Abstract
Promoter engineering is an enabling technology in metabolic engineering and synthetic biology. As an indispensable part of synthetic biology, the promoter is a key factor in regulating genetic circuits and in coordinating multi-gene biosynthetic pathways. In this review, we summarized the recent progresses in promoter engineering in microbes. Specifically, the endogenous promoters are firstly discussed, followed by the statement of the influence of nucleotides exchange on the strength of promoters explored by site-selective mutagenesis. We then introduced the promoter libraries with a wide range of strength, which are constructed focusing on core promoter regions and upstream activating sequences by rational designs. Finally, the application of promoter libraries in the optimization of multi-gene metabolic pathways for high-yield production of metabolites was illustrated with a couple of recent examples.
Similar content being viewed by others
References
Adams BG (1972) Induction of galactokinase in Saccharomyces cerevisiae: kinetics of induction and glucose effects. J Bacteriol 111(2):308–315
Alper H, Fischer C, Nevoigt E, Stephanopoulos G (2005) Tuning genetic control through promoter engineering. Proc Natl Acad Sci U S A 102(36):12678–12683. https://doi.org/10.1073/pnas.0504604102
Babiskin AH, Smolke CD (2011) A synthetic library of RNA control modules for predictable tuning of gene expression in yeast. Mol Syst Biol 7:471. https://doi.org/10.1038/msb.2011.4
Basehoar AD, Zanton SJ, Pugh BF (2004) Identification and distinct regulation of yeast TATA box-containing genes. Cell 116(5):699–709. https://doi.org/10.1016/S0092-8674(04)00205-3
Bitter GA, Egan KM (1984) Expression of heterologous genes in Saccharomyces cerevisiae from vectors utilizing the glyceraldehyde-3-phosphate dehydrogenase gene promoter. Gene 32(3):263–274. https://doi.org/10.1155/2013/268249
Blazeck J, Alper HS (2013) Promoter engineering: recent advances in controlling transcription at the most fundamental level. Biotechnol J 8(1):46. https://doi.org/10.1002/biot.201200120
Blazeck J, Liu LQ, Redden H, Alper H (2011) Tuning gene expression in Yarrowia lipolytica by a hybrid promoter approach. Appl Environ Microbiol 77(22):7905–7914. https://doi.org/10.1128/aem.05763-11
Blazeck J, Garg R, Reed B, Alper HS (2012) Controlling promoter strength and regulation in Saccharomyces cerevisiae using synthetic hybrid promoters. Biotechnol Bioeng 109(11):2884–2895. https://doi.org/10.1002/bit.24552
Blazeck J, Reed B, Garg R, Gerstner R, Pan A, Agarwala V, Alper HS (2013) Generalizing a hybrid synthetic promoter approach in Yarrowia lipolytica. Appl Microbiol Biotechnol 97(7):3037–3052. https://doi.org/10.1007/s00253-012-4421-5
Blazeck J, Miller J, Pan A, Gengler J, Holden C, Jamoussi M, Alper HS (2014) Metabolic engineering of Saccharomyces cerevisiae for itaconic acid production. Appl Microbiol Biotechnol 98(19):8155–8164. https://doi.org/10.1007/s00253-014-5895-0
Blount BA, Weenink T, Vasylechko S, Ellis T (2012) Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology. PLoS One 7(3):e33279. https://doi.org/10.1371/journal.pone.0033279
Boer HA, Comstock LJ, Vasser M (1983) The tac promoter: a functional hybrid derived from the trp and lac promoters. Proc Natl Acad Sci U S A 80(1):21–25. https://doi.org/10.1073/pnas.80.1.21
Brewster RC, Jones DL, Phillips R (2012) Tuning promoter strength through RNA polymerase binding site design in Escherichia coli. PLoS Comput Biol 8(12):e1002811. https://doi.org/10.1371/journal.pcbi.1002811
