|
|
|
| Transcription Factor Engineering Harnesses Metabolic Networks to Meet Efficient Production in Cell Factories |
DONG Shu-xin1,QIN Lei2,LI Chun1,2,LI Jun1,*( ) |
1 School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
2 Department of Chemical Engineering,Tsinghua University, Beijing 100084, China |
|
|
|
Abstract Yeast has been well used as a typical microbial platform to make fermented fine chemicals. However, various stress conditions and abnormal metabolic milieu severely restrict the production costs and benefits. One effective way to resolve such bottlenecks is to engineer transcription factors (TFs) to enhance strain tolerance and production efficiency through remodeling the transcript levels of different stress resistant genes. The value of TFs engineering is reviewed from two aspects: novel strategies for the enhancement of both tolerance and yield by TFs engineering are examined. In addition, the applications of artificial transcription factors (ATFs)-based fabricating in metabolic fluxes optimization and quantitative evaluation are discussed. Lastly, we discuss challenges and potential solutions in exploiting TFs engineering for bio-based economic products.
|
|
Received: 23 December 2020
Published: 30 April 2021
|
|
|
|
Corresponding Authors:
Jun LI
E-mail: junlibiotech@bit.edu.cn
|
|
|
| [1] |
Caspeta L, Castillo T, Nielsen J. Modifying yeast tolerance to inhibitory conditions of ethanol production processes. Frontiers in Bioengineering and Biotechnology, 2015,3:184.
doi: 10.3389/fbioe.2015.00184
pmid: 26618154
|
|
|
| [2] |
Kuroda K, Hammer S K, Watanabe Y, et al. Critical roles of the pentose phosphate pathway and GLN3 in isobutanol-specific tolerance in yeast. Cell Systems, 2019,9(6):534-547,e5.
pmid: 31734159
|
|
|
| [3] |
Zhu Z W, Hu Y T, Teixeira P G, et al. Multidimensional engineering of Saccharomyces cerevisiae for efficient synthesis of medium-chain fatty acids. Nature Catalysis, 2020,3:64-74.
|
|
|
| [4] |
Pereira R, Wei Y J, Mohamed E, et al. Adaptive laboratory evolution of tolerance to dicarboxylic acids in Saccharomyces cerevisiae. Metabolic Engineering, 2019,56:130-141.
|
|
|
| [5] |
Otto M, Teixeira P G, Vizcaino M I, et al. Integration of a multi-step heterologous pathway in Saccharomyces cerevisiae for the production of abscisic acid. Microbial Cell Factories, 2019,18:205.
pmid: 31767000
|
|
|
| [6] |
梁欣泉, 李宁, 任勤, 等. 代谢工程改造酿酒酵母生产L-乳酸的研究进展. 中国生物工程杂志, 2016,36(2):109-114.
|
|
|
| [6] |
Liang X Q, Li N, Ren Q, et al. Progress in the metabolic engineering of Saccharomyces cerevisiae for L-lactic acid production. China Biotechnology, 2016,36(2):109-114.
|
|
|
| [7] |
Snoek T, Verstrepen K J, Voordeckers K. How do yeast cells become tolerant to high ethanol concentrations? Current Genetics, 2016,62:475-480.
doi: 10.1007/s00294-015-0561-3
pmid: 26758993
|
|
|
| [8] |
Auesukaree C. Molecular mechanisms of the yeast adaptive response and tolerance to stresses encountered during ethanol fermentation. Journal of Bioscience and Bioengineering, 2017,124(2):133-142.
doi: 10.1016/j.jbiosc.2017.03.009
pmid: 28427825
|
|
|
| [9] |
Gibson B R, Lawrence S J, Leclaire J P R, et al. Yeast responses to stresses associated with industrial brewery handling. FEMS Microbiology Reviews, 2007,31(5):535-569.
pmid: 17645521
|
|
|
| [10] |
Kovács D, Sigmond T, Hotzi B, et al. HSF1Base: a comprehensive database of HSF1 (heat shock factor 1) target genes. International Journal of Molecular Sciences, 2019,20(22):5815.
