Progress in mammalian chromosome engineering

doi:10.12211/2096-8280.2022-072

Abstract

Abstract:

Mammalian chromosome engineering refers to its editing through various methods to create animal models for chromosome diseases, pharmaceutical factories of human proteins, dissection of mechanism underlying evolution, and even synthetic life. In recent years, some milestone technologies of mammalian chromosome engineering, such as natural chromosome modifications, chromosome design and synthesis, and chromosome large fragment transfer, have been developed and integrated with each other. At the same time, embryonic stem cells have also been developed as a new chassis for mammalian synthetic biology. Applications of embryonic stem cells to synthetic biology greatly promote the development of mammalian chromosome engineering, giving birth to a large number of animal models for studies on diseases and evolution, including mouse models for Down syndrome, mice producing human monoclonal antibodies, and chromosome-ligation mice to study the biological effects of chromosome recombination. However, the manipulations of mammalian chromosomes are still challenging due to the lack of comprehensive understanding on chromosome composition and mammalian development. In addition to technological challenges, there are issues with bioethics and bio-safety. In this review, we review main technologies and current applications of mammalian chromosome engineering, and we also highlight future applications and challenges of mammalian chromosome engineering.

Key words: chromosome engineering, chromosome modification, chromosome synthesis, chromosome transfer, synthetic biology, chromosome disease, embryonic stem cells

摘要：

关键词: 染色体工程, 染色体改造, 染色体合成, 染色体转移, 合成生物学, 染色体疾病, 胚胎干细胞

CLC Number:

ZHU Liyu, ZHAO Yulong, LI Wei, WANG Libin. Progress in mammalian chromosome engineering[J]. Synthetic Biology Journal, 2023, 4(2): 394-406.

朱骊宇, 赵玉龙, 李伟, 王立宾. 哺乳动物染色体工程研究进展[J]. 合成生物学, 2023, 4(2): 394-406.

