Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2022, Vol. 42 Issue (12): 12-26    DOI: 10.13523/j.cb.2204077
研究报告     
Pmr1基因缺失对粟酒裂殖酵母细胞有性生殖和有丝分裂的影响及其分子机制研究*
叶姿妤1,丁祥2,鲁艳1,周丽倩1,刘欣岚2,蒲帝宏1,侯怡铃1,**()
1 西华师范大学生命科学学院 西南野生动植物资源保护教育部重点实验室 南充 637009
2 西华师范大学环境科学与工程学院 南充 637009
Effects of pmr1 Gene Deletion on Sexual Reproduction and Mitosis of Fission Yeast Cells and Its Molecular Mechanism
YE Zi-yu1,DING Xiang2,LU Yan1,ZHOU Li-qian1,LIU Xin-lan2,PU Di-hong1,HOU Yi-ling1,**()
1 Key Laboratory of Southwest China Wildlife Resource Conservation (Ministry of Education), College of Life Science, China West Normal University, Nanchong 637009, China
2 College of Environmental Science and Engineering, China West Normal University, Nanchong 637009, China
 全文: PDF(3140 KB)   HTML
摘要：

目的:pmr1基因编码P型钙转运ATP酶Pmr1,参与维持细胞壁完整性和调控胞质分裂。以粟酒裂殖酵母为模式细胞,探究pmr1缺失后对细胞有性生殖及细胞分裂中肌动蛋白环精细动力学的影响,揭示pmr1缺失后细胞异常生长过程中的关键基因和代谢通路。方法:通过细胞生长速率测定、产孢统计、绿色荧光蛋白标记肌动蛋白和活细胞成像的方法,检测pmr1缺失对细胞有丝分裂和有性生殖的影响;采用RNA-Seq对野生型菌株和pmr1Δ菌株测序和生物信息学分析,并进行qRT-PCR验证。结果:pmr1缺失后细胞生长减慢,分裂期细胞长度减小,子囊孢子长度增加,且肌动蛋白环的形成时间增加。RNA测序结果显示,mfm1、mfm2和mat1-Mc下调,错配修复通路cdc1和exo1上调以及糖酵解/糖异生途径pgi1、pfk1和dld1下调是引起pmr1Δ孢子长度增加的主要因素;糖酵解/糖异生途径tdh1、pgk1下调,以及脂肪酸合成代谢途径fas1、fas2、cut6和lcf1下调导致了pmr1Δ分裂期细胞长度减小;hsp9上调是影响pmr1Δ收缩环形成时间增加的关键基因。qRT-PCR实验证实,pmr1缺失后关键基因的表达趋势与RNA-Seq结果一致。结论:pmr1缺失后,粟酒裂殖酵母细胞中错配修复通路、糖酵解/糖异生途径及脂肪酸合成代谢途径发生障碍,导致细胞及孢子形态均异常,且肌动蛋白环形成受阻,细胞增殖减缓。
关键词： pmr1基因;  裂殖酵母;  细胞分裂;  RNA-Seq测序;  代谢通路    
Abstract:

Objective: The pmr1 gene encodes P-type calcium-transporting ATPase Pmr1, which is involved in maintaining cell wall integrity and regulating cytokinesis. In this study, fission yeast was used as a model cell to explore the effects of pmr1 deletion on the sexual reproduction and dynamics of actin rings during cell mitosis, and to reveal the key genes and metabolic pathways of abnormal cell mitosis after pmr1 deletion. Methods: The effects of pmr1 deletion on cell mitosis and sexual reproduction were detected by cell growth rate measurement, spore production observation and statistics, green fluorescent protein-labeled monitoring and living cell imaging; The wild-type and pmr1Δ strain were sequenced by RNA-Seq and analyzed by bioinformatics, and verified by qRT-PCR. Results: The pmr1 deletion could slow down cell growth, decrease cell length in mitosis, increase length of sexually reproductive ascospore, and increase formation time of actin ring. RNA-sequencing results revealed that down-regulation of mfm1, mfm2 and mat1-Mc, up-regulation of cdc1 and exo1 in the mismatch repair pathway, and down-regulation of pgi1, pfk1 and dld1 in the glycolysis/gluconeogenesis pathway are the main factor of the increased spore length in the pmr1Δ; Meanwhile, the down-regulation of tdh1 and pgk1 in the glycolysis/gluconeogenesis pathway and the down-regulation of fas1, fas2, cut6 and lcf1 in the fatty acid anabolic pathway also led to the decreased cell length in mitosis of pmr1Δ; The up-regulation of hsp9 is the key gene that affected the formation time of actin ring in pmr1Δ. qRT-PCR experiments confirmed that the expression trends of key genes after pmr1 deletion were consistent with the RNA-Seq results. Conclusion: After pmr1 deletion, the mismatch repair pathway, glycolysis/gluconeogenesis pathway and fatty acid anabolic pathway are hindered in fission yeast cells, resulting in abnormal cell and spore morphology, obstruction of actin ring formation, and slowing down of cell proliferation.
