Skip to main content

Gene Expression Engineering

  • Chapter
  • First Online:
Metabolic Engineering for Bioprocess Commercialization

Abstract

Cellular systems can become platforms for chemical production. Over the last four years, over 50 biopharmaceuticals have been approved for production, ranging in scope from hormones, enzymes, fusion proteins, antibodies, and vaccines. However, each of these applications—whether chemicals or pharmaceuticals, requires both a host organism and tools to engineer pathways in this chosen organism. The cellular hosts for these processes range in scope and complexity to include bacterial systems like Escherichia coli, yeast systems like Saccharomyces cerevisiae, and a variety of mammalian cell systems. To accomplish these production goals, it is necessary to control gene expression (especially of heterologous genes and pathways). This chapter will evaluate methods for controlling gene expression in the context of heterologous genes, endogenous genes, pathway expression and provide insight into new paradigms for flux control through gene expression circuits. A focus of this chapter will be on the various synthetic tools available for gene expression control. Although these basic principles are broadly applicable to multiple organisms, the predominant focus of this chapter will be on microbial systems, particularly E. coli and S. cerevisiae.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe H, Aiba H (1996) Differential contributions of two elements of rho-independent terminator to transcription termination and mRNA stabilization. Biochimie 78(11–12):1035–1042

    Article  CAS  PubMed  Google Scholar 

  • Adams BG (1972) Induction of galactokinase in Saccharomyces cerevisiae: kinetics of induction and glucose effects. J Bacteriol 111(2):308–315

    CAS  PubMed  PubMed Central  Google Scholar 

  • Agnew DE, Pfleger BF (2011) Optimization of synthetic operons using libraries of post-transcriptional regulatory elements. Methods Mol Biol 765:99–111

    Article  CAS  PubMed  Google Scholar 

  • Ajikumar PK et al (2010) Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330(6000):70–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alper H et al (2005) Tuning genetic control through promoter engineering. Proc Natl Acad Sci USA 102(36):12678–12683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amit R (2012) Towards synthetic gene circuits with enhancers: biology’s multi-input integrators. Subcell Biochem 64:3–20

    Article  CAS  PubMed  Google Scholar 

  • Anthony JR et al (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene. Metab Eng 11(1):13–19

    Article  CAS  PubMed  Google Scholar 

  • Atkinson MR et al (2003) Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli. Cell 113(5):597–607

    Article  CAS  PubMed  Google Scholar 

  • Baneyx F (1999) Recombinant protein expression in Escherichia coli. Curr Opin Biotechnol 10(5):411–421

    Article  CAS  PubMed  Google Scholar 

  • Bassel J, Mortimer R (1971) Genetic order of the galactose structural genes in Saccharomyces cerevisiae. J Bacteriol 108(1):179–183

    CAS  PubMed  PubMed Central  Google Scholar 

  • Batard Y et al (2000) Increasing expression of P450 and P450-reductase proteins from monocots in heterologous systems. Arch Biochem Biophys 379(1):161–169

    Article  CAS  PubMed  Google Scholar 

  • Berlec A, Strukelj B (2013) Current state and recent advances in biopharmaceutical production in Escherichia coli, yeasts and mammalian cells. J Ind Microbiol Biotechnol 40(3–4):257–274

    Article  CAS  PubMed  Google Scholar 

  • Blazeck J, Alper HS (2013) Promoter engineering: recent advances in controlling transcription at the most fundamental level. Biotechnol J 8(1):46–58

    Article  CAS  PubMed  Google Scholar 

  • Blazeck J et al (2011) Tuning gene expression in Yarrowia lipolytica by a hybrid promoter approach. Appl Environ Microbiol 77(22):7905–7914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blazeck J et al (2012) Controlling promoter strength and regulation in Saccharomyces cerevisiae using synthetic hybrid promoters. Biotechnol Bioeng 109(11):2884–2895

    Article  CAS  PubMed  Google Scholar 

  • Blazeck J et al (2014a) Metabolic engineering of Saccharomyces cerevisiae for itaconic acid production. Appl Microbiol Biotechnol 98(19):8155–8164

