链霉菌较小基因组构建的研究进展

doi:10.16288/j.yczz.25-008

遗传 ›› 2025, Vol. 47 ›› Issue (7): 756-767.doi: 10.16288/j.yczz.25-008

链霉菌较小基因组构建的研究进展

李慧(), 郭莉娟, 周贺霞, 李春阳, 代佳琳, 谌立祝, 张锐, 孙丰慧()

成都医学院检验医学院，成都 610500

收稿日期:2025-03-01 修回日期:2025-04-21 出版日期:2025-07-20 发布日期:2025-04-28
通讯作者: 孙丰慧，博士，教授，研究方向：天然产物研究开发，微生物耐药机制方面研究。E-mail: sunfenghui@cmc.edu.cn
作者简介:李慧，博士，实验师，研究方向：链霉菌细胞工厂开发，微生物耐药机制方面研究。E-mail: huili@cmc.edu.cn
基金资助:
成都医学院校基金(CYZYB24-07);四川省动物源性食品兽药残留防控技术工程实验室开放基金(24LHGCSYS1-04);四川省动物源性食品兽药残留防控技术工程实验室开放基金(24LHGCSYS1-06);发育与再生四川省重点实验室开放基金(24LHFYSZ1-48)

Progress on the construction of Streptomyces minimized genomes

Hui Li(), Lijuan Guo, Hexia Zhou, Chunyang Li, Jialin Dai, Lizhu Shen, Rui Zhang, Fenghui Sun()

School of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, China

Received:2025-03-01 Revised:2025-04-21 Published:2025-07-20 Online:2025-04-28
Supported by:
School-level Fund of Chengdu Medical College(CYZYB24-07);Open Fund of Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin(24LHGCSYS1-04);Open Fund of Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin(24LHGCSYS1-06);Open Fund of Development and Regeneration Key Laboratory of Sichuan Province(24LHFYSZ1-48)

摘要/Abstract

摘要：

链霉菌(Streptomyces)作为天然药物合成的重要模式菌，具有合成多种生物活性物质的潜力，有超过2/3的抗生素由链霉菌产生。然而，许多链霉菌的原始生产菌株存在着不易培养、生长缓慢、遗传操作困难等问题，这使得通过遗传改造的方式来提高目标化合物产量的策略受到了限制，同时本底产生的代谢物也会对目标天然产物的分离和提取产生一定的干扰。因此，开发生长快速、代谢背景清晰、遗传操作简单的链霉菌底盘细胞作为宿主，能解决天然药物产量低、生产成本高等问题。本文结合前期的研究工作，对链霉菌较小基因组的设计、构建及其在天然产物发掘和生产中的应用进行了综述，以期为利用链霉菌合成天然产物提供参考和借鉴。

关键词: 链霉菌, 较小基因组, 天然产物

Abstract:

The genus Streptomyces provides a wealth of natural products with diverse structures, accounting for more than two-thirds of natural antibiotics. However, the original Streptomyces producers of desired natural products are technically challenging due to their harsh cultivation conditions, slow growth rate and intricate genetic backgrounds. Meanwhile, the metabolites of Streptomyces can also cause interference with the extraction of the target natural products. Thus, there is an urgent need to develop an ideal Streptomyces chassis with characterization of clean metabolic background, fluent genetic manipulation, and higher success rate of biosynthetic gene cluster expressions, which can largely increase yield and reduce production costs of natural products. In this review, we summarize the recent development of the chassis in Streptomyces and its important roles in the excavation and production of natural products, with focus on its potential for discovery and synthesis of natural products.

Key words: Streptomyces, minimal genome, natural products

李慧, 郭莉娟, 周贺霞, 李春阳, 代佳琳, 谌立祝, 张锐, 孙丰慧. 链霉菌较小基因组构建的研究进展[J]. 遗传, 2025, 47(7): 756-767.

Hui Li, Lijuan Guo, Hexia Zhou, Chunyang Li, Jialin Dai, Lizhu Shen, Rui Zhang, Fenghui Sun. Progress on the construction of Streptomyces minimized genomes[J]. Hereditas(Beijing), 2025, 47(7): 756-767.