Key words: pmr1 gene    Fission yeast    Cell division    RNA-Seq    Metabolic pathway
收稿日期: 2022-04-29 出版日期: 2023-01-05
ZTFLH:  Q932  
基金资助: *四川省科技厅应用基础研究(2022NSFSC0107);四川省科技厅科技成果转化项目资助项目(2022NZZJ0003)
通讯作者: 侯怡铃     E-mail: starthlh@126.com
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
叶姿妤
丁祥
鲁艳
周丽倩
刘欣岚
蒲帝宏
侯怡铃

引用本文:

叶姿妤,丁祥,鲁艳,周丽倩,刘欣岚,蒲帝宏,侯怡铃. Pmr1基因缺失对粟酒裂殖酵母细胞有性生殖和有丝分裂的影响及其分子机制研究*[J]. 中国生物工程杂志, 2022, 42(12): 12-26.

YE Zi-yu,DING Xiang,LU Yan,ZHOU Li-qian,LIU Xin-lan,PU Di-hong,HOU Yi-ling. Effects of pmr1 Gene Deletion on Sexual Reproduction and Mitosis of Fission Yeast Cells and Its Molecular Mechanism. China Biotechnology, 2022, 42(12): 12-26.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2204077    或    https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I12/12

图1  pmr1基因的基因位置、PMR1蛋白结构和蛋白保守域
Strains Genotype
PT.286 h- wt
PT.287 h+ wt
PT.3850 h+ wt: Pact1-LifeAct-mGFP: LEU1
22 h- pmr1Δ: kanR
22B h? pmr1Δ: Pact1-LifeAct-mGFP: LEU1
表1  实验所用菌株及编号
图2  25℃下pmr1基因缺失对细胞生长和产孢的影响
图3  pmr1基因缺失对细胞长度和肌动蛋白环定位的影响
图4  pmr1基因缺失对肌动蛋白环形成时间、收缩时间及收缩速率的影响
Sample Clean reads Clean bases Error rate Q30 / % GC content
wt_1 46 447 832 6.97 G 0.02 94.57 41.43
wt_2 45 173 776 6.78 G 0.02 95.09 41.41
wt_3 44 388 600 6.66 G 0.03 94.11 41.23
pmr1_1 41 279 024 6.19 G 0.02 95.31 41.27
pmr1_2 41 845 000 6.28 G 0.02 95.46 41.35
pmr1_3 44 284 874 6.64 G 0.02 94.81 40.94
表2  转录组测序数据质量统计
Gene name FPKM(wt) FPKM(pmr1Δ) Gene description
gpd3 15 353.453 88 15 959.829 08 Glyceraldehyde 3-phosphate dehydrogenase Gpd3
zym1 13 760.905 16 14 307.039 34 Metallothionein Zym1
hsp9 7 879.472 53 8 560.037 92 Heat shock protein Hsp9
hsp16 6 429.324 40 6 194.116 955 Heat shock protein Hsp16
eno101 5 927.174 232 6 461.217 911 Enolase
fba1 6 012.452 647 5 818.516 153 Fructose-bisphosphate aldolase Fba1
tdh1 5 679.168 434 4 102.244 391 Glyceraldehyde-3-phosphate dehydrogenase Tdh1
pgk1 4 919.322 538 3 933.365 814 Phosphoglycerate kinase Pgk1
tef103 4 107.470 752 3 890.983 788 Translation elongation factor EF-1 alpha Ef1a-c
gpm1 3 555.484 13 3 820.980 92 Monomeric 2, 3-bisphosphoglycerate (BPG)-dependent phosphoglycerate mutase (PGAM), Gpm1
pex7 3 358.379 28 3 569.658 727 Peroxin-7
pyk1 3 488.753 815 3 564.304 155 Pyruvate kinase
lsd90 3 488.525 293 2 542.280 536 Lsd90 protein
hry1 3 423.976 852 2 454.672 867 HHE domain cation binding protein
ole1 3 069.993 526 2 462.650 536 Acyl-CoA desaturase
表3  野生型和pmr1Δ菌株高表达基因统计 ( FPKM>3 000为极高表达)
Gene name Log2FoldChange Padj Gene description
mat2-Pc 12.589 4 4.48×10-24 Silenced P-specific polypeptide Pc