    Article  CAS  PubMed  Google Scholar 

  • Blazeck J et al (2014b) Harnessing Yarrowia lipolytica lipogenesis to create a platform for lipid and biofuel production. Nat Commun 5:3131

    Article  PubMed  CAS  Google Scholar 

  • Bolivar F et al (1976) Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene 2(2):95–113

    Google Scholar 

  • Brophy JA, Voigt CA (2014) Principles of genetic circuit design. Nat Methods 11(5):508–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cambray G et al (2013) Measurement and modeling of intrinsic transcription terminators. Nucleic Acids Res 41(9):5139–5148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camps M (2009) Modulation of ColE1-like plasmid replication for recombinant gene expression. Recent Pat DNA Gene Sequences 4(1):58–73

    Article  Google Scholar 

  • Celik E, Calik P (2012) Production of recombinant proteins by yeast cells. Biotechnol Adv 30(5):1108–1118

    Article  CAS  PubMed  Google Scholar 

  • Chang AC, Cohen SN (1978) Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid. J Bacteriol 134(3):1141–1156

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chao YP, Wen CS, Wang JY (2004) A facile and efficient method to achieve LacZ overproduction by the expression vector carrying the thermoregulated promoter and plasmid copy number. Biotechnol Prog 20(2):420–425

    Article  CAS  PubMed  Google Scholar 

  • Chen R (2012) Bacterial expression systems for recombinant protein production: E. coli and beyond. Biotechnol Adv 30(5):1102–1107

    Article  CAS  PubMed  Google Scholar 

  • Chen D, Arkin AP (2012) Sequestration-based bistability enables tuning of the switching boundaries and design of a latch. Mol Syst Biol 8:620

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen X et al (2013) Metabolic engineering of Escherichia coli: a sustainable industrial platform for bio-based chemical production. Biotechnol Adv 31(8):1200–1223

    Article  CAS  PubMed  Google Scholar 

  • Cherest H, Kerjan P, Surdin-Kerjan Y (1987) The Saccharomyces cerevisiae MET3 gene: nucleotide sequence and relationship of the 5’ non-coding region to that of MET25. Molecular & general genetics: MGG 210(2):307–313

    Article  CAS  Google Scholar 

  • Chou CP (2007) Engineering cell physiology to enhance recombinant protein production in Escherichia coli. Appl Microbiol Biotechnol 76(3):521–532

    Article  CAS  PubMed  Google Scholar 

  • Cigan AM, Pabich EK, Donahue TF (1988) Mutational analysis of the HIS4 translational initiator region in Saccharomyces cerevisiae. Mol Cell Biol 8(7):2964–2975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clarke L, Carbon J (1980) Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature 287(5782):504–509

    Article  CAS  PubMed  Google Scholar 

  • Crook NC, Schmitz AC, Alper HS (2014) Optimization of a yeast RNA interference system for controlling gene expression and enabling rapid metabolic engineering. ACS Synth Biol 3(5):307–313

    Article  CAS  PubMed  Google Scholar 

  • Curran KA et al (2013a) Metabolic engineering of muconic acid production in Saccharomyces cerevisiae. Metab Eng 15:55–66

    Article  CAS  PubMed  Google Scholar 

  • Curran KA et al (2013b) Use of expression-enhancing terminators in Saccharomyces cerevisiae to increase mRNA half-life and improve gene expression control for metabolic engineering applications. Metab Eng 19:88–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curran KA et al (2014) Design of synthetic yeast promoters via tuning of nucleosome architecture. Nat Commun 5:4002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Curry KA, Tomich CS (1988) Effect of ribosome binding site on gene expression in Escherichia coli. DNA 7(3):173–179

    Article  CAS  PubMed  Google Scholar 

  • Da Silva NA, Srikrishnan S (2012) Introduction and expression of genes for metabolic engineering applications in Saccharomyces cerevisiae. FEMS Yeast Res 12(2):197–214