Bulter T, Lee SG, Wong WW, Fung E, Connor MR, Liao JC (2004) Design of artificial cell-cell communication using gene and metabolic networks. Proc Natl Acad Sci U S A 101(8):2299–2304. https://doi.org/10.1073/pnas.0306484101
Clomburg JM, Gonzalez R (2010) Biofuel production in Escherichia coli: the role of metabolic engineering and synthetic biology. Appl Microbiol Biotechnol 86(2):419–434. https://doi.org/10.1007/s00253-010-2446-1
Denis CL, Ferguson J, Young ET (1983) mRNA levels for the fermentative alcohol dehydrogenase of Saccharomyces cerevisiae decrease upon growth on a nonfermentable carbon source. J Biol Chem 258(2):1165–1171
Diderich JA, Schepper M, van Hoek P, Luttik MA, van Dijken JP, Pronk JT, Klaassen P, Boelens HF, de Mattos MJ, van Dam K, Kruckeberg AL (1999) Glucose uptake kinetics and transcription of HXT genes in chemostat cultures of Saccharomyces cerevisiae. J Biol Chem 274(22):15350–15359. https://doi.org/10.1074/jbc.274.22.15350
Donohoue PD, Barrangou R, May AP (2018) Advances in industrial biotechnology using CRISPR-Cas systems. Trends Biotechnol 36(2):135–146. https://doi.org/10.1016/j.tibtech.2017.07.007
Dunlop MJ, Keasling JD, Mukhopadhyay A (2010) A model for improving microbial biofuel production using a synthetic feedback loop. Syst Synth Biol 4(2):95–104. https://doi.org/10.1007/s11693-010-9052-5
Gatignol A, Dassain M, Tiraby G (1990) Cloning of Saccharomyces cerevisiae promoters using a probe vector based on phleomycin resistance. Gene 91(1):35–41. https://doi.org/10.1016/0378-1119(90)90159-O
Gertz J, Siggia ED, Cohen BA (2009) Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature 457(7226):215–218. https://doi.org/10.1038/nature07521
Gorochowski TE, van den Berg E, Kerkman R, Roubos JA, Bovenberg RA (2014) Using synthetic biological parts and microbioreactors to explore the protein expression characteristics of Escherichia coli. ACS Synth Biol 3(3):129–139. https://doi.org/10.1021/sb4001245
Guan CR, Cui WJ, Cheng JT, Zhou L, Guo JL, Hu X, Xiao GP, Zhou ZM (2015) Construction and development of an auto-regulatory gene expression system in Bacillus subtilis. Microb Cell Factories 14(1):150. https://doi.org/10.1186/s12934-015-0341-2
Hartner FS, Ruth C, Langenegger D, Johnson SN, Hyka P, Lincereghino GP, Lincereghino J, Kovar K, Cregg JM, Glieder A (2008) Promoter library designed for fine-tuned gene expression in Pichia pastoris. Nucleic Acids Res 36(12):e76. https://doi.org/10.1093/nar/gkn369
Horbal L, Fedorenko V, Luzhetskyy A (2014) Novel and tightly regulated resorcinol and cumate-inducible expression systems for Streptomyces and other actinobacteria. Appl Microbiol Biotechnol 98(20):8641–8655. https://doi.org/10.1007/s00253-014-5918-x
Huang JF, Liu ZQ, Jin LQ, Tang XL, Shen ZY, Yin HH, Zheng YG (2016) Metabolic engineering of Escherichia coli for microbial production of L-methionine. Biotechnol Bioeng 114(4):843–851. https://doi.org/10.1002/bit.26198
Huang JF, Shen ZY, Mao QL, Zhang XM, Zhang B, Wu JS, Liu ZQ, Zheng YG (2018) Systematic analysis of bottlenecks in a multibranched and multilevel regulated pathway: the molecular fundamentals of l -methionine biosynthesis in Escherichia coli. ACS Synth Biol 7(11):2577–2589. https://doi.org/10.1021/acssynbio.8b00249
Jha RK, Kern TL, Fox DT, M Strauss CE (2014) Engineering an acinetobacter regulon for biosensing and high-throughput enzyme screening in E. coli via flow cytometry. Nucleic Acids Res 42(12):8150–8160. https://doi.org/10.1093/nar/gku444
