hong JSJ, Parajuli N, Jung WS, Park SR, Lim SK, Sohng JK, Yoon YJ. Genetic dissection of the biosynthetic route to gentamicin A2 by heterologous expression of its minimal gene set. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(24): 8399-8404.
    [64] Park JW, Park SR, Nepal KK, Han AR, Ban YH, Yoo YJ, Kim EJ, Kim EM, Kim D, Sohng JK, Yoon YJ. Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation. Nature Chemical Biology, 2011, 7(11): 843-852.
    [65] Jung WS, Lee SK, Hong JSJ, Park SR, Jeong SJ, Han AR, Sohng JK, Kim BG, Choi CY, Sherman DH, Yoon YJ. Heterologous expression of tylosin polyketide synthase and production of a hybrid bioactive macrolide in Streptomyces venezuelae. Applied Microbiology and Biotechnology, 2006, 72(4): 763-769.
    [66] Park SR, Park JW, Jung WS, Han AR, Ban YH, Kim EJ, Sohng JK, Sim SJ, Yoon YJ. Heterologous production of epothilones B and D in Streptomyces venezuelae. Applied Microbiology and Biotechnology, 2008, 81(1): 109-117.
    [67] Borisova SA, Zhang CS, Takahashi H, Zhang H, Wong AW, Thorson JS, Liu HW. Substrate specificity of the macrolide-glycosylating enzyme pair DesVII/DesVIII: opportunities, limitations and mechanistic hypotheses. Angewandte Chemie International Edition, 2006, 45(17): 2748-2753.
    [68] Jung WS, Han AR, Hong JSJ, Park SR, Choi CY, Park JW, Yoon YJ. Bioconversion of 12-, 14- and 16-membered ring aglycones to glycosylated macrolides in an engineered strain of Streptomyces venezuelae. Applied Microbiology and Biotechnology, 2007, 76(6): 1373-1381.
    [69] Han AR, Park SR, Park JW, Lee EY, Kim DM, Kim BG, Yoon YJ. Biosynthesis of glycosylated derivatives of tylosin in Streptomyces venezuelae. Journal of Microbiology and Biotechnology, 2011, 21(6): 613-616.
    [70] Han AR, Park JW, Lee MK, Ban YH, Yoo YJ, Kim EJ, Kim E, Kim BG, Sohng JK, Yoon YJ. Development of a Streptomyces venezuelae-based combinatorial biosynthetic system for the production of glycosylated derivatives of doxorubicin and its biosynthetic intermediates. Applied and Environmental Microbiology, 2011, 77(14): 4912-4923.
    [71] Gomez-Escribano JP, Bibb MJ. Heterologous expression of natural product biosynthetic gene clusters in Streptomyces coelicolor: from genome mining to manipulation of biosynthetic pathways. Journal of Industrial Microbiology & Biotechnology, 2014, 41(2): 425-431.
    [72] Saleh O, Bonitz T, Flinspach K, Kulik A, Burkard N, Mühlenweg A, Vente A, Polnick S, Lämmerhofer M, Gust B, Fiedler HP, Heide L. Activation of a silent phenazine biosynthetic gene cluster reveals a novel natural product and a new resistance mechanism against phenazines. Medchemcomm, 2012, 3(8): 1009-1019.
    [73] Saleh O, Flinspach K, Westrich L, Kulik A, Gust B, Fiedler HP, Heide L. Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663. Beilstein Journal of Organic Chemistry, 2012, 8: 501-513.
    [74] Smanski MJ, Casper J, Peterson RM, Yu ZG, Rajski SR, Shen B. Expression of the platencin biosynthetic gene cluster in heterologous hosts yielding new platencin congeners. Journal of Natural Products, 2012, 75(12): 2158-2167.
    [75] Foulston L. Cloning and analysis of the microbisporicin lantibiotic gene cluster from Microbispora corallina. The University of East Anglia Doctoral Thesis, 2010.
    [76] Foulston LC, Bibb MJ. Microbisporicin gene cluster reveals unusual features of lantibiotic biosynthesis in actinomycetes. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(30): 13461-13466.
    [77] Wang T, Bai LQ, Zhu DQ, Lei X, Liu G, Deng ZX, You DL. Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes. Enzyme and Microbial Technology, 2012, 50(1): 5-9.
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肖丽萍,邓子新,刘天罡. 链霉菌底盘细胞的开发现状及其应用[J]. 微生物学报, 2016, 56(3): 441-453

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  • 收稿日期:2015-09-27
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