Skip to main content
SpringerLink
Log in

Efflux systems in bacteria and their metabolic engineering applications

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

The production of valuable chemicals from metabolically engineered microbes can be limited by excretion from the cell. Efflux is often overlooked as a bottleneck in metabolic pathways, despite its impact on alleviating feedback inhibition and product toxicity. In the past, it has been assumed that endogenous efflux pumps and membrane porins can accommodate product efflux rates; however, there are an increasing number of examples wherein overexpressing efflux systems is required to improve metabolite production. In this review, we highlight specific examples from the literature where metabolite export has been studied to identify unknown transporters, increase tolerance to metabolites, and improve the production capabilities of engineered bacteria. The review focuses on the export of a broad spectrum of valuable chemicals including amino acids, sugars, flavins, biofuels, and solvents. The combined set of examples supports the hypothesis that efflux systems can be identified and engineered to confer export capabilities on industrially relevant microbes.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ajinomoto (2013) Feed-use amino acids business. http://www.ajinomoto.com/en/ir/pdf/Feed-useAA-Oct2013.pdf.

  • Alonso-Gutierrez J, Chan R, Batth TS, Adams PD, Keasling JD, Petzold CJ, Lee TS (2013) Metabolic engineering of Escherichia coli for limonene and perillyl alcohol production. Metab Eng 19:33–41

    Article  CAS  PubMed  Google Scholar 

  • Bass RB, Strop P, Barclay M, Rees DC (2002) Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel. Science 298:1582–1587

    Article  CAS  PubMed  Google Scholar 

  • Belitsky BR, Gustafsson MC, Sonenshein AL, Von Wachenfeldt C (1997) An lrp-like gene of Bacillus subtilis involved in branched-chain amino acid transport. J Bacteriol 179:5448–5457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bellmann A, Vrljic M, Patek M, Sahm H, Kramer R, Eggeling L (2001) Expression control and specificity of the basic amino acid exporter LysE of Corynebacterium glutamicum. Microbiology 147:1765–1774

    Article  CAS  PubMed  Google Scholar 

  • Bernal P, Segura A, Ramos JL (2007) Compensatory role of the cis-trans-isomerase and cardiolipin synthase in the membrane fluidity of Pseudomonas putida DOT-T1E. Environ Microbiol 9:1658–1664

    Article  CAS  PubMed  Google Scholar 

  • Blank LM, Ionidis G, Ebert BE, Buhler B, Schmid A (2008) Metabolic response of Pseudomonas putida during redox biocatalysis in the presence of a second octanol phase. FEBS J 275:5173–5190

    Article  CAS  PubMed  Google Scholar 

  • Borngen K, Battle AR, Moker N, Morbach S, Marin K, Martinac B, Kramer R (2010) The properties and contribution of the Corynebacterium glutamicum MscS variant to fine-tuning of osmotic adaptation. Biochim Biophys Acta 1798:2141–2149

    Article  PubMed  CAS  Google Scholar 

  • Bost S, Silva F, Belin D (1999) Transcriptional activation of ydeA, which encodes a member of the major facilitator superfamily, interferes with arabinose accumulation and induction of the Escherichia coli arabinose PBAD promoter. J Bacteriol 181:2185–2191

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brown LM, Gunasekera TS, Ruiz ON (2014) Draft genome sequence of Pseudomonas aeruginosa ATCC 33988, a bacterium highly adapted to fuel-polluted environments. Genome Announc 2:e01113–e01114

    PubMed  PubMed Central  Google Scholar 

  • Burkovski A, Kramer R (2002) Bacterial amino acid transport proteins: occurrence, functions, and significance for biotechnological applications. Appl Microbiol Biot 58:265–274

    Article  CAS  Google Scholar 

  • Carole S, Pichoff S, Bouch JP (1999) Escherichia coli gene ydeA encodes a major facilitator pump which exports L-arabinose and isopropyl-beta-D-thiogalactopyranoside. J Bacteriol 181:5123–5125

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen C, Li Y, Hu J, Dong X, Wang X (2015) Metabolic engineering of Corynebacterium glutamicum ATCC13869 for l-valine production. Metab Eng 29:66–75

    Article  PubMed  CAS  Google Scholar 

  • Dassler T, Maier T, Winterhalter C, Bock A (2000) Identification of a major facilitator protein from Escherichia coli involved in efflux of metabolites of the cysteine pathway. Mol Microbiol 36:1101–1112