Jiao S, Li X, Yu HM, Yang H, Li X, Shen ZY (2017) In situ enhancement of surfactin biosynthesis in Bacillus subtilis using novel artificial inducible promoters. Biotechnol Bioeng 114(4):832–842. https://doi.org/10.1002/bit.26197
John TPS, Davis RW (1981) The organization and transcription of the galactose gene cluster of Saccharomyces. J Mol Biol 152(2):285–315. https://doi.org/10.1016/0022-2836(81)90244-8
Jung YK, Kim TY, Park SJ, Lee SY (2010) Metabolic engineering of Escherichia coli for the production of polylactic acid and its copolymers. Biotechnol Bioeng 105(1):161–171. https://doi.org/10.1002/bit.22548
Juven GT, Kadonaga JT (2010) Regulation of gene expression via the core promoter and the basal transcriptional machinery. Dev Biol 339(2):225–229. https://doi.org/10.1016/j.ydbio.2009.08.009
Kagiya G, Ogawa R, Hatashita M, Takagi K, Kodaki T, Hiroishi S, Yamamoto K (2005) Generation of a strong promoter for Escherichia coli from eukaryotic genome DNA. J Biotechnol 115(3):239–248. https://doi.org/10.1016/j.jbiotec.2004.08.015
Kim S, Lee K, Bae S-J, Hahn J-S (2015) Promoters inducible by aromatic amino acids and γ-aminobutyrate (GABA) for metabolic engineering applications in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 99(6):2705–2714. https://doi.org/10.1007/s00253-014-6303-5
Kinney J, Murugan A, Callan CG, Cox EC (2010) Using deep sequencing to characterize the biophysical mechanism of a transcriptional regulatory sequence. Proc Natl Acad Sci U S A 107(20):9158–9163. https://doi.org/10.1073/pnas.1004290107
Kodym A, Afza R (2003) Physical and chemical mutagenesis. Methods Mol Biol 236:189–204. https://doi.org/10.1385/1-59259-413-1:189
König L, Hartz P, Bernhardt R, Hannemann F (2019) High-yield C11-oxidation of hydrocortisone by establishment of an efficient whole-cell system in Bacillus megaterium. Metab Eng 55:59–67. https://doi.org/10.1016/j.ymben.2019.06.005
Kosuri S, Goodman DB, Cambray G, Mutalik VK, Gao Y, Arkin AP, Endy D, Church GM (2013) Composability of regulatory sequences controlling transcription and translation in Escherichia coli. Proc Natl Acad Sci U S A 110(34):14024–14029. https://doi.org/10.1073/pnas.1301301110
Lara AR, Jaen KE, Sigala JC, Muhlmann M, Regestein L, Buchs J (2017) Characterization of endogenous and reduced promoters for oxygen-limited processes using Escherichia coli. ACS Synth Biol 6(2):344–356. https://doi.org/10.1021/acssynbio.6b00233
Latimer LN, Lee ME, Medina-Cleghorn D, Kohnz RA, Nomura DK, Dueber JE (2014) Employing a combinatorial expression approach to characterize xylose utilization in Saccharomyces cerevisiae. Metab Eng 25:20–29. https://doi.org/10.1016/j.ymben.2014.06.002
Laughon A, Gesteland RF (1982) Isolation and preliminary characterization of the GAL4 gene, a positive regulator of transcription in yeast. Proc Natl Acad Sci U S A 79(22):6827–6831. https://doi.org/10.1073/pnas.79.22.6827
Li TT, Li T, Ji WY, Wang QY, Zhang HQ, Chen GQ, Lou CB, Ouyang Q (2016) Engineering of core promoter regions enables the construction of constitutive and inducible promoters in Halomonas sp. Biotechnol J 11(2):219–227. https://doi.org/10.1002/biot.201400828
Ling MX, Liu YF, Li JH, Shin H–d, Chen J, Du GC LL (2017) Combinatorial promoter engineering of glucokinase and phosphoglucoisomerase for improved N-acetylglucosamine production in Bacillus subtilis. Bioresource Technol 245:1093–1102. https://doi.org/10.1016/j.biortech.2017.09.063
Liu Q, Wu KY, Cheng YB, Lu L, Xiao ET, Zhang YC, Deng ZX, Liu TG (2015) Engineering aniterative polyketide pathway in Escherichia coli results in single-form alkene and alkane overproduction. Metab Eng 28:82–90. https://doi.org/10.1016/j.ymben.2014.12.004