|
|
|
| [11] |
Kuang Z, Ji H K, Boeke J D. Stress response factors drive regrowth of quiescent cells. Current Genetics, 2018,64:807-810.
doi: 10.1007/s00294-018-0813-0
pmid: 29455333
|
|
|
| [12] |
Jethmalani S M, Henle K J. Interaction of heat stress glycoprotein GP50 with classical heat-shock proteins. Experimental Cell Research, 1998,239(1):23-30.
|
|
|
| [13] |
Li S, Giardina D M, Siegal M L. Control of nongenetic heterogeneity in growth rate and stress tolerance of Saccharomyces cerevisiae by cyclic AMP-regulated transcription factors. PLoS Genetics, 2018,14(11):e1007744.
doi: 10.1371/journal.pgen.1007744
pmid: 30388117
|
|
|
| [14] |
Torelli N Q, Ferreira-Júnior J R, Kowaltowski A J, et al. RTG1- and RTG2-dependent retrograde signaling controls mitochondrial activity and stress resistance in Saccharomyces cerevisiae. Free Radical Biology and Medicine, 2015,81:30-37.
doi: 10.1016/j.freeradbiomed.2014.12.025
pmid: 25578655
|
|
|
| [15] |
Komeili A, Wedaman K P, O’Shea E K, et al. Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors. The Journal of Cell Biology, 2000,151(4):863-878.
pmid: 11076970
|
|
|
| [16] |
Liu Z C, Sekito T, Špirek M, et al. Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mks1p. Molecular Cell, 2003,12(2):401-411.
doi: 10.1016/s1097-2765(03)00285-5
pmid: 14536080
|
|
|
| [17] |
Liu Z C, Spírek M, Thornton J, et al. A novel degron-mediated degradation of the RTG pathway regulator, Mks1p, by SCFGrr1. Molecular Biology of the Cell, 2005,16(10):4893-4904.
doi: 10.1091/mbc.e05-06-0516
pmid: 16093347
|
|
|
| [18] |
Liu Z C, Butow R A. Mitochondrial retrograde signaling. Annual Review of Genetics, 2006,40:159-185.
doi: 10.1146/annurev.genet.40.110405.090613
pmid: 16771627
|
|
|
| [19] |
Ruiz-Roig C, Noriega N, Duch A, et al. The Hog1 SAPK controls the Rtg1/Rtg3 transcriptional complex activity by multiple regulatory mechanisms. Molecular Biology of the Cell, 2012,23(21):4286-4296.
pmid: 22956768
|
|
|
| [20] |
Laera L, Guaragnella N, Ždralević M, et al. The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose. Microbial Cell (Graz, Austria), 2016,3(12):621-631.
|
|
|
| [21] |
Srinivasan V, Kriete A, Sacan A, et al. Comparing the yeast retrograde response and NF-κB stress responses: implications for aging. Aging Cell, 2010,9(6):933-941.
pmid: 20961379
|
|
|
| [22] |
Qu Z Z, Zhang L L, Zhu S M, et al. Overexpression of the transcription factor HAC1 improves nerolidol production in engineered yeast. Enzyme and Microbial Technology, 2020,134:109485.
pmid: 32044032
|
|
|
| [23] |
Tran D M, Ishiwata-Kimata Y, Mai T C, et al. The unfolded protein response alongside the diauxic shift of yeast cells and its involvement in mitochondria enlargement. Scientific Reports, 2019,9:12780.
doi: 10.1038/s41598-019-49146-5
pmid: 31484935
|
|
|
| [24] |
Alper H, Moxley J, Nevoigt E, et al. Engineering yeast transcription machinery for improved ethanol tolerance and production. Science, 2006,314(5805):1565-1568.
doi: 10.1126/science.1131969
pmid: 17158319
|
|
|
| [25] |
Chen Z, Zheng Z, Yi C F, et al. Intracellular metabolic changes in Saccharomyces cerevisiae and promotion of ethanol tolerance during the bioethanol fermentation process. RSC Advances, 2016,6(107):105046-105055.