    Article  CAS  PubMed  Google Scholar 

  • Debabov V, Kozlov J, Khurges E, Livshits V, Zhadanova N, Gusyativer M, Sokolov A, Bacchina T (1997) Bacterial strain of Escherichia coli VNII Genetika 472T23 as the producer of L-threonine. US Patent 5,631,157 Ajinomoto Co., Tokyo, Japan

    Google Scholar 

  • Demain AL, Birnbaum J (1968) Alteration of permeability for the release of metabolites from the microbial cell. Curr Top Microbiol Immunol 46:1–25

    CAS  PubMed  Google Scholar 

  • Dmytruk KV, Sibirny AA (2012) Candida famata (Candida flareri). Yeast 29:453–458

    Article  CAS  PubMed  Google Scholar 

  • Dong X, Quinn PJ, Wang X (2011) Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the production of L-threonine. Biotechnol Adv 29:11–23

    Article  CAS  PubMed  Google Scholar 

  • Doroshenko V, Airich L, Vitushkina M, Kolokolova A, Livshits V, Mashko S (2007) YddG from Escherichia coli promotes export of aromatic amino acids. FEMS Microbiol Lett 275:312–318

    Article  CAS  PubMed  Google Scholar 

  • Doshi R, Nguyen T, Chang G (2013) Transporter-mediated biofuel secretion. Proc Natl Acad Sci U S A 110:7642–7647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du D, van Veen HW, Luisi BF (2015) Assembly and operation of bacterial tripartite multidrug efflux pumps. Trends Microbiol 23:311–319

    Article  CAS  PubMed  Google Scholar 

  • Ducat DC, Avelar-Rivas JA, Way JC, Silver PA (2012) Rerouting carbon flux to enhance photosynthetic productivity. Appl Environ Microb 78:2660–2668

    Article  CAS  Google Scholar 

  • Dunlop MJ, Dossani ZY, Szmidt HL, Chu HC, Lee TS, Keasling JD, Hadi MZ, Mukhopadhyay A (2011) Engineering microbial biofuel tolerance and export using efflux pumps. Mol Syst Biol 7:487

    Article  PubMed  PubMed Central  Google Scholar 

  • Eggeling L, Sahm H (2003) New ubiquitous translocators: amino acid export by Corynebacterium glutamicum and Escherichia coli. Arch Microbiology 180:155–160

    Article  CAS  Google Scholar 

  • Eggeling L, Krumbach K, Sahm H (2001) L-glutamate efflux with Corynebacterium glutamicum: why is penicillin treatment or Tween addition doing the same? J Mol Microbiol Biotechnol 3:67–68

    CAS  PubMed  Google Scholar 

  • Faizal I, Dozen K, Hong CS, Kuroda A, Takiguchi N, Ohtake H, Takeda K, Tsunekawa H, Kato J (2005) Isolation and characterization of solvent-tolerant Pseudomonas putida strain T-57, and its application to biotransformation of toluene to cresol in a two-phase (organic-aqueous) system. J Ind Microbiol Biot 32:542–547

    Article  CAS  Google Scholar 

  • Fillet S, Daniels C, Pini C, Krell T, Duque E, Bernal P, Segura A, Lu D, Zhang X, Ramos JL (2012) Transcriptional control of the main aromatic hydrocarbon efflux pump in Pseudomonas. Environ Microbiol Rep 4:158–167

    Article  CAS  PubMed  Google Scholar 

  • Fisher MA, Boyarskiy S, Yamada MR, Kong N, Bauer S, Tullman-Ercek D (2014) Enhancing tolerance to short-chain alcohols by engineering the Escherichia coli AcrB efflux pump to secrete the non-native substrate n-butanol. ACS Synth Biol 3:30–40

    Article  CAS  PubMed  Google Scholar 

  • Foo JL, Leong SS (2013) Directed evolution of an E. coli inner membrane transporter for improved efflux of biofuel molecules. Biotechnol Biofuels 6:81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franke I, Resch A, Dassler T, Maier T, Bock A (2003) YfiK from Escherichia coli promotes export of O-acetylserine and cysteine. J Bacteriol 185:1161–1166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ginesy M, Belotserkovsky J, Enman J, Isaksson L, Rova U (2015) Metabolic engineering of Escherichia coli for enhanced arginine biosynthesis. Microb Cell Fact 14:29