Liu D, Liu H, Li BZ, Qi H, Jia B, Zhou X, Du HX, Zhang W, Yuan YJ (2016) Multigene pathway engineering with regulatory linkers (M-PERL). ACS Synth Biol 5(12):1535–1545. https://doi.org/10.1021/acssynbio.6b00123
Lubliner S, Keren L, Segal E (2013) Sequence features of yeast and human core promoters that are predictive of maximal promoter activity. Nucleic Acids Res 41(11):5569–5581. https://doi.org/10.1093/nar/gkt256
Lubliner S, Regev I, Lotanpompan M, Edelheit S, Weinberger A, Segal E (2015) Core promoter sequence in yeast is a major determinant of expression level. Genome Res 25(7):1008–1017. https://doi.org/10.1101/gr.188193.114
Madzak C, Tréton B, Blanchin-Roland S (2000) Strong hybrid promoters and integrative expression/secretion vectors for quasi-constitutive expression of heterologous proteins in the yeast Yarrowia lipolytica. J Mol Microbiol Biotechnol 2(2):207–216
Mannan AA, Liu D, Zhang FZ, Oyarzún DA (2017) Fundamental design principles for transcription-factor-based metabolite biosensors. ACS Synth Biol 6(10):1851–1859. https://doi.org/10.1021/acssynbio.7b00172
Marjan DM, Jo M, Gaspard JL, Wim KS, Erick JV (2007) Construction and model-based analysis of a promoter library for E. coli: an indispensable tool for metabolic engineering. BMC Biotechnol 7(1):34. https://doi.org/10.1186/1472-6750-7-34
Matsushika A, Inoue H, Kodaki T, Sawayama S (2009) Ethanol production from xylose in engineered Saccharomyces cerevisiae strains: current state and perspectives. Appl Microbiol Biotechnol 84(1):37–53. https://doi.org/10.1007/s00253-009-2101-x
Moser F, Espah Borujeni A, Ghodasara AN, Cameron E, Park Y, Voigt CA (2018) Dynamic control of endogenous metabolism with combinatorial logic circuits. Mol Syst Biol 14(11):e8605. https://doi.org/10.15252/msb.20188605
Nevoigt E, Kohnke J, Fischer CR, Alper H, Stahl U, Stephanopoulos G (2006) Engineering of promoter replacement cassettes for fine-tuning of gene expression in Saccharomyces cerevisiae. Appl Environ Microbiol 72(8):5266–5273. https://doi.org/10.1128/aem.00530-06
Nishizawa M, Araki R, Teranishi Y (1989) Identification of an upstream activating sequence and an upstream repressible sequence of the pyruvate kinase gene of the yeast Saccharomyces cerevisiae. Mol Cell Biol 9(2):442–451. https://doi.org/10.1128/MCB.9.2.442
Ogden JE, Stanway C, Kim S, Mellor J, Kingsman AJ, Kingsman SM (1986) Efficient expression of the Saccharomyces cerevisiae PGK gene depends on an upstream activation sequence but does not require TATA sequences. Mol Cell Biol 6(12):4335–4343. https://doi.org/10.1128/MCB.6.12.4335
Österberg S, Pesosantos TD, Shingler V (2011) Regulation of alternative sigma factor use. Annu Rev Microbiol 65(1):37–55. https://doi.org/10.1146/ANNUREV.MICRO.112408.134219
Oyarzún DA, Stan GBV (2013) Synthetic gene circuits for metabolic control: design trade-offs and constraints. J R Soc Interface 10(78). https://doi.org/10.1098/rsif.2012.0671
Park SH, Kim HU, Kim TY, Park JS, Kim S-S, Lee SY (2014) Metabolic engineering of Corynebacterium glutamicum for L-arginine production. Nat Commun 5:4618. https://doi.org/10.1038/ncomms5618
Patwardhan RP, Lee C, Litvin O, Young DL, Pe’Er D, Shendure J (2009) High-resolution analysis of DNA regulatory elements by synthetic saturation mutagenesis. Nat Biotechnol 27(12):1173–1175. https://doi.org/10.1038/nbt.1589
Portela RMC, Vogl T, Kniely C, Fischer JE, Oliveira R, Glieder A (2017) Synthetic core promoters as universal parts for fine-tuning expression in different yeast species. ACS Synth Biol 6(3):471–484. https://doi.org/10.1021/acssynbio.6b00178