|
|
|
| [26] |
Gao L M, Liu Y Q, Sun H, et al. Advances in mechanisms and modifications for rendering yeast thermotolerance. Journal of Bioscience and Bioengineering, 2016,121(6):599-606.
doi: 10.1016/j.jbiosc.2015.11.002
pmid: 26685013
|
|
|
| [27] |
Mat Nanyan N S B, Takagi H. Proline homeostasis in Saccharomyces cerevisiae: how does the stress-responsive transcription factor Msn2 play a role? Frontiers in Genetics, 2020,11:438.
pmid: 32411186
|
|
|
| [28] |
Li L T, Kaplan J, Ward D M. The glucose sensor Snf1 and the transcription factors Msn2 and Msn4 regulate transcription of the vacuolar iron importer gene CCC1 and iron resistance in yeast. Journal of Biological Chemistry, 2017,292(37):15577-15586.
|
|
|
| [29] |
Palma M, Guerreiro J F, Sá-Correia I. Adaptive response and tolerance to acetic acid in Saccharomyces cerevisiae and Zygosaccharomyces bailii: a physiological genomics perspective. Frontiers in Microbiology, 2018,9:274.
doi: 10.3389/fmicb.2018.00274
pmid: 29515554
|
|
|
| [30] |
Sakihama Y, Hasunuma T, Kondo A. Improved ethanol production from xylose in the presence of acetic acid by the overexpression of the HAA1 gene in Saccharomyces cerevisiae. Journal of Bioscience and Bioengineering, 2015,119(3):297-302.
pmid: 25282639
|
|
|
| [31] |
Cunha J T, Costa C E, Ferraz L, et al. HAA1 and PRS3 overexpression boosts yeast tolerance towards acetic acid improving xylose or glucose consumption: unravelling the underlying mechanisms. Applied Microbiology and Biotechnology, 2018,102(10):4589-4600.
doi: 10.1007/s00253-018-8955-z
pmid: 29607452
|
|
|
| [32] |
Chen Y Y, Stabryla L, Wei N. Improved acetic acid resistance in Saccharomyces cerevisiae by overexpression of the WHI2 gene identified through inverse metabolic engineering. Applied and Environmental Microbiology, 2016,82(7):2156-2166.
doi: 10.1128/AEM.03718-15
pmid: 26826231
|
|
|
| [33] |
Kim J E, Jang I S, Son S H, et al. Tailoring the Saccharomyces cerevisiae endoplasmic reticulum for functional assembly of terpene synthesis pathway. Metabolic Engineering, 2019,56:50-59.
pmid: 31445083
|
|
|
| [34] |
Qin L, Dong S X, Yu J, et al. Stress-driven dynamic regulation of multiple tolerance genes improves robustness and productive capacity of Saccharomyces cerevisiae in industrial lignocellulose fermentation. Metabolic Engineering, 2020,61:160-170.
pmid: 32553944
|
|
|
| [35] |
Wei S, Liu Y N, Wu M L, et al. Disruption of the transcription factors Thi2p and Nrm1p alleviates the post-glucose effect on xylose utilization in Saccharomyces cerevisiae. Biotechnology for Biofuels, 2018,11:112.
pmid: 29686730
|
|
|
| [36] |
Wei S, Bai P G, Liu Y N, et al. A Thi2p regulatory network controls the post-glucose effect of xylose utilization in Saccharomyces cerevisiae. Frontiers in Microbiology, 2019,10:1649.
pmid: 31379793
|
|
|
| [37] |
Fang T S, Yan H B, Li G Z, et al. Chromatin remodeling complexes are involvesd in the regulation of ethanol production during static fermentation in budding yeast. Genomics, 2020,112(2):1674-1679.
doi: 10.1016/j.ygeno.2019.10.005
pmid: 31618673
|
|
|
| [38] |
Peterson C L, Zhao Y, Chait B T. Subunits of the yeast SWI/SNF complex are members of the actin-related protein (ARP) family. The Journal of Biological Chemistry, 1998,273(37):23641-23644.
doi: 10.1074/jbc.273.37.23641
pmid: 9726966
|
|
|
| [39] |
Peterson C L, Herskowitz I. Characterization of the yeast SWI1, SWI2, and SWI3 genes, which encode a global activator of transcription. Cell, 1992,68(3):573-583.