Figures/Tables 1

References 95

1	徐赫鸣, 谢泽雄, 刘夺, 等. 酿酒酵母染色体设计与合成研究进展[J]. 遗传, 2017, 39(10): 865-876.
	XU H M, XIE Z X, LIU D, et al. Design and synthesis of yeast chromosomes[J]. Hereditas, 2017, 39(10): 865-876.
2	米福贵, 云锦凤, 逯晓萍. 植物染色体工程与育种[J]. 中国草地, 1999, 21(2): 64-67, 78.
	MI F G, YUN J F, LU X P. Chromosomal engineering and plant breeding[J]. Grassland of China, 1999, 21(2): 64-67, 78.
3	李炳林, 李宏运, 安泽伟, 等. 棉花染色体工程育种[J]. 山西农业大学学报, 2001, 21(1): 1-6.
	LI B L, LI H Y, AN Z W, et al. Cotton chromosome engineering breeding[J]. Journal of Shanxi Agricultural University, 2001, 21(1): 1-6.
4	纪军. 染色体工程改良小麦品质的研究[D]. 石家庄: 中国科学院石家庄农业现代化研究所, 2001.
	JI J. Study on improving wheat quality by chromosome engineering[D]. Shijiazhuang: Shijiazhuang Institute of Agricultural Modernization, Chinese Academy of Sciences, 2001.
5	丁明珠, 李炳志, 王颖, 等. 合成生物学重要研究方向进展[J]. 合成生物学, 2020, 1(1): 7-28.
	DING M Z, LI B Z, WANG Y, et al. Significant research progress in synthetic biology[J]. Synthetic Biology Journal, 2020, 1(1): 7-28.
6	STRICKLETT P K, NELSON R D, KOHAN D E. Site-specific recombination using an epitope tagged bacteriophage P1 Cre recombinase[J]. Gene, 1998, 215(2): 415-423.
7	RAMIREZ-SOLIS R, LIU P T, BRADLEY A. Chromosome engineering in mice[J]. Nature, 1995, 378(6558): 720-724.
8	ZHENG B H, SAGE M, CAI W W, et al. Engineering a mouse balancer chromosome[J]. Nature Genetics, 1999, 22(4): 375-378.
9	SU H, WANG X Z, BRADLEY A. Nested chromosomal deletions induced with retroviral vectors in mice[J]. Nature Genetics, 2000, 24(1): 92-95.
10	BITINAITE J, WAH D A, AGGARWAL A K, et al. FokI dimerization is required for DNA cleavage[J]. Proceedings of the National Academy of Sciences of the United States of America, 1998, 95(18): 10570-10575.
11	LAM K N, VAN BAKEL H, COTE A G, et al. Sequence specificity is obtained from the majority of modular C₂H₂ zinc-finger arrays[J]. Nucleic Acids Research, 2011, 39(11): 4680-4690.
12	UL AIN Q, CHUNG J Y, KIM Y H. Current and future delivery systems for engineered nucleases: ZFN, TALEN and RGEN[J]. Journal of Controlled Release, 2015, 205: 120-127.
13	KAZUKI Y, YAKURA Y, ABE S, et al. Down syndrome-associated haematopoiesis abnormalities created by chromosome transfer and genome editing technologies[J]. Scientific Reports, 2014, 4: 6136.
14	MAK A N S, BRADLEY P, CERNADAS R A, et al. The crystal structure of TAL effector PthXo1 bound to its DNA target[J]. Science, 2012, 335(6069): 716-719.
15	HOCKEMEYER D, WANG H Y, KIANI S, et al. Genetic engineering of human pluripotent cells using TALE nucleases[J]. Nature Biotechnology, 2011, 29(8): 731-734.
16	MA S Y, ZHANG S L, WANG F, et al. Highly efficient and specific genome editing in silkworm using custom TALENs[J]. PLoS One, 2012, 7(9): e45035.
17	BARRANGOU R, FREMAUX C, DEVEAU H, et al. CRISPR provides acquired resistance against viruses in prokaryotes[J]. Science, 2007, 315(5819): 1709-1712.
18	JINEK M, CHYLINSKI K, FONFARA I, et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity[J]. Science, 2012, 337(6096): 816-821.
19	ZUO E W, HUO X N, YAO X, et al. CRISPR/Cas9-mediated targeted chromosome elimination[J]. Genome Biology, 2017, 18(1): 224.
20	SHAO Y Y, LU N, WU Z F, et al. Creating a functional single-chromosome yeast[J]. Nature, 2018, 560(7718): 331-335.
21	WANG L B, LI Z K, WANG L Y, et al. A sustainable mouse karyotype created by programmed chromosome fusion[J]. Science, 2022, 377(6609): 967-975.
22	ZHANG X M, YAN M, YANG Z H, et al. Creation of artificial karyotypes in mice reveals robustness of genome organization[J]. Cell Research, 2022, 32(11): 1026-1029.
23	WANG Y A, QU Z, FANG Y, et al. Chromosome territory reorganization through artificial chromosome fusion is compatible with cell fate determination and mouse development[J]. Cell Discovery, 2023, 9: 11.
24	KOMOR A C, KIM Y B, PACKER M S, et al. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage[J]. Nature, 2016, 533(7603): 420-424.