图/表 3

参考文献 83

[1]	Zhou Q, Ning SQ, Luo YZ. Coordinated regulation for nature products discovery and overproduction in Streptomyces. Synth Syst Biotechnol, 2020, 5(2): 49-58. pmid: 32346621
[2]	Deng L, Zhao ZH, Liu L, Zhong ZY, Xie WX, Zhou F, Xu W, Zhang YB, Deng ZX, Sun YH. Dissection of 3D chromosome organization in Streptomyces coelicolor A3(2) leads to biosynthetic gene cluster overexpression. Proc Natl Acad Sci USA, 2023, 120(11): 1-11. pmid: 36877856
[3]	Li SS, Li ZL, Pang S, Xiang WS, Wang WS. Coordinating precursor supply for pharmaceutical polyketide production in Streptomyces. Curr Opin Biotechnol, 2021, 69: 26-34. pmid: 33316577
[4]	Liu ZY, Zhao YT, Huang CQ, Luo YZ. Recent advances in silent gene cluster activation in Streptomyces. Front Bioeng Biotechnol, 2021, 9: 632230. pmid: 33681170
[5]	Xu ZW, Ji LH, Tang WX, Guo L, Gao C, Chen XL, Liu J, Hu GP, Liu LM. Metabolic engineering of Streptomyces to enhance the synthesis of valuable natural products. Eng Microbiol, 2022, 2(2): 1-8. pmid: 39628845
[6]	Alam K, Mazumder A, Sikdar A, Zhao YM, Hao JF, Song CY, Wang YY, Sarkar R, Islam S, Zhang YM, Li AY. Streptomyces: the biofactory of secondary metabolites. Front Microbiol, 2022, 13: 968053. pmid: 36246257
[7]	Liu R, Deng ZX, Liu TG. Streptomyces species: ideal chassis for natural product discovery and overproduction. Metab Eng, 2018, 50: 74-84. pmid: 29852270
[8]	Bu QT, Li YP, Xie H, Wang J, Li ZY, Chen XA, Mao XM, Li YQ. Comprehensive dissection of dispensable genomic regions in Streptomyces based on comparative analysis approach. Microb Cell Fact, 2020, 19(1): 99. pmid: 32375781
[9]	Mizoguchi H, Mori H, Fujio T. Escherichia coli minimum genome factory. Biotechnol Appl Biochem, 2007, 46(Pt 3): 157-167. pmid: 17300222
[10]	Liang PX, Zhang YT, Xu B, Zhao YX, Liu XS, Gao WX, Ma T, Yang C, Wang SF, Liu RH. Deletion of genomic islands in the Pseudomonas putida KT2440 genome can create an optimal chassis for synthetic biology applications. Microb Cell Fact, 2020, 19(1): 70. pmid: 32188438
[11]	Martinez-Garcia E, de Lorenzo V. Pseudomonas putida as a synthetic biology chassis and a metabolic engineering platform. Curr Opin Biotechnol, 2024, 85: 103025. pmid: 38061264
[12]	Qiu SW, Yang BW, Li ZL, Li SS, Yan H, Xin ZG, Liu JF, Zhao XJ, Zhang LX, Xiang WS, Wang WS. Building a highly efficient Streptomyces super-chassis for secondary metabolite production by reprogramming naturally-evolved multifaceted shifts. Metab Eng, 2024, 81: 210-226. pmid: 38142854
[13]	Liu JQ, Zhou HB, Yang ZY, Wang X, Chen HN, Zhong L, Zheng WT, Niu WJ, Wang S, Ren XM, Zhong GN, Wang Y, Ding XM, Müller R, Zhang YM, Bian XY. Rational construction of genome-reduced Burkholderiales chassis facilitates efficient heterologous production of natural products from proteobacteria. Nat Commun, 2021, 12(1): 4347. pmid: 34301933
[14]	Bu QT, Yu P, Wang J, Li ZY, Chen XA, Mao XM, Li YQ. Rational construction of genome-reduced and high- efficient industrial Streptomyces chassis based on multiple comparative genomic approaches. Microb Cell Fact, 2019, 18(1): 16. pmid: 30691531
[15]	Li H, Gao S, Shi SY, Zhao XM, Ye HY, Luo YZ. Rational construction of genome-minimized Streptomyces host for the expression of secondary metabolite gene clusters. Synth Syst Biotechnol, 2024, 9(3): 600-608. pmid: 38774831
[16]	Komatsu M, Komatsu K, Koiwai H, Yamada Y, Kozone I, Izumikawa M, Hashimoto J, Takagi M, Omura S, Shin-Ya K, Cane DE, Ikeda H. Engineered Streptomyces avermitilis host for heterologous expression of biosynthetic gene cluster for secondary metabolites. ACS Synth Biol, 2013, 2(7): 384-396. pmid: 23654282
[17]	Hopwood DA. Soil to genomics: the Streptomyces chromosome. Annu Rev Genet, 2006, 40: 1-23. pmid: 16761950