pmid: 1339306
|
|
|
| [40] |
Antonets K S, Kliver S F, Polev D E, et al. Distinct mechanisms of phenotypic effects of inactivation and prionization of Swi1 protein in Saccharomyces cerevisiae. Biochemistry (Moscow), 2017,82(10):1147-1157.
|
|
|
| [41] |
Zhang Y F, Anderson S J, French S L, et al. The SWI/SNF chromatin remodeling complex influences transcription by RNA polymerase I in Saccharomyces cerevisiae. PLoS One, 2013,8(2):e56793.
doi: 10.1371/journal.pone.0056793
pmid: 23437238
|
|
|
| [42] |
Dastidar R G, Hooda J, Shah A, et al. The nuclear localization of SWI/SNF proteins is subjected to oxygen regulation. Cell & Bioscience, 2012,2:30.
pmid: 22932476
|
|
|
| [43] |
Li P S, Fu X F, Zhang L, et al. The transcription factors Hsf1 and Msn2 of thermotolerant Kluyveromyces marxianus promote cell growth and ethanol fermentation of Saccharomyces cerevisiae at high temperatures. Biotechnology for Biofuels, 2017,10:289.
pmid: 29213328
|
|
|
| [44] |
Veri A O, Robbins N, Cowen L E. Regulation of the heat shock transcription factor Hsf1 in fungi: implications for temperature-dependent virulence traits. FEMS Yeast Research, 2018,18(5):foy041.
|
|
|
| [45] |
Kuki Y, Ohno R, Yoshida K, et al. Heterologous expression of wheat WRKY transcription factor genes transcriptionally activated in hybrid necrosis strains alters abiotic and biotic stress tolerance in transgenic Arabidopsis. Plant Physiology and Biochemistry, 2020,150:71-79.
doi: 10.1016/j.plaphy.2020.02.029
pmid: 32120271
|
|
|
| [46] |
Nghia D H T, Chuong N N, Hoang X L T, et al. Heterologous expression of a soybean gene RR34 conferred improved drought resistance of transgenic Arabidopsis. Plants, 2020,9(4):494.
|
|
|
| [47] |
Wang L, Liu W D, Wang Y J. Heterologous expression of Chinese wild grapevine VqERFs in Arabidopsis thaliana enhance resistance to Pseudomonas syringae pv. tomato DC3000 and to Botrytis cinerea. Plant Science, 2020,293:110421.
pmid: 32081269
|
|
|
| [48] |
Yao L N, Hao X Y, Cao H L, et al. ABA-dependent bZIP transcription factor, CsbZIP18, from Camellia sinensis negatively regulates freezing tolerance in Arabidopsis. Plant Cell Reports, 2020,39:553-565.
pmid: 32060604
|
|
|
| [49] |
Du X Y, He F, Zhu B, et al. NAC transcription factors from Aegilops markgrafii reduce cadmium concentration in transgenic wheat. Plant and Soil, 2020,449:39-50.
|
|
|
| [50] |
Wan F X, Pan Y, Li J H, et al. Heterologous expression of Arabidopsis C-repeat binding factor 3 (AtCBF3) and cold-regulated 15A (AtCOR15A) enhanced chilling tolerance in transgenic eggplant (Solanum melongena L.). Plant Cell Reports, 2014,33:1951-1961.
pmid: 25103420
|
|
|
| [51] |
Zhao P C, Hou S L, Guo X F, et al. A MYB-related transcription factor from sheepgrass, LcMYB2, promotes seed germination and root growth under drought stress. BMC Plant Biology, 2019,19(1):564.
doi: 10.1186/s12870-019-2159-2
pmid: 31852429
|
|
|
| [52] |
贺雪婷, 张敏华, 洪解放, 等. 大肠杆菌丁醇耐受机制及耐受菌选育研究进展. 中国生物工程杂志, 2018,38(9):81-87.
|
|
|
| [52] |
He X T, Zhang M H, Hong J F, et al. Research progress on butanol-tolerant strain and tolerance mechanism of Escherichia coli. China Biotechnology, 2018,38(9):81-87.