    Article  PubMed  CAS  Google Scholar 

  • Dalton AC, Barton WA (2014) Over-expression of secreted proteins from mammalian cell lines. Protein Sci 23(5):517–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Datsenko KA, Wanner BL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 97(12):6640–6645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dehli T, Solem C, Jensen PR (2012) Tunable promoters in synthetic and systems biology. Subcell Biochem 64:181–201

    Article  CAS  PubMed  Google Scholar 

  • del Solar G, Espinosa M (2000) Plasmid copy number control: an ever-growing story. Mol Microbiol 37(3):492–500

    Article  PubMed  Google Scholar 

  • del Solar G et al (1998) Replication and control of circular bacterial plasmids. Microbiol Mol Biol Rev 62(2):434–464

    PubMed  PubMed Central  Google Scholar 

  • DiCarlo JE et al (2013) Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems. Nucleic Acids Res 41(7):4336–4343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Ellefson JW et al (2014) Directed evolution of genetic parts and circuits by compartmentalized partnered replication. Nat Biotechnol 32(1):97–101

    Article  CAS  PubMed  Google Scholar 

  • Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403(6767):335–338

    Article  CAS  PubMed  Google Scholar 

  • Feklistov A (2013) RNA polymerase: in search of promoters. Ann N Y Acad Sci 1293:25–32

    Article  CAS  PubMed  Google Scholar 

  • Fung E et al (2005) A synthetic gene-metabolic oscillator. Nature 435(7038):118–122

    Article  CAS  PubMed  Google Scholar 

  • Futcher B, Carbon J (1986) Toxic effects of excess cloned centromeres. Mol Cell Biol 6(6):2213–2222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gardner TS, Cantor CR, Collins JJ (2000) Construction of a genetic toggle switch in Escherichia coli. Nature 403(6767):339–342

    Article  CAS  PubMed  Google Scholar 

  • Genbauffe FS, Chisholm GE, Cooper TG (1984) Tau, sigma, and delta. A family of repeated elements in yeast. J Biol Chem 259(16):10518–10525

    CAS  PubMed  Google Scholar 

  • Giaever G, Nislow C (2014) The yeast deletion collection: a decade of functional genomics. Genetics 197(2):451–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giaever G et al (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418(6896):387–391

    Article  CAS  PubMed  Google Scholar 

  • Goh S, Good L (2008) Plasmid selection in Escherichia coli using an endogenous essential gene marker. BMC Biotechnol 8:61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gorgoni B et al (2014) Controlling translation elongation efficiency: tRNA regulation of ribosome flux on the mRNA. Biochem Soc Trans 42(1):160–165

    Article  CAS  PubMed  Google Scholar 

  • Graumann K, Premstaller A (2006) Manufacturing of recombinant therapeutic proteins in microbial systems. Biotechnol J 1(2):164–186

    Article  CAS  PubMed  Google Scholar 

  • Gustafsson C, Govindarajan S, Minshull J (2004) Codon bias and heterologous protein expression. Trends Biotechnol 22(7):346–353

    Article  CAS  PubMed  Google Scholar 

  • Guzman LM et al (1995) Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol 177(14):4121–4130

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hägg P et al (2004) A host/plasmid system that is not dependent on antibiotics and antibiotic resistance genes for stable plasmid maintenance in Escherichia coli. J Biotechnol 111(1):17–30

    Article  PubMed  CAS  Google Scholar 

  • Hamilton R, Watanabe CK, de Boer HA (1987) Compilation and comparison of the sequence context around the AUG startcodons in Saccharomyces cerevisiae mRNAs. Nucleic Acids Res 15(8):3581–3593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrison ME, Dunlop MJ (2012) Synthetic feedback loop model for increasing microbial biofuel production using a biosensor. Front Microbiol 3:360

    Article  PubMed  PubMed Central  Google Scholar 

  • Holladay JE et al (2007) Top value-added chemicals from biomass: results of screening for potential candidates from biorefinery lignin. Pacific Northwest National Laboratory

    Google Scholar 

  • Holtz WJ, Keasling JD (2010) Engineering static and dynamic control of synthetic pathways. Cell 140(1):19–23