25	ANZALONE A V, RANDOLPH P B, DAVIS J R, et al. Search-and-replace genome editing without double-strand breaks or donor DNA[J]. Nature, 2019, 576(7785): 149-157.
26	王会, 戴俊彪, 罗周卿. 基因组的“读-改-写"技术[J]. 合成生物学, 2020, 1(5): 503-515.
	WANG H, DAI J B, LUO Z Q. Reading, editing, and writing techniques for genome research[J]. Synthetic Biology Journal, 2020, 1(5): 503-515.
27	KOLISIS N, KOLISIS F. Synthetic biology: old and new dilemmas-the case of artificial life[J]. Biotech, 2021, 10(3): 16.
28	何博, 付宗恒, 吴毅, 等. 哺乳动物合成基因组学研究进展[J]. 合成生物学, 2022, 3(1): 78-97.
	HE B, FU Z H, WU Y, et al. Research progress of synthetic mammalian genomics[J]. Synthetic Biology Journal, 2022, 3(1): 78-97.
29	HUTCHISON C A, CHUANG R Y, NOSKOV V N, et al. Design and synthesis of a minimal bacterial genome[J]. Science, 2016, 351(6280): aad6253.
30	HOSHIKA S, LEAL N A, KIM M J, et al. Hachimoji DNA and RNA: a genetic system with eight building blocks[J]. Science, 2019, 363(6429): 884-887.
31	OSTROV N, LANDON M, GUELL M, et al. Design, synthesis, and testing toward a 57-codon genome[J]. Science, 2016, 353(6301): 819-822.
32	HOCHREIN L, MITCHELL L A, SCHULZ K, et al. L-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast[J]. Nature Communications, 2018, 9: 1931.
33	AGARWAL K L, BÜCHI H, CARUTHERS M H, et al. Total synthesis of the gene for an alanine transfer ribonucleic acid from yeast[J]. Nature, 1970, 227(5253): 27-34.
34	CELLO J, PAUL A V, WIMMER E. Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template[J]. Science, 2002, 297(5583): 1016-1018.
35	CHAN L Y, KOSURI S, ENDY D. Refactoring bacteriophage T7[J]. Molecular Systems Biology, 2005, 1: 2005.0018.
36	DORMITZER P R, SUPHAPHIPHAT P, GIBSON D G, et al. Synthetic generation of influenza vaccine viruses for rapid response to pandemics[J]. Science Translational Medicine, 2013, 5(185): 185ra68.
37	OLDFIELD L M, GRZESIK P, VOORHIES A A, et al. Genome-wide engineering of an infectious clone of herpes simplex virus type 1 using synthetic genomics assembly methods[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(42): E8885-E8894.
38	NOYCE R S, LEDERMAN S, EVANS D H. Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments[J]. PLoS One, 2018, 13(1): e0188453.
39	GIBSON D G, BENDERS G A, ANDREWS-PFANNKOCH C, et al. Complete chemical synthesis, assembly, and cloning of a mycoplasma genitalium genome[J]. Science, 2008, 319(5867): 1215-1220.
40	GIBSON D G, GLASS J I, LARTIGUE C, et al. Creation of a bacterial cell controlled by a chemically synthesized genome[J]. Science, 2010, 329(5987): 52-56.
41	FREDENS J, WANG K H, DE LA TORRE D, et al. Total synthesis of Escherichia coli with a recoded genome[J]. Nature, 2019, 569(7757): 514-518.
42	DYMOND J S, RICHARDSON S M, COOMBES C E, et al. Synthetic chromosome arms function in yeast and generate phenotypic diversity by design[J]. Nature, 2011, 477(7365): 471-476.
43	MITCHELL L A, WANG A, STRACQUADANIO G, et al. Synthesis, debugging, and effects of synthetic chromosome consolidation: synⅥ and beyond[J]. Science, 2017, 355(6329): eaaf4831.
44	SHEN Y, WANG Y, CHEN T, et al. Deep functional analysis of synⅡ, a 770-kilobase synthetic yeast chromosome[J]. Science, 2017, 355(6329): eaaf4791.
45	ANNALURU N, MULLER H, MITCHELL L A, et al. Total synthesis of a functional designer eukaryotic chromosome[J]. Science, 2014, 344(6179): 55-58.
46	WU Y, LI B Z, ZHAO M, et al. Bug mapping and fitness testing of chemically synthesized chromosome X[J]. Science, 2017, 355(6329): eaaf4706.
47	XIE Z X, LI B Z, MITCHELL L A, et al. "Perfect" designer chromosome Ⅴ and behavior of a ring derivative[J]. Science, 2017, 355(6329): eaaf4704.
48	ZHANG W M, ZHAO G H, LUO Z Q, et al. Engineering the ribosomal DNA in a megabase synthetic chromosome[J]. Science, 2017, 355(6329): eaaf3981.
49	LIU W, LUO Z Q, WANG Y, et al. Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods[J]. Nature Communications, 2018, 9: 1936.