mat2-Pi 9.057 1 5.97×10-12 Silenced P-specific polypeptide Pi
Tf2-13 8.503 3 2.58×10-10 Retro transposable element/transposon Tf2-type
ftm4 5.942 7 2.68×10-168 S.pombe specific 5Tm protein family
gdt1 4.297 2 0.00 Human TMEM165 homolog, implicated in calcium transport
pdc102 4.157 6 8.62×10-5 Pyruvate decarboxylase
mat1-Mi 3.759 4 4.91×10-11 Mating-type M-specific polypeptide Mm/Mi
fub2 1.577 6 3.94×10-51 PI31 proteasome regulator Fub2
map3 1.503 9 4.23×10-20 Pheromone M-factor receptor Map3
mal1 1.45 7.07×10-96 Maltase alpha-glucosidase Mal1
prl24 1.326 4 3.44×10-6 Non-coding RNA, poly(A)-bearing
nam3 1.297 2 3.68×10-3 LncRNA nam3
cox1 1.277 9 5.69×10-4 Cytochrome C oxidase subunit 1
isp3 1.046 7 1.03×10-8 Spore wall structural constituent Isp3
表4  野生型和pmr1Δ菌株上调的差异表达基因(log2FoldChange≥ 1 )
Gene name Log2FoldChange Padj Gene description
mat3-Mc -6.721 4 3.54×10-5 Mating-type m-specific HMG-box transcription factor Mc at silenced MAT3 locus
mat1-Mc -5.202 4 1.50×10-2 Mating-type m-specific polypeptide Mc
mfm2 -4.271 2 0.00 M-factor precursor Mfm2
mfm1 -2.902 0 1.57×10-78 M-factor precursor Mfm1
mam1 -1.664 9 9.75×10-115 M-factor transmembrane transporter Mam1
ght3 -1.555 4 1.20×10-54 Hexose transmembrane transporter Ght3
cig2 -1.239 3 2.30×10-6 G1/S-specific B-type cyclin Cig2
hsp3103 -1.031 0 1.99×10-35 ThiJ domain protein
cta3 -1.005 0 1.06×10-5 P-type ATPase, potassium exporting Cta3
表5  野生型和pmr1Δ菌株下调的差异表达基因(log2FoldChange≤ -1)
图5  差异表达基因火山图
图6  差异表达基因的GO富集
图7  差异表达基因的KEGG富集
图8  差异表达基因的代谢通路富集
图9  关键差异表达基因qRT-PCR验证
[1] Rincon S A, Paoletti A. Molecular control of fission yeast cytokinesis. Seminars in Cell & Developmental Biology, 2016, 53: 28-38.
[2] Hayles J, Nurse P. Introduction to fission yeast as a model system. Cold Spring Harbor Protocols, 2018, 2018(5). DOI: 10.1101/pdb.top079749.
doi: 10.1101/pdb.top079749
[3] 战春君, 李翔, 刘国强, 等. 巴斯德毕赤酵母甘油转运体的发现及功能研究. 中国生物工程杂志, 2017, 37(7): 48-55.
Zhan C J, Li X, Liu G Q, et al. Identification of glycerol transporter in Pichia pastoris and function research. China Biotechnology, 2017, 37(7): 48-55.
[4] 谭秀梅, 丁祥, 袁荣美, 等. 线粒体膜蛋白mgr2基因的缺失导致裂殖酵母细胞动力学变化的研究. 基因组学与应用生物学, 2021, 40(S1): 2068-2075.
Tan X M, Ding X, Yuan R M, et al. The study of loss of mitochondrial membrane protein mgr 2 gene results in changes of cell dynamics in fission yeast. Genomics and Applied Biology, 2021, 40(S1): 2068-2075.
[5] Nakazawa N, Xu X Y, Arakawa O, et al. Coordinated roles of the putative ceramide-conjugation protein, Cwh43, and a Mn2+-transporting, P-type ATPase, Pmr1, in fission yeast. G3(Bethesda), 2019, 9(8): 2667-2676.