[18]	Ikeda H, Kazuo SY, Omura S. Genome mining of the Streptomyces avermitilis genome and development of genome-minimized hosts for heterologous expression of biosynthetic gene clusters. J Ind Microbiol Biotechnol, 2014, 41(2): 233-250. pmid: 23990133
[19]	Zaburannyi N, Rabyk M, Ostash B, Fedorenko V, Luzhetskyy A. Insights into naturally minimised Streptomyces albus J1074 genome. BMC Genomics, 2014, 15: 97. pmid: 24495463
[20]	Thornburg ZR, Bianchi DM, Brier TA, Gilbert BR, Earnest TM, Melo MCR, Safronova N, Sáenz JP, Cook AT, Wise KS,Hutchison CA 3rd, Smith HO, Glass JI, Luthey-Schulten Z. Fundamental behaviors emerge from simulations of a living minimal cell. Cell, 2022, 185(2): 345-360. pmid: 35063075
[21]	Guo YX, Ju Y, Chen D, Wang LH. Research on the computational prediction of essential genes. Front Cell Dev Biol, 2021, 9: 803608. pmid: 34938741
[22]	Gerdes SY, Scholle MD, Campbell JW, Balázsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabási AL, Oltvai ZN, Osterman AL. Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J Bacteriol, 2003, 185(19): 5673-5684. pmid: 13129938
[23]	Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H, Chu AM, Connelly C, Davis K, Dietrich F, Dow SW, El Bakkoury M, Foury F, Friend SH, Gentalen E, Giaever G, Hegemann JH, Jones T, Laub M, Liao H, Liebundguth N, Lockhart DJ, Lucau-Danila A, Lussier M, M'rabet N, Menard P, Mittmann M, Pai C, Rebischung C, Revuelta JL, Riles L, Roberts CJ, Ross-Macdonald P, Scherens B, Snyder M, Sookhai-Mahadeo S, Storms RK, Veronneau S, Voet M, Volckaert G, Ward TR, Wysocki R, Yen GS, Yu K, Zimmermann K, Philippsen P, Johnston M, Davis RW. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science, 1999, 285(5429): 901-906. pmid: 10436161
[24]	Stahl M, Stintzi A. Identification of essential genes in C. jejuni genome highlights hyper-variable plasticity regions. Funct Integr Genomics, 2011, 11(2): 241-257. pmid: 21344305
[25]	Zhou M, Jing XY, Xie PF, Chen WH, Wang T, Xiao HY, Qin ZJ. Sequential deletion of all the polyketide synthase and nonribosomal peptide synthetase biosynthetic gene clusters and a 900-kb subtelomeric sequence of the linear chromosome of Streptomyces coelicolor. Fems Microbiol Letter, 2012, 333(2): 169-179. pmid: 22670631
[26]	Vickers CE, Blank LM, Krömer JO. Grand challenge commentary: chassis cells for industrial biochemical production. Nat Chem Biol, 2010, 6(12): 875-877. pmid: 21079595
[27]	Hamedirad M, Chao R, Weisberg S, Lian JZ, Sinha S, Zhao HM. Towards a fully automated algorithm driven platform for biosystems design. Nat Commun, 2019, 10(1): 5150. pmid: 31723141
[28]	Hwang S, Lee Y, Kim JH, Kim G, Kim H, Kim W, Cho S, Palsson BO, Cho BK. Streptomyces as microbial chassis for heterologous protein expression. Front Bioeng Biotechy, 2021, 9: 804295. pmid: 34993191
[29]	Mushegian A. The minimal genome concept. Curr Opin Genet Dev, 1999, 9(6): 709-714. pmid: 10607608
[30]	Shen XM, Wang Z, Huang XQ, Hu HB, Wang W, Zhang XH. Developing genome-reduced Pseudomonas chlororaphis strains for the production of secondary metabolites. BMC Genomics, 2017, 18(1): 715. pmid: 28893188
[31]	He Q, Wang Q, ZHU QH, Fang HQ. Application progress of genome engineering for construction of microbial cell factories. Biotechnology & Business, 2017, (1): 31-37.
	何庆, 王茜, 朱清华, 方宏清. 基因组工程在微生物细胞工厂构建中的应用进展. 生物产业技术, 2017, (1): 31-37.
[32]	Li JY, Yang S, Cui YJ, Wang T, Teng Y. Research progress of bacterial minimal genome. Hereditas(Beijing), 2021, 43(2): 142-159.
	李金玉, 杨姗, 崔玉军, 王涛, 滕越. 细菌最小基因组研究进展. 遗传, 2021, 43(2): 142-159.
[33]	Zhang F, Huo KY, Song XY, Quan YF, Wang SF, Zhang ZL, Gao WX, Yang C. Engineering of a genome-reduced strain Bacillus amyloliquefaciens for enhancing surfactin production. Microb Cell Fact, 2020, 19(1): 223. pmid: 33287813