50	JIA B, WU Y, LI B Z, et al. Precise control of SCRaMbLE in synthetic haploid and diploid yeast[J]. Nature Communications, 2018, 9: 1933.
51	BOEKE J D, CHURCH G, HESSEL A, et al. GENOME ENGINEERING. the genome project-write[J]. Science, 2016, 353(6295): 126-127.
52	MICHELSON A M, TODD A R. Nucleotides part ⅩⅩⅩⅡ. Synthesis of a dithymidine dinucleotide containing a 3′,5′-internucleotidic linkage[J]. Journal of the Chemical Society (Resumed), 1955: 2632-2638.
53	BEAUCAGE S L, CARUTHERS M H. Cheminform abstract: deoxynucleoside phosphoramidites. a new class of key intermediates for deoxypolynucleotide synthesis[J/OL]. Chemischer Informationsdienst, 1981, 12(36)[2022-12-01]. .
54	FODOR S P, READ J L, PIRRUNG M C, et al. Light-directed, spatially addressable parallel chemical synthesis[J]. Science, 1991, 251(4995): 767-773.
55	SHETTY R P, ENDY D, KNIGHT T F. Engineering BioBrick vectors from BioBrick parts[J]. Journal of Biological Engineering, 2008, 2: 5.
56	ENGLER C, KANDZIA R, MARILLONNET S. A one pot, one step, precision cloning method with high throughput capability[J]. PLoS One, 2008, 3(11): e3647.
57	GIBSON D G, YOUNG L, CHUANG R Y, et al. Enzymatic assembly of DNA molecules up to several hundred kilobases[J]. Nature Methods, 2009, 6(5): 343-345.
58	ABREMSKI K, HOESS R. Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein[J]. The Journal of Biological Chemistry, 1984, 259(3): 1509-1514.
59	KUHSTOSS S, RAO R N. Analysis of the integration function of the streptomycete bacteriophage phi C31[J]. Journal of Molecular Biology, 1991, 222(4): 897-908.
60	FU J, BIAN X Y, HU S, et al. Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting[J]. Nature Biotechnology, 2012, 30(5): 440-446.
61	COBB R E, WANG Y J, ZHAO H M. High-efficiency multiplex genome editing of Streptomyces species using an engineered CRISPR/Cas system[J]. ACS Synthetic Biology, 2015, 4(6): 723-728.
62	ZHOU J T, WU R H, XUE X L, et al. CasHRA (Cas9-facilitated Homologous Recombination Assembly) method of constructing megabase-sized DNA[J]. Nucleic Acids Research, 2016, 44(14): e124.
63	MITCHELL L A, MCCULLOCH L H, PINGLAY S, et al. De novo assembly and delivery to mouse cells of a 101 kb functional human gene[J]. Genetics, 2021, 218(1): iyab038.
64	MONTOLIU L. Large-scale preparation of yeast agarose plugs to isolate yeast artificial chromosome DNA[J/OL]. Cold Spring Harbor Protocols, 2018, 2018(8)[2022-12-01]. .
65	GNIRKE A, HUXLEY C, PETERSON K, et al. Microinjection of intact 200- to 500-kb fragments of YAC DNA into mammalian cells[J]. Genomics, 1993, 15(3): 659-667.
66	KIM J Y, CHOI J H, KIM S H, et al. Efficacy of gene modification in placenta-derived mesenchymal stem cells based on nonviral electroporation[J]. International Journal of Stem Cells, 2021, 14(1): 112-118.
67	STEWART M P, LANGER R, JENSEN K F. Intracellular delivery by membrane disruption: mechanisms, strategies, and concepts[J]. Chemical Reviews, 2018, 118(16): 7409-7531.
68	MARSCHALL P, MALIK N, LARIN Z. Transfer of YACs up to 2.3 Mb intact into human cells with polyethylenimine[J]. Gene Therapy, 1999, 6(9): 1634-1637.
69	MEJÍA J E, WILLMOTT A, LEVY E, et al. Functional complementation of a genetic deficiency with human artificial chromosomes[J]. American Journal of Human Genetics, 2001, 69(2): 315-326.
70	LARTIGUE C, GLASS J I, ALPEROVICH N, et al. Genome transplantation in bacteria: changing one species to another[J]. Science, 2007, 317(5838): 632-638.
71	SUZUKI T, KAZUKI Y, HARA T, et al. Current advances in microcell-mediated chromosome transfer technology and its applications[J]. Experimental Cell Research, 2020, 390(1): 111915.
72	SINENKO S A, PONOMARTSEV S V, TOMILIN A N. Human artificial chromosomes for pluripotent stem cell-based tissue replacement therapy[J]. Experimental Cell Research, 2020, 389(1): 111882.
73	BROWN D M, CHAN Y A, DESAI P J, et al. Efficient size-independent chromosome delivery from yeast to cultured cell lines[J]. Nucleic Acids Research, 2017, 45(7): e50.