|
|
|
| [53] |
Michael D G, Maier E J, Brown H, et al. Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast. PNAS, 2016,113(47):E7428-E7437.
pmid: 27810962
|
|
|
| [54] |
Liu H M, Yan M, Lai C G, et al. gTME for improved xylose fermentation of Saccharomyces cerevisiae. Applied Biochemistry and Biotechnology, 2010,160:574-582.
pmid: 19067246
|
|
|
| [55] |
Srivastava R, Rai K M, Pandey B, et al. Spt-Ada-Gcn5-acetyltransferase (SAGA) complex in plants: genome wide identification, evolutionary conservation and functional determination. PLoS One, 2015,10(8):e0134709.
doi: 10.1371/journal.pone.0134709
pmid: 26263547
|
|
|
| [56] |
Canzonetta C, Leo M, Guarino S R, et al. SAGA complex and Gcn5 are necessary for respiration in budding yeast. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2016,1863(12):3160-3168.
|
|
|
| [57] |
Warfield L, Ramachandran S, Baptista T, et al. Transcription of nearly all yeast RNA polymerase II-transcribed genes is dependent on transcription factor TFIID. Molecular Cell, 2017,68(1):118-129,e5.
pmid: 28918900
|
|
|
| [58] |
Ansari S A, Ganapathi M, Benschop J J, et al. Distinct role of Mediator tail module in regulation of SAGA-dependent, TATA-containing genes in yeast. The EMBO Journal, 2012,31(1):44-57.
pmid: 21971086
|
|
|
| [59] |
Xue T, Chen D, Su Q Q, et al. Improved ethanol tolerance and production of Saccharomyces cerevisiae by global transcription machinery engineering via directed evolution of the SPT8 gene. Food Biotechnology, 2019,33(2):155-173.
|
|
|
| [60] |
Zhu L Y, Gao S, Zhang H M, et al. Improvement of lead tolerance of Saccharomyces cerevisiae by random mutagenesis of transcription regulator SPT3. Applied Biochemistry and Biotechnology, 2018,184(1):155-167.
pmid: 28656551
|
|
|
| [61] |
Phithakrotchanakoon C, Puseenam A, Wongwisansri S, et al. CRISPR-Cas9 enabled targeted mutagenesis in the thermotolerant methylotrophic yeast Ogataea thermomethanolica. FEMS Microbiology Letters, 2018,365(11):fny105.
|
|
|
| [62] |
Urnov F D, Rebar E J. Designed transcription factors as tools for therapeutics and functional genomics. Biochemical Pharmacology, 2002,64(5-6):919-923.
doi: 10.1016/s0006-2952(02)01150-4
pmid: 12213587
|
|
|
| [63] |
Heiderscheit E A, Eguchi A, Spurgat M C, et al. Reprogramming cell fate with artificial transcription factors. FEBS Letters, 2018,592(6):888-900.
pmid: 29389011
|
|
|
| [64] |
Chattopadhyay A, Purohit J, Tiwari K K, et al. Targeting transcription factors for plant disease resistance: shifting paradigm. Current Science, 2019,117(10):1598-1607.
|
|
|
| [65] |
Liu W S, Stewart C N J. Plant synthetic promoters and transcription factors. Current Opinion in Biotechnology, 2016,37:36-44.
doi: 10.1016/j.copbio.2015.10.001
pmid: 26524248
|
|
|
| [66] |
Purcell O, Peccoud J, Lu T K. Rule-based design of synthetic transcription factors in eukaryotes. ACS Synthetic Biology, 2014,3(10):737-744.
|
|
|
| [67] |
Klug A. The discovery of zinc fingers and their development for practical applications in gene regulation and genome manipulation. Quarterly Reviews of Biophysics, 2010,43(1):1-21.
pmid: 20478078
|
|
|
| [68] |
Lee J Y, Sung B H, Yu B J, et al. Phenotypic engineering by reprogramming gene transcription using novel artificial transcription factors in Escherichia coli. Nucleic Acids Research, 2008,36(16):e102.