[34]	Yang YF, Gen BN, Song HY, He QN, He MX, Bao J, Bai FW, Yang SH. Progress and perspectives on developing Zymomonas mobilis as a chassis cell. Synth Biol J, 2021, 2(1): 59-90.
	杨永富, 耿碧男, 宋皓月, 何桥宁, 何明雄, 鲍杰, 白凤武, 杨世辉. 运动发酵单胞菌底盘细胞研究现状及展望. 合成生物学, 2021, 2(1): 59-90.
[35]	Cobb RE, Wang YJ, Zhao HM. High-efficiency multiplex genome editing of Streptomyces species using an engineered CRISPR/Cas system. ACS Synth Biol, 2015, 4(6): 723-728. pmid: 25458909
[36]	de Lorenzo V. Chassis organism from Corynebacterium glutamicum: the way towards biotechnological domestication of Corynebacteria. Biotechnol J, 2015, 10(2): 244-245. pmid: 25293499
[37]	Fredens J, Wang KH, de La Torre D, Funke LFH, Robertson WE, Christova Y, Chia T, Schmied WH, Dunkelmann DL, Beránek V, Uttamapinant C, Llamazares AG, Elliott TS, Chin JW. Total synthesis of Escherichia coli with a recoded genome. Nature, 2019, 569(7757): 514-518. pmid: 31092918
[38]	Wang HL, Li Z, Jia RN, Yin J, Li AY, Xia LQ, Yin YL, Müller R, Fu J, Stewart AF, Zhang YM. ExoCET: exonuclease in vitro assembly combined with RecET recombination for highly efficient direct DNA cloning from complex genomes. Nucleic Acids Res, 2018, 46(5): 2697. pmid: 29272442
[39]	Shao ZY, Zhao H, Zhao HM. DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Res, 2009, 37(2): e16. pmid: 19074487
[40]	Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA 3rd, Smith HO. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods, 2009, 6(5): 343-345. pmid: 19363495
[41]	Engler C, Kandzia R, Marillonnet S. A one pot, one step, precision cloning method with high throughput capability. PLoS One, 2008, 3(11): e3647. pmid: 18985154
[42]	Xie ZX, Li BZ, Mitchell LA, Wu Y, Qi X, Jin Z, Jia B, Wang X, Zeng BX, Liu HM, Wu XL, Feng Q, Zhang WZ, Liu W, Din MZ, Li X, Zhao GR, Qiao JJ, Cheng JS, Zhao M, Kuang Z, Wang XY, Martin JA, Stracquadanio G, Yang K, Bai X, Zhao J, Hu ML, Lin QH, Zhang WQ, Shen MH, Chen S, Su W, Wang EX, Guo R, Zhai F, Guo XJ, Du HX, Zhu JQ, Song TQ, Dai JJ, Li FF, Jiang GZ, Han SL, Liu SY, Yu ZC, Yang XN, Chen K, Hu C, Li DS, Jia N, Liu Y, Wang LT, Wang S, Wei XT, Fu MQ, Qu LM, Xin SY, Liu T, Tian KR, Li XN, Zhang JH, Song LX, Liu JG, Lv JF, Xu H, Tao R, Wang Y, Zhang TT, Deng YX, Wang YR, Li T, Ye GX, Xu XR, Xia ZB, Zhang W, Yang SL, Liu YL, Ding WQ, Liu ZN, Zhu JQ, Liu NZ, Walker R, Luo YS, Wang Y, Shen Y, Yang HM, Cai YZ, Ma PS, Zhang CT, Bader JS, Boeke JD, Yuan YJ. "Perfect" designer chromosome V and behavior of a ring derivative. Science, 2017, 355(6329): eaaf4704. pmid: 28280151
[43]	Zhao Y, Coelho C, Hughes AL, Lazar-Stefanita L, Yang S, Brooks AN, Walker RSK, Zhang WM, Lauer S, Hernandez C, Cai JT, Mitchell LA, Agmon N, Shen Y, Sall J, Fanfani V, Jalan A, Rivera J, Liang FX, Bader JS, Stracquadanio G, Steinmetz LM, Cai YZ, Boeke JD. Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions. Cell, 2023, 186(24): 5220-5236.e16. pmid: 37944511
[44]	Rudolph B, Gebendorfer KM, Buchner J, Winter J. Evolution of Escherichia coli for growth at high temperatures. J Biol Chem, 2010, 285(25): 19029-19034. pmid: 20406805
[45]	Yu XY, Li S, Feng HB, Liao XH, Xing XH, Bai ZH, Liu XX, Zhang C. CRISPRi-microfluidics screening enables genome-scale target identification for high-titer protein production and secretion. Metab Eng, 2023, 75: 192-204. pmid: 36572334
[46]	Long CP, Gonzalez JE, Feist AM, Palsson BO, Antoniewicz MR. Dissecting the genetic and metabolic mechanisms of adaptation to the knockout of a major metabolic enzyme in Escherichia coli. Proc Natl Acad Sci USA, 2018, 115(1): 222-227. pmid: 29255023