74	KUGOH H, MITSUYA K, MEGURO M, et al. Mouse A9 cells containing single human chromosomes for analysis of genomic imprinting[J]. DNA Research, 1999, 6(3): 165-172.
75	O'DOHERTY A, RUF S, MULLIGAN C, et al. An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes[J]. Science, 2005, 309(5743): 2033-2037
76	WADE-MARTINS R, SMITH E R, TYMINSKI E, et al. An infectious transfer and expression system for genomic DNA loci in human and mouse cells[J]. Nature Biotechnology, 2001, 19(11): 1067-1070.
77	MORALLI D, MONACO Z L. Developing de novo human artificial chromosomes in embryonic stem cells using HSV-1 amplicon technology[J]. Chromosome Research, 2015, 23(1): 105-110.
78	LI L P, BLANKENSTEIN T. Generation of transgenic mice with megabase-sized human yeast artificial chromosomes by yeast spheroplast-embryonic stem cell fusion[J]. Nature Protocols, 2013, 8(8): 1567-1582.
79	LISKOVYKH M, LEE N C, LARIONOV V, et al. Moving toward a higher efficiency of microcell-mediated chromosome transfer[J]. Molecular Therapy-Methods & Clinical Development, 2016, 3: 16043.
80	FEUK L, CARSON A R, SCHERER S W. Structural variation in the human genome[J]. Nature Reviews Genetics, 2006, 7(2): 85-97.
81	HASTINGS P J, LUPSKI J R, ROSENBERG S M, et al. Mechanisms of change in gene copy number[J]. Nature Reviews Genetics, 2009, 10(8): 551-564.
82	MAYNARD T M, HASKELL G T, LIEBERMAN J A, et al. 22q11 DS: genomic mechanisms and gene function in DiGeorge/velocardiofacial syndrome[J]. International Journal of Developmental Neuroscience, 2002, 20(3/4/5): 407-419.
83	WU Q F, NIEBUHR E, YANG H M, et al. Determination of the 'critical region' for cat-like cry of Cri-du-chat syndrome and analysis of candidate genes by quantitative PCR[J]. European Journal of Human Genetics, 2005, 13(4): 475-485.
84	SHINOHARA T, TOMIZUKA K, MIYABARA S, et al. Mice containing a human chromosome 21 model behavioral impairment and cardiac anomalies of Down's syndrome[J]. Human Molecular Genetics, 2001, 10(11): 1163-1175.
85	RICARD G, MOLINA J, CHRAST J, et al. Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models[J]. PLoS Biology, 2010, 8(11): e1000543.
86	TUNÇ E, ILGAZ S. Robertsonian translocation (13;14) and its clinical manifestations: a literature review[J]. Reproductive Biomedicine Online, 2022, 45(3): 563-573.
87	YUNIS J J, PRAKASH O. The origin of man: a chromosomal pictorial legacy[J]. Science, 1982, 215(4539): 1525-1530.
88	MATSUMURA H, TADA M, OTSUJI T, et al. Targeted chromosome elimination from ES-somatic hybrid cells[J]. Nature Methods, 2007, 4(1): 23-25.
89	LI L B, CHANG K H, WANG P R, et al. Trisomy correction in down syndrome induced pluripotent stem cells[J]. Cell Stem Cell, 2012, 11(5): 615-619.
90	TOMIZUKA K, YOSHIDA H, UEJIMA H, et al. Functional expression and germline atransmission of a human chromosome fragment in chimaeric mice[J]. Nature Genetics, 1997, 16(2): 133-143.
91	TOMIZUKA K, SHINOHARA T, YOSHIDA H, et al. Double trans-chromosomic mice: maintenance of two individual human chromosome fragments containing Ig heavy and kappa loci and expression of fully human antibodies[J]. Proceedings of the National Academy of Sciences of the United States of America, 2000, 97(2): 722-727.
92	KUROIWA Y, KASINATHAN P, SATHIYASEELAN T, et al. Antigen-specific human polyclonal antibodies from hyperimmunized cattle[J]. Nature Biotechnology, 2009, 27(2): 173-181.
93	KAZUKI Y, KOBAYASHI K, AUEVIRIYAVIT S, et al. Trans-chromosomic mice containing a human CYP3A cluster for prediction of xenobiotic metabolism in humans[J]. Human Molecular Genetics, 2013, 22(3): 578-592.
94	KOBAYASHI K, ABE C, ENDO M, et al. Gender difference of hepatic and intestinal CYP3A4 in CYP3A humanized mice generated by a human chromosome-engineering technique[J]. Drug Metabolism Letters, 2017, 11(1): 60-67.
95	KAZUKI Y, KOBAYASHI K, HIRABAYASHI M, et al. Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism[J]. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(8): 3072-3081.