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Gunasekera TS, Striebich RC, Mueller SS, Strobel EM, Ruiz ON (2013) Transcriptional profiling suggests that multiple metabolic adaptations are required for effective proliferation of Pseudomonas aeruginosa in jet fuel. Environ Sci Technol 47:13449–13458

    Article  CAS  PubMed  Google Scholar 

  • Gutmann M, Hoischen C, Kramer R (1992) Carrier-mediated glutamate secretion by Corynebacterium glutamicum under biotin limitation. Biochim Biophys Acta 1112:115–123

    Article  CAS  PubMed  Google Scholar 

  • Harris CL (1981) Cysteine and growth inhibition of Escherichia coli: threonine deaminase as the target enzyme. J Bacteriol 145:1031–1035

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hashimoto K, Murata J, Konishi T, Yabe I, Nakamatsu T, Kawasaki H (2012) Glutamate is excreted across the cytoplasmic membrane through the NCgl1221 channel of Corynebacterium glutamicum by passive diffusion. Biosci Biotechnol Biochem 76:1422–1424

    Article  CAS  PubMed  Google Scholar 

  • He GX, Thorpe C, Walsh D, Crow R, Chen H, Kumar S, Varela MF (2011) EmmdR, a new member of the MATE family of multidrug transporters, extrudes quinolones from Enterobacter cloacae. Arch Microbiology 193:759–765

    Article  CAS  Google Scholar 

  • Hemamalini R, Khare S (2014) A proteomic approach to understand the role of the outer membrane porins in the organic solvent-tolerance of Pseudomonas aeruginosa PseA. PLoS One 9:e103788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemberger S, Pedrolli DB, Stolz J, Vogl C, Lehmann M, Mack M (2011) RibM from Streptomyces davawensis is a riboflavin/roseoflavin transporter and may be useful for the optimization of riboflavin production strains. BMC Biotechnol 11:119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirasawa T, Kim J, Shirai T, Furusawa C, Shimizu H (2012) Molecular mechanisms and metabolic engineering of glutamate overproduction in Corynebacterium glutamicum. Subcell Biochem 64:261–281

    Article  CAS  PubMed  Google Scholar 

  • Hoischen C, Kramer R (1990) Membrane alteration is necessary but not sufficient for effective glutamate secretion in Corynebacterium glutamicum. J Bacteriol 172:3409–3416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hori H, Ando T, Isogai E, Yoneyama H, Katsumata R (2011a) Identification of an L-alanine export system in Escherichia coli and isolation and characterization of export-deficient mutants. FEMS Microbiol Lett 316:83–89

    Article  CAS  PubMed  Google Scholar 

  • Hori H, Yoneyama H, Tobe R, Ando T, Isogai E, Katsumata R (2011b) Inducible L-alanine exporter encoded by the novel gene ygaW (alaE) in Escherichia coli. Appl Environ Microb 77:4027–4034

    Article  CAS  Google Scholar 

  • Huber RE, Lytton J, Fung EB (1980) Efflux of beta-galactosidase products from Escherichia coli. J Bacteriol 141:528–533

    CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue A, Horikoshi K (1989) A pseudomonas thrives in high-concentrations of toluene. Nature 338:264–266

    Article  CAS  Google Scholar 

  • Kang Z, Wang Y, Gu P, Wang Q, Qi Q (2011) Engineering Escherichia coli for efficient production of 5-aminolevulinic acid from glucose. Metab Eng 13:492–498

    Article  CAS  PubMed  Google Scholar 

  • Kennerknecht N, Sahm H, Yen MR, Patek M, Saier Jr MH Jr, Eggeling L (2002) Export of L-isoleucine from Corynebacterium glutamicum: a two-gene-encoded member of a new translocator family. J Bacteriol 184:3947–3956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim B, Park H, Na D, Lee SY (2014) Metabolic engineering of Escherichia coli for the production of phenol from glucose. Biotechnol J 9:621–629

    Article  CAS  PubMed  Google Scholar 

  • Kind S, Kreye S, Wittmann C (2011) Metabolic engineering of cellular transport for overproduction of the platform chemical 1,5-diaminopentane in Corynebacterium glutamicum. Metab Eng 13:617–627