[6] Cortés J C G, Katoh-Fukui R, Moto K, et al. Schizosaccharomyces pombe Pmr1p is essential for cell wall integrity and is required for polarized cell growth and cytokinesis. Eukaryotic Cell, 2004, 3(5): 1124-1135.
doi: 10.1128/EC.3.5.1124-1135.2004
[7] Maeda T, Sugiura R, Kita A, et al. Pmr1, a P-type ATPase, and Pdt1, an Nramp homologue, cooperatively regulate cell morphogenesis in fission yeast: the importance of Mn2+ homeostasis. Genes to Cells, 2004, 9(1): 71-82.
doi: 10.1111/j.1356-9597.2004.00699.x
[8] Ma Y, Sugiura R, Koike A, et al. Transient receptor potential (TRP) and Cch1-Yam 8 channels play key roles in the regulation of cytoplasmic Ca2+ in fission yeast. PLoS One, 2011, 6(7): e22421.
doi: 10.1371/journal.pone.0022421
[9] Caetano C, Limbo O, Farmer S, et al. Tolerance of deregulated G1/S transcription depends on critical G1/S regulon genes to prevent catastrophic genome instability. Cell Reports, 2014, 9(6): 2279-2289.
doi: 10.1016/j.celrep.2014.11.039 pmid: 25533348
[10] Poddar A, Sidibe O, Ray A, et al. Calcium spikes accompany cleavage furrow ingression and cell separation during fission yeast cytokinesis. Molecular Biology of the Cell, 2021, 32(1): 15-27.
doi: 10.1091/mbc.E20-09-0609 pmid: 33175606
[11] Ryan C J, Roguev A, Patrick K, et al. Hierarchical modularity and the evolution of genetic interactomes across species. Molecular Cell, 2012, 46(5): 691-704.
doi: 10.1016/j.molcel.2012.05.028 pmid: 22681890
[12] Hu Z L, Bonifas J M, Beech J, et al. Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Nature Genetics, 2000, 24(1): 61-65.
pmid: 10615129
[13] Büttner S, Faes L, Reichelt W N, et al. The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca2+ levels to α-synuclein toxicity in Parkinson’s disease models. Cell Death & Differentiation, 2013, 20(3): 465-477.
[14] 房彦平, 季爱民, 杨月莲, 等. 沉默PMR1表达促进胰岛细胞分泌胰岛素的研究. 南方医科大学学报, 2009, 29(8): 1565-1567, 1570.
pmid: 19726293
Fang Y P, Ji A M, Yang Y L, et al. Plasma membrane-related Ca2+-ATPase-1 gene silencing promotes insulin secretion in islet β cells NIT. Journal of Southern Medical University, 2009, 29(8): 1565-1567, 1570.
pmid: 19726293
[15] 白鑫, 丁祥, 李慧, 等. alg3、vps1301、rad51基因缺失对粟酒裂殖酵母接合生殖的影响. 河北大学学报(自然科学版), 2021, 41(6): 720-727.
Bai X, Ding X, Li H, et al. Effects of the deletions of alg3, vps1301 and rad51 genes on the growth and conjugal reproduction of Schizosaccharomyces pombe. Journal of Hebei University (Natural Science Edition), 2021, 41(6): 720-727.
[16] 田宏.Wnt5a启动子甲基化可促进亚牛磺酸合成缺陷胶质瘤细胞侵袭. 沈阳: 中国医科大学, 2018.
Tian H.Hypomethylation of Wnt5a promoterincreased invasion ability of hypotaurine synthesis deficient glioma cells. Shenyang: China Medical University, 2018.
[17] 王芳平, 王志坚, 李永香. 三种模式微生物基因组中GC含量的比较. 基因组学与应用生物学, 2019, 38(5): 2215-2220.
Wang F P, Wang Z J, Li Y X. Comparison of GC contents in genomes of the three model microbes. Genomics and Applied Biology, 2019, 38(5): 2215-2220.
[18] Hayles J, Wood V, Jeffery L, et al. A genome-wide resource of cell cycle and cell shape genes of fission yeast. Open Biology, 2013, 3(5): 130053.
doi: 10.1098/rsob.130053
[19] Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Research, 2000, 28(1): 27-30.
doi: 10.1093/nar/28.1.27 pmid: 10592173
[20] van den Brink D M, Brites P, Haasjes J, et al. Identification of PEX7 as the second gene involved in refsum disease. The American Journal of Human Genetics, 2003, 72(2): 471-477.
doi: 10.1086/346093
[21] Jang Y J, Park S K, Yoo H S. Isolation of an HSP12-homologous gene of Schizosaccharomyces pombe suppressing a temperature-sensitive mutant allele of cdc4. Gene, 1996, 172(1): 125-129.
pmid: 8654972
[22] Duncan C D S, Rodríguez-López M, Ruis P, et al. General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(8): E 1829-E1838.