    Article  CAS  PubMed  Google Scholar 

  • Ito Y et al (2013) Characterization of five terminator regions that increase the protein yield of a transgene in Saccharomyces cerevisiae. J Biotechnol 168(4):486–492

    Article  CAS  PubMed  Google Scholar 

  • Jackson RJ, Hellen CU, Pestova TV (2010) The mechanism of eukaryotic translation initiation and principles of its regulation. Nat Rev Mol Cell Biol 11(2):113–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang W et al (2013) RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol 31(3):233–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnston M (1987) A model fungal gene regulatory mechanism: the GAL genes of Saccharomyces cerevisiae. Microbiol Rev 51(4):458–476

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jones KL, Kim SW, Keasling JD (2000) Low-copy plasmids can perform as well as or better than high-copy plasmids for metabolic engineering of bacteria. Metab Eng 2(4):328–338

    Article  CAS  PubMed  Google Scholar 

  • Kane JF (1995) Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli. Curr Opin Biotechnol 6(5):494–500

    Article  CAS  PubMed  Google Scholar 

  • Karim AS, Curran KA, Alper HS (2013) Characterization of plasmid burden and copy number in Saccharomyces cerevisiae for optimization of metabolic engineering applications. FEMS Yeast Res 13(1):107–116

    Article  CAS  PubMed  Google Scholar 

  • Kobori S et al (2013) A controllable gene expression system in liposomes that includes a positive feedback loop. Mol BioSyst 9(6):1282–1285

    Article  CAS  PubMed  Google Scholar 

  • Kozak M (2002) Pushing the limits of the scanning mechanism for initiation of translation. Gene 299(1–2):1–34

    Article  CAS  PubMed  Google Scholar 

  • Kroll J et al (2009) Establishment of a novel anabolism-based addiction system with an artificially introduced mevalonate pathway: Complete stabilization of plasmids as universal application in white biotechnology. Metab Eng 11(3):168–177

    Article  CAS  PubMed  Google Scholar 

  • Kroll J et al (2010) Plasmid addiction systems: perspectives and applications in biotechnology. Microb Biotechnol 3(6):634–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kroll J, Klinter S, Steinbuchel A (2011) A novel plasmid addiction system for large-scale production of cyanophycin in Escherichia coli using mineral salts medium. Appl Microbiol Biotechnol 89(3):593–604

    Article  CAS  PubMed  Google Scholar 

  • Labbe S, Thiele DJ (1999) Copper ion inducible and repressible promoter systems in yeast. Methods Enzymol 306:145–153

    Article  CAS  PubMed  Google Scholar 

  • Lee C et al (2006) Absolute and relative QPCR quantification of plasmid copy number in Escherichia coli. J Biotechnol 123(3):273–280

    Article  CAS  PubMed  Google Scholar 

  • Levin-Karp A et al (2013) Quantifying translational coupling in E. coli synthetic operons using RBS modulation and fluorescent reporters. ACS Synth. Biol 2(6):327–336

    CAS  Google Scholar 

  • Lewis M (2005) The lac repressor. C R Biol 328(6):521–548

    Article  CAS  PubMed  Google Scholar 

  • Lewis M (2011) A tale of two repressors. J Mol Biol 409(1):14–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z et al (2013) Direct and efficient xylitol production from xylan by Saccharomyces cerevisiae through transcriptional level and fermentation processing optimizations. Bioresour Technol 149:413–419

    Article  CAS  PubMed  Google Scholar 

  • Liang S et al (1999) Activities of constitutive promoters in Escherichia coli. J Mol Biol 292(1):19–37

    Article  CAS  PubMed  Google Scholar 

  • Lim HN, Lee Y, Hussein R (2011) Fundamental relationship between operon organization and gene expression. Proc Natl Acad Sci USA 108(26):10626–10631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L et al (2013a) How to achieve high-level expression of microbial enzymes: strategies and perspectives. Bioengineered 4(4):212–223

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu L, Redden H, Alper HS (2013b) Frontiers of yeast metabolic engineering: diversifying beyond ethanol and Saccharomyces. Curr Opin Biotechnol 24(6):1023–1030