[47]	Choe DH, Lee JH, Yoo M, Hwang S, Sung BH, Cho S, Palsson B, Kim SC, Cho BK. Adaptive laboratory evolution of a genome-reduced Escherichia coli. Nat Commun, 2019, 10(1): 935. pmid: 30804335
[48]	Seok JY, Han YH, Yang JS, Yang JN, Lim HG, Kim SG, Seo SW, Jung GY. Synthetic biosensor accelerates evolution by rewiring carbon metabolism toward a specific metabolite. Cell Rep, 2021, 36(8): 109589. pmid: 34433019
[49]	Shi SY, Xie YH, Wang GL, Luo YZ. Metabolite-based biosensors for natural product discovery and overproduction. Curr Opin Biotechnol, 2022, 75: 102699. pmid: 35231771
[50]	BU QT, Mao XM, Chen XA, Li YQ. Progress and prospect of genome-minimized Streptomyces hosts. China Life Sci, 2019, 31(4): 391-401.
	卜庆廷, 毛旭明, 陈新爱, 李永泉. 链霉菌较小基因组研究进展及展望. 生命科学, 2019, 31(4): 391-401.
[51]	Xiao LP, Deng ZX, Liu TG. Progress in developing and applying Streptomyces chassis--a review. Acta Microbiologica Sin, 2016, 56(3): 441-453.
	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. 微生物学报, 2016, 56(3): 441-453.
[52]	Yan H, Li SS, Wang WS. Reprogramming naturally evolved switches for Streptomyces chassis development. Trends Biotechnol, 2025, 43(1): 12-15. pmid: 39054219
[53]	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(21): 12215-12220. pmid: 11572948
[54]	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(5): 526-531. pmid: 12692562
[55]	Yamada Y, Arima S, Nagamitsu T, Johmoto K, Uekusa H, Eguchi T, Shin-Ya K, Cane DE, Ikeda H. Novel terpenes generated by heterologous expression of bacterial terpene synthase genes in an engineered Streptomyces host. J Antibiot (Tokyo), 2015, 68(6): 385-394. pmid: 25605043
[56]	Komatsu M, Uchiyama T, Omura S, Cane DE, Ikeda H. Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism. Proc Natl Acad Sci USA, 2010, 107(6): 2646-2651. pmid: 20133795
[57]	Gomez-Escribano JP, Bibb MJ. Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters. Microb Biotechnol, 2011, 4(2): 207-215. pmid: 21342466
[58]	Myronovskyi M, Rosenkränzer B, Nadmid S, Pujic P, Normand P, Luzhetskyy A. Generation of a cluster-free Streptomyces albus chassis strains for improved heterologous expression of secondary metabolite clusters. Metab Eng, 2018, 49: 316-324. pmid: 30196100
[59]	Ahmed Y, Rebets Y, Estévez MR, Zapp J, Myronovskyi M, Luzhetskyy A. Engineering of Streptomyces lividans for heterologous expression of secondary metabolite gene clusters. Microb Cell Fact, 2020, 19(1): 5. pmid: 31918711
[60]	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. pmid: 12000953
[61]	Ziermann R, Betlach MC. Recombinant polyketide synthesis in Streptomyces: engineering of improved host strains. Biotechniques, 1999, 26(1): 106-110. pmid: 9894599
[62]	Dangel V, Westrich L, Smith MCM, Heide L, Gust B. Use of an inducible promoter for antibiotic production in a heterologous host. Appl Microbiol Biotechnol, 2010, 87(1): 261-269. pmid: 20127238
[63]	Kepplinger B, Morton-Laing S, Seistrup KH, Marrs ECL, Hopkins AP, Perry JD, Strahl H, Hall MJ, Errington J, Allenby NEE. Mode of action and heterologous expression of the natural product antibiotic vancoresmycin. ACS Chem Biol, 2018, 1(13): 207-214. pmid: 29185696
[64]	Li L, Zheng GS, Chen J, Ge M, Jiang WH, Lu YH. Multiplexed site-specific genome engineering for overproducing bioactive secondary metabolites in actinomycetes. Metab Eng, 2017, 40: 80-92. pmid: 28088540
[65]	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. J Am Chem Soc, 2005, 127(47): 16442-16452. pmid: 16305230
[66]	Feng ZY, Wang LY, Rajski SR, Xu ZN, Coeffet-Legal MF, Shen B. Engineered production of iso-migrastatin in heterologous Streptomyces hosts. Bioorg Med Chem, 2009, 17(6): 2147-2153. pmid: 19010685
[67]	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. Appl Environ Microbiol, 2006, 72(6): 4172-4183. pmid: 16751529