    Article  CAS  PubMed  Google Scholar 

  • King G, Sharom FJ (2012) Proteins that bind and move lipids: MsbA and NPC1. Crit Rev Biochem Mol 47:75–95

    Article  CAS  Google Scholar 

  • Koita K, Rao CV (2012) Identification and analysis of the putative pentose sugar efflux transporters in Escherichia coli. PLoS One 7:e43700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kredich NM, Tomkins GM (1966) The enzymic synthesis of L-cysteine in Escherichia coli and Salmonella typhimurium. J Biol Chem 241:4955–4965

    CAS  PubMed  Google Scholar 

  • Kruse D, Kramer R, Eggeling L, Rieping M, Pfefferle W, Tchieu JH, Chung YJ Jr, Saier MH, Burkovski A (2002) Influence of threonine exporters on threonine production in Escherichia coli. Appl Microbiol Biot 59:205–210

    Article  CAS  Google Scholar 

  • Kutukova EA, Livshits VA, Altman IP, Ptitsyn LR, Zyiatdinov MH, Tokmakova IL, Zakataeva NP (2005) The yeaS (leuE) gene of Escherichia coli encodes an exporter of leucine, and the Lrp protein regulates its expression. FEBS Lett 579:4629–4634

    Article  CAS  PubMed  Google Scholar 

  • Lange C, Mustafi N, Frunzke J, Kennerknecht N, Wessel M, Bott M, Wendisch VF (2012) Lrp of Corynebacterium glutamicum controls expression of the brnFE operon encoding the export system for L-methionine and branched-chain amino acids. J Biotechnol 158:231–241

    Article  CAS  PubMed  Google Scholar 

  • Lee JH, Sung BH, Kim MS, Blattner FR, Yoon BH, Kim JH, Kim SC (2009) Metabolic engineering of a reduced-genome strain of Escherichia coli for L-threonine production. Microb Cell Fact 8:2

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lennen RM, Pfleger BF (2013) Microbial production of fatty acid-derived fuels and chemicals. Curr Opin Biotechnol 24:1044–1053

    Article  CAS  PubMed  Google Scholar 

  • Lennen RM, Politz MG, Kruziki MA, Pfleger BF (2013) Identification of transport proteins involved in free fatty acid efflux in Escherichia coli. J Bacteriol 195:135–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu JY, Miller PF, Gosink M, Olson ER (1999a) The identification of a new family of sugar efflux pumps in Escherichia coli. Mol Microbiol 31:1845–1851

    Article  CAS  PubMed  Google Scholar 

  • Liu JY, Miller PF, Willard J, Olson ER (1999b) Functional and biochemical characterization of Escherichia coli sugar efflux transporters. J Biol Chem 274:22977–22984

    Article  CAS  PubMed  Google Scholar 

  • Liu Q, Cheng Y, Xie X, Xu Q, Chen N (2012) Modification of tryptophan transport system and its impact on production of L-tryptophan in Escherichia coli. Bioresour Technol 114:549–554

    Article  CAS  PubMed  Google Scholar 

  • Livshits VA, Zakataeva NP, Aleshin VV, Vitushkina MV (2003) Identification and characterization of the new gene rhtA involved in threonine and homoserine efflux in Escherichia coli. Res Microbiol 154:123–135

    Article  CAS  PubMed  Google Scholar 

  • Martens J, Offermanns H, Scherberich P (1981) Facile synthesis of racemic cysteine. Angew Chem Int Edit 20:668

    Article  Google Scholar 

  • McAnulty MJ, Wood TK (2014) YeeO from Escherichia coli exports flavins. Bioengineered 5:386–392

    Article  PubMed  PubMed Central  Google Scholar 

  • Mingardon F, Clement C, Hirano K, Nhan M, Luning EG, Chanal A, Mukhopadhyay A (2015) Improving olefin tolerance and production in E. coli using native and evolved AcrB. Biotechnol Bioeng 112:879–888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mosqueda G, Ramos JL (2000) A set of genes encoding a second toluene efflux system in Pseudomonas putida DOT-T1E is linked to the tod genes for toluene metabolism. J Bacteriol 182:937–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mulder KC, Bandola J, Schumann W (2013) Construction of an artificial secYEG operon allowing high level secretion of alpha-amylase. Protein Expr Purif 89:92–96