    Article  CAS  PubMed  Google Scholar 

  • Lu WC, Ellington AD (2014) Design and selection of a synthetic operon. ACS Synth Biol 3(6):410–415

    Article  CAS  PubMed  Google Scholar 

  • Madyagol M et al (2011) Gene replacement techniques for Escherichia coli genome modification. Folia Microbiol (Praha) 56(3):253–263

    Article  CAS  Google Scholar 

  • Makoff AJ, Oxer MD (1991) High level heterologous expression in E. coli using mutant forms of the lac promoter. Nucleic Acids Res 19(9):2417–2421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Makrides SC (1996) Strategies for achieving high-level expression of genes in Escherichia coli. Microbiol Rev 60(3):512–538

    CAS  PubMed  PubMed Central  Google Scholar 

  • Malys N (2012) Shine-Dalgarno sequence of bacteriophage T4: GAGG prevails in early genes. Mol Biol Rep 39(1):33–39

    Article  CAS  PubMed  Google Scholar 

  • Martinez JL et al (2012) Pharmaceutical protein production by yeast: towards production of human blood proteins by microbial fermentation. Curr Opin Biotechnol 23(6):965–971

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto Y et al (2011) Bacterial cells carrying synthetic dual-function operon survived starvation. J Biomed Biotechnol 2011:489265

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mead DJ, Gardner DC, Oliver SG (1986) The yeast 2 micron plasmid: strategies for the survival of a selfish DNA. Mol Gen Genet 205(3):417–421

    Article  CAS  PubMed  Google Scholar 

  • Mieschendahl M, Petri T, Hanggi U (1986) A Novel prophage independent Trp regulated lambda-Pl expression system. Bio-Technology 4(9):802–809

    Article  CAS  Google Scholar 

  • Minton NP (1984) Improved plasmid vectors for the isolation of translational lac gene fusions. Gene 31(1–3):269–273

    Article  CAS  PubMed  Google Scholar 

  • Morris MK et al (2010) Logic-based models for the analysis of cell signaling networks. Biochemistry 49(15):3216–3224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muller PP, Trachsel H (1990) Translation and regulation of translation in the yeast Saccharomyces cerevisiae. Eur J Biochem 191(2):257–261

    Article  CAS  PubMed  Google Scholar 

  • Mumberg D, Muller R, Funk M (1995) Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds. Gene 156(1):119–122

    Article  CAS  PubMed  Google Scholar 

  • Nevoigt E et al (2006) Engineering of promoter replacement cassettes for fine-tuning of gene expression in Saccharomyces cerevisiae. Appl Environ Microbiol 72(8):5266–5273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nevoigt E et al (2007) Engineering promoter regulation. Biotechnol Bioeng 96(3):550–558

    Article  CAS  PubMed  Google Scholar 

  • Nielsen J (2013) Production of biopharmaceutical proteins by yeast: advances through metabolic engineering. Bioengineered 4(4):207–211

    Article  PubMed  Google Scholar 

  • Nielsen AA et al (2016) Genetic circuit design automation. Science 352(6281):aac7341

    Google Scholar 

  • Nordstrom K (2006) Plasmid R1–replication and its control. Plasmid 55(1):1–26

    Article  PubMed  CAS  Google Scholar 

  • Okuda S et al (2007) Characterization of relationships between transcriptional units and operon structures in Bacillus subtilis and Escherichia coli. BMC Genom 8:48

    Article  Google Scholar 

  • Partow S et al (2010) Characterization of different promoters for designing a new expression vector in Saccharomyces cerevisiae. Yeast 27(11):955–964

    Article  CAS  PubMed  Google Scholar 

  • Peubez I et al (2010) Antibiotic-free selection in E. coli: new considerations for optimal design and improved production. Microb Cell Fact 9:65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Price VL et al (1990) Expression of heterologous proteins in Saccharomyces cerevisiae using the ADH2 promoter. Methods Enzymol 185:308–318

    Article  CAS  PubMed  Google Scholar 

  • Rajkumar AS, Maerkl SJ (2012) Rapid synthesis of defined eukaryotic promoter libraries. ACS Synth Biol 1(10):483–490