Qin XL, Qian JC, Yao GF, Zhuang YP, Zhang SL, Chu J (2011) GAP promoter library for fine-tuning of gene expression in Pichia pastoris. Appl Environ Microbiol 77(11):3600–3608. https://doi.org/10.1128/AEM.02843-10
Ramos JL, Manuel MB, Molina-Henares AJ, Wilson T, Kazuya W, Xiaodong Z, María Trinidad G, Richard B, Raquel T (2005) The TetR family of transcriptional repressors. Microbiol Mol Biol Rev 69(2):326–356. https://doi.org/10.1128/MMBR.69.2.326-356.2005
Redden H, Morse N, Alper HS (2014) The synthetic biology toolbox for tuning gene expression in yeast. FEMS Yeast Res 15(1):1. https://doi.org/10.1111/1567-1364.12188
Reifenberger E, Boles E, Ciriacy M (2010) Kinetic characterization of individual hexose transporters of Saccharomyces cerevisiae and their relation to the triggering mechanisms of glucose repression. Eur J Biochem 245(2):324–333. https://doi.org/10.1111/j.1432-1033.1997.00324.x
Rud I, Jensen PR, Naterstad K, Axelsson L (2006) A synthetic promoter library for constitutive gene expression in Lactobacillus plantarum. Microbiol 152:1011–1019. https://doi.org/10.1099/mic.0.28599-0
Rui P, Thomas V, Katharina E, Rui O, Anton G (2018) Pichia pastoris alcohol oxidase 1 (AOX1) core promoter engineering by high resolution systematic mutagenesis. Biotechnol J 13(3):1700340. https://doi.org/10.1002/biot.201700340
Ruth C, Zuellig T, Mellitzer A, Weis R, Looser V, Kovar K, Glieder A (2010) Variable production windows for porcine trypsinogen employing synthetic inducible promoter variants in Pichia pastoris. Syst Synth Biol 4(3):181–191. https://doi.org/10.1007/s11693-010-9057-0
Shabbir-Hussain M, Wheeldon I, Blenner MA (2017) A strong hybrid fatty acid inducible transcriptional sensor built from Yarrowia lipolytica upstream activating and regulatory sequences. Biotechnol J 12(10):1700268. https://doi.org/10.1002/biot.201700248
Shao ZY, Zhao H, Zhao HM (2009) DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Res 37(2):e16. https://doi.org/10.1093/nar/gkn991
Sharon E, Al E (2012) Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters. Nat Biotechnol 30(6):521–530. https://doi.org/10.1038/nbt.2205
Shibui T, Uchida M, Teranishi Y (1988) A new hybrid promoter and its expression vector in Escherichia coli. Agric Biol Chem 52(4):983–988. https://doi.org/10.1080/00021369.1988.10868770
Shukal S, Chen XX, Zhang CQ (2019) Systematic engineering for high-yield production of viridiflorol and amorphadiene in auxotrophic Escherichia coli. Metab Eng 55:170–178. https://doi.org/10.1016/j.ymben.2019.07.007
Siegl T, Tokovenko B, Myronovskyi M, Luzhetskyy A (2013) Design, construction and characterisation of a synthetic promoter library for fine-tuned gene expression in actinomycetes. Metab Eng 19(5):98–106. https://doi.org/10.1016/j.ymben.2013.07.006
Singh V (2014) Recent advances and opportunities in synthetic logic gates engineering in living cells. Syst Synth Biol 8(4):271–282. https://doi.org/10.1007/s11693-014-9154-6
Sun J, Shao ZY, Zhao H, Nair N, Wen F, Xu JH, Zhao HM (2012) Cloning and characterization of a panel of constitutive promoters for applications in pathway engineering in Saccharomyces cerevisiae. Biotechnol Bioeng 109(8):2082–2092. https://doi.org/10.1002/bit.24481
Teo WS, Chang MW (2013) Development and characterization of AND-gate dynamic controllers with a modular synthetic GAL1 core promoter in Saccharomyces cerevisiae. Biotechnol Bioeng 111(1):144–151. https://doi.org/10.1002/bit.25001