  • Nakamura J, Hirano S, Ito H, Wachi M (2007) Mutations of the Corynebacterium glutamicum NCgl1221 gene, encoding a mechanosensitive channel homolog, induce L-glutamic acid production. Appl Environ Microb 73:4491–4498

    Article  CAS  Google Scholar 

  • Nandineni MR, Gowrishankar J (2004) Evidence for an arginine exporter encoded by yggA (argO) that is regulated by the LysR-type transcriptional regulator ArgP in Escherichia coli. J Bacteriol 186:3539–3546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nijkamp K, Westerhof RG, Ballerstedt H, de Bont JA, Wery J (2007) Optimization of the solvent-tolerant Pseudomonas putida S12 as host for the production of p-coumarate from glucose. Appl Microbiol Biot 74:617–624

    Article  CAS  Google Scholar 

  • Nikaido H, Pages JM (2012) Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev 36:340–363

    Article  CAS  PubMed  Google Scholar 

  • Oh HY, Lee JO, Kim OB (2012) Increase of organic solvent tolerance of Escherichia coli by the deletion of two regulator genes, fadR and marR. Appl Microbiol Biot 96:1619–1627

    Article  CAS  Google Scholar 

  • Ohtsu I, Wiriyathanawudhiwong N, Morigasaki S, Nakatani T, Kadokura H, Takagi H (2010) The L-cysteine/L-cystine shuttle system provides reducing equivalents to the periplasm in Escherichia coli. J Biol Chem 285:17479–17487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park S, Imlay JA (2003) High levels of intracellular cysteine promote oxidative DNA damage by driving the Fenton reaction. J Bacteriol 185:1942–1950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park JH, Lee SY (2010) Metabolic pathways and fermentative production of L-aspartate family amino acids. Biotechnol J 5:560–577

    Article  CAS  PubMed  Google Scholar 

  • Park JH, Lee KH, Kim TY, Lee SY (2007) Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation. Proc Natl Acad Sci U S A 104:7797–7802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park JH, Oh JE, Lee KH, Kim JY, Lee SY (2012) Rational design of Escherichia coli for L-isoleucine production. ACS Synth Biol 1:532–540

    Article  CAS  PubMed  Google Scholar 

  • Pathania A, Sardesai AA (2015) Distinct paths for basic amino acid export in Escherichia coli: YbjE (LysO) mediates export of l-lysine. J Bacteriol 197:2036–2047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peralta-Yahya PP, Zhang F, del Cardayre SB, Keasling JD (2012) Microbial engineering for the production of advanced biofuels. Nature 488:320–328

    Article  CAS  PubMed  Google Scholar 

  • Pfefferle W, Mockel B, Bathe B, Marx A (2003) Biotechnological manufacture of lysine. Adv Biochem Eng Biotechnol 79:59–112

    CAS  PubMed  Google Scholar 

  • Pini CV, Bernal P, Godoy P, Ramos JL, Segura A (2009) Cyclopropane fatty acids are involved in organic solvent tolerance but not in acid stress resistance in Pseudomonas putida DOT-T1E. Microb Biotechnol 2:253–261

  • Pittman MS, Robinson HC, Poole RK (2005) A bacterial glutathione transporter (Escherichia coli CydDC) exports reductant to the periplasm. J Biol Chem 280:32254–32261

  • Poblete-Castro I, Becker J, Dohnt K, dos Santos VM, Wittmann C (2012) Industrial biotechnology of Pseudomonas putida and related species. Appl Microbiol Biot 93:2279–2290

    Article  CAS  Google Scholar 

  • Qin T, Hu X, Hu J, Wang X (2014) Metabolic engineering of Corynebacterium glutamicum strain ATCC13032 to produce l-methionine. Biotechnol Appl Biochem 00:1–11

    Google Scholar 

  • Radmacher E, Stansen KC, Besra GS, Alderwick LJ, Maughan WN, Hollweg G, Sahm H, Wendisch VF, Eggeling L (2005) Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L-glutamate efflux of Corynebacterium glutamicum. Microbiology 151:1359–1368

    Article  CAS  PubMed  Google Scholar 

  • Ramos JL, Duque E, Godoy P, Segura A (1998) Efflux pumps involved in toluene tolerance in Pseudomonas putida DOT-T1E. J Bacteriol 180:3323–3329