    Article  CAS  PubMed  Google Scholar 

  • Ramalingam KI et al (2009) Forward engineering of synthetic bio-logical AND gates. Biochem Eng J 47(1–3):38–47

    Article  CAS  Google Scholar 

  • Redden H, Alper HS (2015) The development and characterization of synthetic minimal yeast promoters. Nat Commun 6:7810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Redden H, Morse N, Alper HS (2014) The synthetic biology toolbox for tuning gene expression in yeast. FEMS Yeast Res

    Google Scholar 

  • Ro DK et al (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440(7086):7940–7943

    Article  CAS  Google Scholar 

  • Rosano GL, Ceccarelli EA (2014) Recombinant protein expression in Escherichia coli: advances and challenges. Front Microbiol 5:172

    PubMed  PubMed Central  Google Scholar 

  • Salis HM (2011) The ribosome binding site calculator. Methods Enzymol 498:19–42

    Article  CAS  PubMed  Google Scholar 

  • Sanchez S, Demain A (2012) Special issue on the production of recombinant proteins. Biotechnol Adv 30(5):1100–1101

    Article  PubMed  Google Scholar 

  • Sander JD, Joung JK (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 32(4):347–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sangsoda S, Cherest H, Surdin-Kerjan Y (1984) The expression of the MET25 gene of Saccharomyces cerevisiae is regulated transcriptionally. Molecular & general genetics: MGG 200(3):407–414

    Article  Google Scholar 

  • Sauer B (1987) Functional expression of the cre-lox site-specific recombination system in the yeast Saccharomyces cerevisiae. Mol Cell Biol 7(6):2087–2096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah P et al (2013) Rate-limiting steps in yeast protein translation. Cell 153(7):1589–1601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shine J, Dalgarno L (1975) Determinant of cistron specificity in bacterial ribosomes. Nature 254(5495):34–38

    Article  CAS  PubMed  Google Scholar 

  • Silva-Rocha R, de Lorenzo V (2014) Chromosomal integration of transcriptional fusions. Methods Mol Biol 1149:479–489

    Article  CAS  PubMed  Google Scholar 

  • Silverstone AE, Arditti RR, Magasanik B (1970) Catabolite-insensitive revertants of lac promoter mutants. Proc Natl Acad Sci U S A 66(3):773–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh V (2014) Recent advancements in synthetic biology: current status and challenges. Gene 535(1):1–11

    Article  CAS  PubMed  Google Scholar 

  • Sorensen HP, Mortensen KK (2005) Advanced genetic strategies for recombinant protein expression in Escherichia coli. J Biotechnol 115(2):113–128

    Article  CAS  PubMed  Google Scholar 

  • Stoker NG, Fairweather NF, Spratt BG (1982) Versatile low-copy-number plasmid vectors for cloning in Escherichia coli. Gene 18(3):335–341

    Article  CAS  PubMed  Google Scholar 

  • Stricker J et al (2008) A fast, robust and tunable synthetic gene oscillator. Nature 456(7221):516–519

    Article  CAS  PubMed  Google Scholar 

  • Suess B et al (2012) Aptamer-regulated expression of essential genes in yeast. Methods Mol Biol 824:381–391

    Article  CAS  PubMed  Google Scholar 

  • Sun J et al (2012) Cloning and characterization of a panel of constitutive promoters for applications in pathway engineering in Saccharomyces cerevisiae. Biotechnol Bioeng 109(8):2082–2092

    Article  CAS  PubMed  Google Scholar 

  • Taxis C, Knop M (2006) System of centromeric, episomal, and integrative vectors based on drug resistance markers for Saccharomyces cerevisiae. Biotechniques 40(1):73–78

    Article  CAS  PubMed  Google Scholar 

  • Temme K, Zhao D, Voigt CA (2012) Refactoring the nitrogen fixation gene cluster from Klebsiella oxytoca. Proc Natl Acad Sci U S A 109(18):7085–7090