[68]	Lu CY, Zhang XJ, Jiang M, Bai LQ. Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus. Metab Eng, 2016, 35: 129-137. pmid: 26969249
[69]	Fazal A, Thankachan D, Harris E, Seipke RF. A chromatogram-simplified Streptomyces albus host for heterologous production of natural products. Antonie Van Leeuwenhoek, 2020, 113(4): 511-520. pmid: 31781915
[70]	Hu YL, Zhang Q, Liu SH, Sun JL, Yin FZ, Wang ZR, Shi J, Jiao RH, Ge HM. Building Streptomyces albus as a chassis for synthesis of bacterial terpenoids. Chem Sci, 2023, 14(13): 3661-3667. pmid: 37006697
[71]	Chen S, Huang X, Zhou XF, Bai LQ, He J, Jeong KJ, Lee SY, Deng ZX. Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex. Chem Biol, 2003, 10(11): 1065-1076. pmid: 14652074
[72]	CDC: antibiotic-resistant bugs on rise in ICUs. Patient Focus Care Satisf, 1999, 7(5): 54-55. pmid: 10558148
[73]	Xu YS, Gao TL, Yu H, Deng ZX, He XY. Curing linear plasmids by nitrosoguanidine in Streptomyces sp. FR-008. Microbiol China, 2017, 44(1): 1-9.
	徐玉松, 高土玲, 于昊, 邓子新, 贺新义. 亚硝基胍消除链霉菌FR-008的线性质粒. 微生物学通报, 2017, 44(1): 1-9.
[74]	Felnagle EA, Rondon MR, Berti AD, Crosby HA, Thomas MG. Identification of the biosynthetic gene cluster and an additional gene for resistance to the antituberculosis drug capreomycin. Appl Environ Microbiol, 2007, 73(13): 4162-4170. pmid: 17496129
[75]	Miao V, Coeffet-Legal MF, Brian P, Brost R, Penn J, Whiting A, Martin S, Ford R, Parr I, Bouchard M, Silva CJ, Wrigley SK, Baltz RH. Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry. Microbiology (Reading), 2005, 151(Pt 5): 1507-1523. pmid: 15870461
[76]	Zhang HY, Zhou W, Zhuang YB, Liang XM, Liu T. Draft genome sequence of Streptomyces bottropensis ATCC 25435, a bottromycin-producing actinomycete. Genome Announc, 2013, 1(2): e0001913. pmid: 23516178
[77]	Krawczyk JM, Völler GH, Krawczyk B, Kretz J, Brönstrup M, Süssmuth RD. Heterologous expression and engineering studies of labyrinthopeptins, class III lantibiotics from Actinomadura namibiensis. Chem Biol, 2013, 20(1): 111-122. pmid: 23352145
[78]	Shima J, Hesketh A, Okamoto S, Kawamoto S, Ochi K. Induction of actinorhodin production by rpsL (encoding ribosomal protein S12) mutations that confer streptomycin resistance in Streptomyces lividans and Streptomyces coelicolor A3(2). J Bacteriol, 1996, 178(24): 7276-7284. pmid: 8955413
[79]	Martinez A, Kolvek SJ, Yip CLT, Hopke J, Brown KA, Macneil IA, Osburne MS. Genetically modified bacterial strains and novel bacterial artificial chromosome shuttle vectors for constructing environmental libraries and detecting heterologous natural products in multiple expression hosts. Appl Environ Microbiol, 2004, 70(4): 2452-2463. pmid: 15066844
[80]	Jiang Z. Construction of Streptomycete secretion type expression vectors and development of Streptomyces chassis[Dissertation]. Huazhong Agricultural University, 2020.
	江洲. 链霉菌分泌型表达载体的构建及底盘细胞的改造[学位论文]. 华中农业大学, 2020.
[81]	Zhang D. Construction of Streptomyces roseosporus chassis cell with high level of cofactors based on CRISPR system and proteomics dissection strategy[Dissertation]. Sichuan University, 2021.
	张丹. 基于CRISPR系统和蛋白质组学策略构建高水平辅因子的玫瑰孢链霉菌底盘细胞[学位论文]. 四川大学, 2021.
[82]	Zhu YF, Zheng GF, Xin XJ, Ma JY, Ju JH, An FL. Combinatorial strategies for production improvement of anti-tuberculosis antibiotics ilamycins E₁/E₂ from deep sea-derived Streptomyces atratus SCSIO ZH16 ΔilaR. Bioresour Bioprocess, 2022, 9(1): 111. pmid: 38647771
[83]	Yang ZJ, Liu CY, Wang YY, Chen YY, Li QL, Zhang Y, Chen Q, Ju JH, Ma JY. MGCEP 1.0: a genetic-engineered marine-derived chassis cell for a scaled heterologous expression platform of microbial bioactive metabolites. ACS Synth Biol, 2022, 11(11): 3772-3784. pmid: 36241611