[23] Kim J Y, Kim E J, Lopez-Maury L, et al. A metabolic strategy to enhance long-term survival by Phx 1 through stationary phase-specific pyruvate decarboxylases in fission yeast. Aging, 2014, 6(7): 587-601.
doi: 10.18632/aging.100682
[24] Colinet A S, Sengottaiyan P, Deschamps A, et al. Yeast Gdt1 is a Golgi-localized calcium transporter required for stress-induced calcium signaling and protein glycosylation. Scientific Reports, 2016, 6: 24282.
doi: 10.1038/srep24282
[25] Kjaerulff S, Davey J, Nielsen O. Analysis of the structural genes encoding M-factor in the fission yeast Schizosaccharomyces pombe: identification of a third gene, mfm3. Molecular and Cellular Biology, 1994, 14(6): 3895-3905.
doi: 10.1128/mcb.14.6.3895-3905.1994 pmid: 8196631
[26] Graml V, Studera X, Lawson J L D, et al. A genomic multiprocess survey of machineries that control and link cell shape, microtubule organization, and cell-cycle progression. Developmental Cell, 2014, 31(2): 227-239.
doi: 10.1016/j.devcel.2014.09.005 pmid: 25373780
[27] Scotchman E, Kume K, Navarro F J, et al. Identification of mutants with increased variation in cell size at onset of mitosis in fission yeast. Journal of Cell Science, 2021, 134(3): jcs251769.
doi: 10.1242/jcs.251769
[28] Forsburg S L, Hodson J A. Mitotic replication initiation proteins are not required for pre-meiotic S phase. Nature Genetics, 2000, 25(3): 263-268.
doi: 10.1038/77015 pmid: 10888871
[29] Szankasi P, Smith G R. A role for exonuclease I from S. pombe in mutation avoidance and mismatch correction. Science, 1995, 267(5201): 1166-1169.
doi: 10.1126/science.7855597 pmid: 7855597
[30] Tran P T, Erdeniz N, Symington L S, et al. EXO1-A multi-tasking eukaryotic nuclease. DNA Repair, 2004, 3(12): 1549-1559.
pmid: 15474417
[31] Egel R, Beach D H, Klar A J. Genes required for initiation and resolution steps of mating-type switching in fission yeast. Proceedings of the National Academy of Sciences of the United States of America, 1984, 81(11): 3481-3485.
[32] Mansour A A, Tornier C, Lehmann E, et al. Control of GT repeat stability in Schizosaccharomyces pombe by mismatch repair factors. Genetics, 2001, 158(1): 77-85.
doi: 10.1093/genetics/158.1.77 pmid: 11333219
[33] Lee Y, Min K, Son H, et al. ELP3 is involved in sexual and asexual development, virulence, and the oxidative stress response in Fusarium graminearum. Molecular Plant-Microbe Interactions, 2014, 27(12): 1344-1355.
doi: 10.1094/MPMI-05-14-0145-R
[34] Xie M H, Ma N, Bai N, et al. Phospholipase C (AoPLC2) regulates mycelial development, trap morphogenesis, and pathogenicity of the nematode-trapping fungus Arthrobotrys oligospora. Journal of Applied Microbiology, 2022, 132(3): 2144-2156.
doi: 10.1111/jam.15370
[35] Qin Y L, Zhang S B, Lv Y Y, et al. Transcriptomics analyses and biochemical characterization of Aspergillus flavus spores exposed to 1-nonanol. Applied Microbiology and Biotechnology, 2022, 106(5-6): 2091-2106.
doi: 10.1007/s00253-022-11830-4
[36] Laplante M, Sabatini D M. mTOR signaling in growth control and disease. Cell, 2012, 149(2): 274-293.
doi: 10.1016/j.cell.2012.03.017 pmid: 22500797
[37] Willet A H, DeWitt A K, Beckley J R, et al. NDR kinase Sid2 drives anillin-like Mid1 from the membrane to promote cytokinesis and medial division site placement. Current Biology, 2019, 29(6): 1055-1063, e2.
doi: S0960-9822(19)30134-4 pmid: 30853434
[38] Schmoller K M, Turner J J, Kõivomägi M, et al. Dilution of the cell cycle inhibitor Whi 5 controls budding-yeast cell size. Nature, 2015, 526(7572): 268-272.