    Article  PubMed  PubMed Central  Google Scholar 

  • Terpe K (2006) Overview of bacterial expression systems for heterologous protein production: from molecular and biochemical fundamentals to commercial systems. Appl Microbiol Biotechnol 72(2):211–222

    Article  CAS  PubMed  Google Scholar 

  • Voss I, Steinbuchel A (2006) Application of a KDPG-aldolase gene-dependent addiction system for enhanced production of cyanophycin in Ralstonia eutropha strain H16. Metab Eng 8(1):66–78

    Article  CAS  PubMed  Google Scholar 

  • Walsh G (2010) Biopharmaceutical benchmarks 2010. Nat Biotechnol 28(9):917–924

    Article  CAS  PubMed  Google Scholar 

  • Walsh G (2014) Biopharmaceutical benchmarks 2014. Nat Biotechnol 32(10):992–1000

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Buck M (2012) Customizing cell signaling using engineered genetic logic circuits. Trends Microbiol 20(8):376–384

    Article  PubMed  CAS  Google Scholar 

  • Wang RF, Kushner SR (1991) Construction of versatile low-copy-number vectors for cloning, sequencing and gene expression in Escherichia coli. Gene 100:195–199

    Article  CAS  PubMed  Google Scholar 

  • Wang SH, Shih YH, Lin LY (1998) Yeast consensus initiator sequence markedly enhances the synthesis of metallothionein III in Saccharomyces cerevisiae. Biotechnol Lett 20(1):9–13

    Article  Google Scholar 

  • Wang Z et al (2012) Expression and production of recombinant cis-epoxysuccinate hydrolase in Escherichia coli under the control of temperature-dependent promoter. J Biotechnol 162(2–3):232–236

    Article  CAS  PubMed  Google Scholar 

  • Welch M et al (2009) You’re one in a googol: optimizing genes for protein expression. J R Soc Interface 6(Suppl 4):S467–S476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Werpy T et al (2004) Top value added chemicals from biomass: results of screening for potential candidates from sugars and synthesis gas. [U.S. Department of Energy [Office of] Energy Efficiency and Renewable Energy

    Google Scholar 

  • Westfall PJ et al (2012) Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proc Natl Acad Sci U S A 109(3):E111–E118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winzeler EA et al (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285(5429):5901–5906

    Article  Google Scholar 

  • Wu X et al (2014) Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. Nat Biotechnol 32(7):670–676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanishi M, Katahira S, Matsuyama T (2011) TPS1 terminator increases mRNA and protein yield in a Saccharomyces cerevisiae expression system. Biosci Biotechnol Biochem 75(11):2234–2236

    Article  CAS  PubMed  Google Scholar 

  • Yamanishi M et al (2013) A genome-wide activity assessment of terminator regions in Saccharomyces cerevisiae provides a “terminatome” toolbox. ACS Synth Biol 2(6):337–347

    Article  CAS  PubMed  Google Scholar 

  • Yao YF et al (2013) Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway. Metab Eng 19:79–87

    Article  CAS  PubMed  Google Scholar 

  • Yokobayashi Y, Weiss R, Arnold FH (2002) Directed evolution of a genetic circuit. Proc Natl Acad Sci USA 99(26):16587–16591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoon H, Donahue TF (1992) Control of translation initiation in Saccharomyces cerevisiae. Mol Microbiol 6(11):1413–1419

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, 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

    Article  CAS  PubMed  Google Scholar 

  • Zhu J (2012) Mammalian cell protein expression for biopharmaceutical production. Biotechnol Adv 30(5):1158–1170

    Article  CAS  PubMed  Google Scholar 

  • Zielenkiewicz U, CegĹ‚owski P (2001) Mechanisms of plasmid stable maintenance with special focus on plasmid addiction systems. Acta Biochim Pol 48(4):1003–1023

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hal S. Alper .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Morse, N.J., Alper, H.S. (2016). Gene Expression Engineering. In: Van Dien, S. (eds) Metabolic Engineering for Bioprocess Commercialization. Springer, Cham. https://doi.org/10.1007/978-3-319-41966-4_2

Download citation

Publish with us

Policies and ethics