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菌株	底盘	野生型(Mb)	敲除大小(Mb)	底盘细胞基因组(Mb)	比例(%)	参考文献
阿维链霉菌(S. avermitilis)	SUK3	9.02	1.51	7.53	16.74	[56]
阿维链霉菌(S. avermitilis)	SUK17	9.02	1.67	7.35	18.51	[56]
天蓝色链霉菌(S. coelicolor)	ZM12	8.66	1.22	7.44	14.08	[25]
	M1146	8.66	0.17	8.49	1.96	[57]
	M1152	8.66	0.17	8.49	1.96	[57]
	M1154	8.66	0.17	8.49	1.96	[57]
白色链霉菌(S. albus)	Del14	6.80	0.50	6.33	7.35	[58]
变铅链霉菌(S. lividans)	ΔYA11	8.34	0.23	8.11	2.75	[59]

链霉菌较小基因组构建的研究进展

Progress on the construction of Streptomyces minimized genomes

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[1]	吴雪昌，汪志芸，周婕，朱旭芬，钱凯先. 提高产抗生素链霉菌紫外诱变正变率的研究[J]. 遗传, 2004, 26(4): 499-504.
[2]	邓子新，周秀芬. 质粒在大肠杆菌和链霉菌和FR-008之间的属间接合转移[J]. 遗传, 1994, 16(6): 7-10.