Vidal-Ingigliardi D, Raibaud O (1985) The mac promoters: functional hybrid promoters activated by the malT product and repressed by the lacI product. Nucleic Acids Res 13(4):1163–1172. https://doi.org/10.1093/nar/13.4.1163
Vinces MD, Legendre M, Caldara M, Hagihara M, Verstrepen KJ (2009) Unstable tandem repeats in promoters confer transcriptional evolvability. Science (New York, NY) 324(5931):1213–1216. https://doi.org/10.1126/science.1170097
Vogl T, Ruth C, Pitzer J, Kickenweiz T, Glieder A (2014) Synthetic core promoters for Pichia pastoris. ACS Synth Biol 3(3):188–191. https://doi.org/10.1021/sb400091p
Xu P, Li LY, Zhang FM, Stephanopoulos G, Koffas M (2014a) Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. Proc Natl Acad Sci U S A 111(31):11299–11304. https://doi.org/10.1073/pnas.1406401111
Xu YQ, Chu HP, Gao C, Tao F, Zhou ZK, Li K, Li LX, Ma CQ, Xu P (2014b) Systematic metabolic engineering of Escherichia coli for high-yield production of fuel bio-chemical 2,3-butanediol. Metab Eng 23:22–33. https://doi.org/10.1016/j.ymben.2014.02.004
Yan Q, Fong SS (2017) Study of in vitro transcriptional binding effects and noise using constitutive promoters combined with UP element sequences in Escherichia coli. J Biol Eng 11(1):33–11. https://doi.org/10.1186/s13036-017-0075-2
Yasutaro F, Hiroshi M, Kazutake H (2010) Regulation of fatty acid metabolism in bacteria. Mol Microbiol 66(4):829–839. https://doi.org/10.1111/j.1365-2958.2007.05947.x
Yim H, Haselbeck R, Niu W, Pujol-Baxley C, Burgard A, Boldt J, Khandurina J, Trawick JD, Osterhout RE, Stephen R, Estadilla J, Teisan S, Schreyer HB, Andrae S, Yang TH, Lee SY, Burk MJ, Van Dien S (2011) Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. Nat Chem Biol 7(7):445–452. https://doi.org/10.1038/nchembio.580
Yu JH, Zhu LW, Li HM, Tang YL, Liang XH, Chen T, Tang YJ (2016) Combinatorial optimization of CO2 transport and fixation to improve succinate production by promoter engineering. Biotechnol Bioeng 113(7):1531–1541. https://doi.org/10.1002/bit.25927
Zhang FZ, Carothers JM, Keasling JD (2012) Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids. Nat Biotechnol 30(4):354–359. https://doi.org/10.1038/nbt.2149
Zhang X, Zhang XF, Li HP, Wang LY, Zhang C, Xing XH, Bao CY (2014) Atmospheric and room temperature plasma (ARTP) as a new powerful mutagenesis tool. Appl Microbiol Biotechnol 98(12):5387–5396. https://doi.org/10.1007/s00253-014-5755-y
Zhang CQ, Chen XX, Lindley ND, Too HP (2018a) A “plug-n-play” modular metabolic system for the production of apocarotenoids. Biotechnol Bioeng 115(1):174–183. https://doi.org/10.1002/bit.26462
Zhang CQ, Seow VY, Chen XX, Too HP (2018b) Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli. Nat Commun 9(1):1858. https://doi.org/10.1038/s41467-018-04211-x
Zhou L, Ding Q, Jiang GZ, Liu ZN, Wang HY, Zhao GR (2017a) Chromosome engineering of Escherichia coli for constitutive production of salvianic acid A. Microb Cell Factories 16(1):84. https://doi.org/10.1186/s12934-017-0700-2
Zhou SH, Du GC, Kang Z, Li JH, Chen J, Li HZ, Zhou JW (2017b) The application of powerful promoters to enhance gene expression in industrial microorganisms. World J Microbiol Biotechnol 33(2):23–10. https://doi.org/10.1007/s11274-016-2184-3
Funding
This work was funded by National Natural Science Foundation of China (Grant No. 21602199).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Jin, LQ., Jin, WR., Ma, ZC. et al. Promoter engineering strategies for the overproduction of valuable metabolites in microbes. Appl Microbiol Biotechnol 103, 8725–8736 (2019). https://doi.org/10.1007/s00253-019-10172-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-019-10172-y