doi: 10.1093/nar/gkn449
pmid: 18641039
|
|
|
| [69] |
Lee J Y, Yang K S, Jang S A, et al. Engineering butanol-tolerance in Escherichia coli with artificial transcription factor libraries. Biotechnology and Bioengineering, 2011,108(4):742-749.
pmid: 21404248
|
|
|
| [70] |
Park K S, Lee D K, Lee H, et al. Phenotypic alteration of eukaryotic cells using randomized libraries of artificial transcription factors. Nature Biotechnology, 2003,21(10):1208-1214.
doi: 10.1038/nbt868
pmid: 12960965
|
|
|
| [71] |
Ma C, Wei X W, Sun C H, et al. Improvement of acetic acid tolerance of Saccharomyces cerevisiae using a zinc-finger-based artificial transcription factor and identification of novel genes involved in acetic acid tolerance. Applied Microbiology and Biotechnology, 2015,99(5):2441-2449.
doi: 10.1007/s00253-014-6343-x
pmid: 25698512
|
|
|
| [72] |
Rantasalo A, Kuivanen J, Penttilä M, et al. Synthetic toolkit for complex genetic circuit engineering in Saccharomyces cerevisiae. ACS Synthetic Biology, 2018,7(6):1573-1587.
pmid: 29750501
|
|
|
| [73] |
Naseri G, Balazadeh S, Machens F, et al. Plant-derived transcription factors for orthologous regulation of gene expression in the yeast Saccharomyces cerevisiae. ACS Synthetic Biology, 2017,6(9):1742-1756.
pmid: 28531348
|
|
|
| [74] |
Naseri G, Behrend J, Rieper L, et al. COMPASS for rapid combinatorial optimization of biochemical pathways based on artificial transcription factors. Nature Communications, 2019,10:2615.
pmid: 31197154
|
|
|
| [75] |
Machens F, Balazadeh S, Mueller-Roeber B, et al. Synthetic promoters and transcription factors for heterologous protein expression in Saccharomyces cerevisiae. Frontiers in Bioengineering and Biotechnology, 2017,5:63.
pmid: 29098147
|
|
|
| [76] |
Rantasalo A, Landowski C P, Kuivanen J, et al. A universal gene expression system for fungi. Nucleic Acids Research, 2018,46(18):e111.
pmid: 29924368
|
|
|
| [77] |
Nguyen N H, Kim J R, Park S. Development of biosensor for 3-hydroxypropionic acid. Biotechnology and Bioprocess Engineering, 2019,24:109-118.
|
|
|
| [78] |
Durai L, Vijayalakshmi R, Karunagaran D. A novel reporter system for cyclic AMP mediated gene expression in mammalian cells based on synthetic transgene expression system. European Journal of Pharmacology, 2019,855:56-64.
pmid: 31034821
|
|
|
| [79] |
Li J W, Zhang X Y, Wu H, et al. Transcription factor engineering for high-throughput strain evolution and organic acid bioproduction: a review. Frontiers in Bioengineering and Biotechnology, 2020,8:98.
pmid: 32140463
|
|
|
| [80] |
Myers K S, Riley N M, MacGilvray M E, et al. Rewired cellular signaling coordinates sugar and hypoxic responses for anaerobic xylose fermentation in yeast. PLoS Genetics, 2019,15(3):e1008037.
pmid: 30856163
|
|
|
| [81] |
Yang T H. Transcription factor regulatory modules provide the molecular mechanisms for functional redundancy observed among transcription factors in yeast. BMC Bioinformatics, 2019,20(Suppl 23):630.
pmid: 31881824
|
|
|
| [82] |
Thorwall S, Schwartz C, Chartron J W, et al. Stress-tolerant non-conventional microbes enable next-generation chemical biosynthesis. Nature Chemical Biology, 2020,16:113-121.
pmid: 31974527
|
|
|
| [83] |
Xu K, Qin L, Bai W X, et al. Multilevel defense system (MDS) relieves multiple stresses for economically boosting ethanol production of industrial Saccharomyces cerevisiae. ACS Energy Letters, 2020,5(2):572-582.
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