[1]	GAO Ge, BIAN Qi, WANG Baojun. Synthetic genetic circuit engineering: principles, advances and prospects [J]. Synthetic Biology Journal, 2025, 6(1): 45-64.
[2]	LI Jiyuan, WU Guosheng. Two hypothesises for the origins of organisms from the synthetic biology perspective [J]. Synthetic Biology Journal, 2025, 6(1): 190-202.
[3]	JIAO Hongtao, QI Meng, SHAO Bin, JIANG Jinsong. Legal issues for the storage of DNA data [J]. Synthetic Biology Journal, 2025, 6(1): 177-189.
[4]	TANG Xinghua, LU Qianneng, HU Yilin. Philosophical reflections on synthetic biology in the Anthropocene [J]. Synthetic Biology Journal, 2025, 6(1): 203-212.
[5]	XU Huaisheng, SHI Xiaolong, LIU Xiaoguang, XU Miaomiao. Key technologies for DNA storage: encoding, error correction, random access, and security [J]. Synthetic Biology Journal, 2025, 6(1): 157-176.
[6]	SHI Ting, SONG Zhan, SONG Shiyi, ZHANG Yi-Heng P. Job. In vitro BioTransformation (ivBT): a new frontier of industrial biomanufacturing [J]. Synthetic Biology Journal, 2024, 5(6): 1437-1460.
[7]	CHAI Meng, WANG Fengqing, WEI Dongzhi. Synthesis of organic acids from lignocellulose by biotransformation [J]. Synthetic Biology Journal, 2024, 5(6): 1242-1263.
[8]	SHAO Mingwei, SUN Simian, YANG Shimao, CHEN Guoqiang. Bioproduction based on extremophiles [J]. Synthetic Biology Journal, 2024, 5(6): 1419-1436.
[9]	CHEN Yu, ZHANG Kang, QIU Yijing, CHENG Caiyun, YIN Jingjing, SONG Tianshun, XIE Jingjing. Progress of microbial electrosynthesis for conversion of CO₂ [J]. Synthetic Biology Journal, 2024, 5(5): 1142-1168.
[10]	ZHENG Haotian, LI Chaofeng, LIU Liangxu, WANG Jiawei, LI Hengrun, NI Jun. Design, optimization and application of synthetic carbon-negative phototrophic community [J]. Synthetic Biology Journal, 2024, 5(5): 1189-1210.
[11]	CHEN Ziling, XIANG Yangfei. Integrated development of organoid technology and synthetic biology [J]. Synthetic Biology Journal, 2024, 5(4): 795-812.
[12]	CAI Bingyu, TAN Xiangtian, LI Wei. Advances in synthetic biology for engineering stem cell [J]. Synthetic Biology Journal, 2024, 5(4): 782-794.
[13]	XIE Huang, ZHENG Yilei, SU Yiting, RUAN Jingyi, LI Yongquan. An overview on reconstructing the biosynthetic system of actinomycetes for polyketides production [J]. Synthetic Biology Journal, 2024, 5(3): 612-630.
[14]	ZHA Wenlong, BU Lan, ZI Jiachen. Advances in synthetic biology for producing potent pharmaceutical ingredients of traditional Chinese medicine [J]. Synthetic Biology Journal, 2024, 5(3): 631-657.
[15]	HUI Zhen, TANG Xiaoyu. Applications of the CRISPR/Cas9 editing system in the study of microbial natural products [J]. Synthetic Biology Journal, 2024, 5(3): 658-671.