doi: 10.1038/nature14908
[39] Li Y J, Christensen J R, Homa K E, et al. The F-actin bundler α-actinin Ain 1 is tailored for ring assembly and constriction during cytokinesis in fission yeast. Molecular Biology of the Cell, 2016, 27(11): 1821-1833.
doi: 10.1091/mbc.e16-01-0010
[40] Kovar D R, Wu J Q, Pollard T D. Profilin-mediated competition between capping protein and formin Cdc12p during cytokinesis in fission yeast. Molecular Biology of the Cell, 2005, 16(5): 2313-2324.
pmid: 15743909
[41] Chatfield-Reed K, Vachon L, Kwon E J G, et al. Conserved and diverged functions of the calcineurin-activated Prz 1 transcription factor in fission yeast. Genetics, 2016, 202(4): 1365-1375.
doi: 10.1534/genetics.115.184218 pmid: 26896331
[42] You D, Wang M M, Ye B C. Acetyl-CoA synthetases of Saccharopolyspora erythraea are regulated by the nitrogen response regulator GlnR at both transcriptional and post-translational levels. Molecular Microbiology, 2017, 103(5): 845-859.
doi: 10.1111/mmi.13595 pmid: 27987242
[43] Gresh L, Bourachot B, Reimann A, et al. The SWI/SNF chromatin-remodeling complex subunit SNF 5 is essential for hepatocyte differentiation. The EMBO Journal, 2005, 24(18): 3313-3324.
doi: 10.1038/sj.emboj.7600802
[44] Martinez-Moya P, Campusano S, Córdova P, et al. Convergence between regulation of carbon utilization and catabolic repression in Xanthophyllomyces dendrorhous. mSphere, 2020, 5(2): e00065-e00020.
[45] Lim P J, Marfurt S, Lindert U, et al. Omics profiling of S2P mutant fibroblasts as a mean to unravel the pathomechanism and molecular signatures of X-linked MBTPS 2 osteogenesis imperfecta. Frontiers in Genetics, 2021, 12: 662751.
doi: 10.3389/fgene.2021.662751
[46] Alexandre-Moreno S, Bonet-Fernández J M, Atienzar-Aroca R, et al. Null cyp1b 1 activity in zebrafish leads to variable craniofacial defects associated with altered expression of extracellular matrix and lipid metabolism genes. International Journal of Molecular Sciences, 2021, 22(12): 6430.
doi: 10.3390/ijms22126430
[47] Cooper C, Peterson E J R, Bailo R, et al. MadR mediates acyl CoA-dependent regulation of mycolic acid desaturation in mycobacteria. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119(8): e2111059119.
[1] 张中素, 杨瑞刚, 朱凌云, 吴小敏. 提高微生物合成萜类化合物产量的策略[J]. 中国生物工程杂志, 2017, 37(1): 97-103.
[2] 耿梦婷, 姚远, 胡新文, 郭建春, 闵义. 木薯ftsZ基因分离及在原核生物中功能初步鉴定[J]. 中国生物工程杂志, 2013, 33(6): 24-29.
[3] 何彰华, 王洋, 赵珺, 刘晓杰, 张丽华, 王东, 师明磊, 黄芬, 尤平, 赵志虎. 一种多基因串联共表达载体的构建[J]. 中国生物工程杂志, 2011, 31(01): 40-45.
[4] 鞠传丽, 孔冬冬, 王东, 胡勇, 何奕昆. 原核生物细胞分裂的调控机制[J]. 中国生物工程杂志, 2002, 22(4): 17-21.
[5] 李艳, 王正祥, 诸葛健. 酵母作为外源基因表达系统的研究进展[J]. 中国生物工程杂志, 2001, 21(2): 10-14.
[6] 王渭池, 欧阳藩. 单细胞数学模型的进展[J]. 中国生物工程杂志, 1995, 15(3): 25-29.
[7] 魏祥龙, 吴明. 法国微生物生物工程学的研究与开发现状[J]. 中国生物工程杂志, 1992, 12(1): 29-34.
[8] HarryKlee, RobertHorsch, StephenRogers, 张毅. 农杆菌介导的植物转化及其将来在植物生物学中的应用[J]. 中国生物工程杂志, 1988, 8(5): 33-44.
[9] 李锦芳. 第一条人工染色体建成[J]. 中国生物工程杂志, 1984, 4(1): 83-84.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会