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ramos JL, Duque E, Gallegos MT, Godoy P, Ramos-Gonzalez MI, Rojas A, Teran W, Segura A (2002) Mechanisms of solvent tolerance in gram-negative bacteria. Ann Rev Microbiol 56:743–768

    Article  CAS  Google Scholar 

  • Ramos JL, Krell T, Daniels C, Segura A, Duque E (2009) Responses of Pseudomonas to small toxic molecules by a mosaic of domains. Curr Opin Microbiol 12:215–220

    Article  CAS  PubMed  Google Scholar 

  • Ramos JL, Sol Cuenca M, Molina-Santiago C, Segura A, Duque E, Gomez-Garcia MR, Udaondo Z, Roca A (2015) Mechanisms of solvent resistance mediated by interplay of cellular factors in Pseudomonas putida. FEMS Microbiol Rev 39(4):555–566

    Article  PubMed  Google Scholar 

  • Rojas A, Duque E, Mosqueda G, Golden G, Hurtado A, Ramos JL, Segura A (2001) Three efflux pumps are required to provide efficient tolerance to toluene in Pseudomonas putida DOT-T1E. J Bacteriol 183:3967–3973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roma-Rodrigues C, Santos PM, Benndorf D, Rapp E, Sa-Correia I (2010) Response of Pseudomonas putida KT2440 to phenol at the level of membrane proteome. J Proteomics 73:1461–1478

    Article  CAS  PubMed  Google Scholar 

  • Saier MH Jr, Reddy VS, Tamang DG, Vastermark A (2014) The transporter classification database. Nucleic Acids Res 42:D251–D258

    Article  CAS  PubMed  Google Scholar 

  • Samin G, Pavlova M, Arif MI, Postema CP, Damborsky J, Janssen DB (2014) A Pseudomonas putida strain genetically engineered for 1,2,3-trichloropropane bioremediation. Appl Environ Microb 80:5467–5476

    Article  CAS  Google Scholar 

  • Sariaslani FS, Van Dyk TK, Huang L, Gatenby A, Ben-Bassat A (2005) Renewable resources for production of aromatic chemicals. Handbook of Industrial Biocatalysis 28:1–14

    Google Scholar 

  • Segura A, Godoy P, van Dillewijn P, Hurtado A, Arroyo N, Santacruz S, Ramos JL (2005) Proteomic analysis reveals the participation of energy- and stress-related proteins in the response of Pseudomonas putida DOT-T1E to toluene. J Bacteriol 187:5937–5945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah AA, Wang C, Chung YR, Kim JY, Choi ES, Kim SW (2013) Enhancement of geraniol resistance of Escherichia coli by MarA overexpression. J Biosci Bioeng 115:253–258

    Article  CAS  PubMed  Google Scholar 

  • Sikkema J, de Bont JA, Poolman B (1995) Mechanisms of membrane toxicity of hydrocarbons. Microbiol Rev 59:201–222

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stahmann KP, Revuelta JL, Seulberger H (2000) Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production. Appl Microbiol Biot 53:509–516

    Article  CAS  Google Scholar 

  • Stahmann KP, Arst HN Jr, Althofer H, Revuelta JL, Monschau N, Schlupen C, Gatgens C, Wiesenburg A, Schlosser T (2001) Riboflavin, overproduced during sporulation of Ashbya gossypii, protects its hyaline spores against ultraviolet light. Environ Microbiol 3:545–550

    Article  CAS  PubMed  Google Scholar 

  • Takagi H, Awano N, Kobayashi S, Noji M, Saito K, Nakamori S (1999) Overproduction of L-cysteine and L-cystine by expression of genes for feedback inhibition-insensitive serine acetyltransferase from Arabidopsis thaliana in Escherichia coli. FEMS Microbiol Lett 179:453–459

    CAS  PubMed  Google Scholar 

  • Takahashi C, Shirakawa J, Tsuchidate T, Okai N, Hatada K, Nakayama H, Tateno T, Ogino C, Kondo A (2012) Robust production of gamma-amino butyric acid using recombinant Corynebacterium glutamicum expressing glutamate decarboxylase from Escherichia coli. Enzyme Microb Technol 51:171–176

    Article  CAS  PubMed  Google Scholar 

  • Tashiro Y, Nomura N, Nakao R, Senpuku H, Kariyama R, Kumon H, Kosono S, Watanabe H, Nakajima T, Uchiyama H (2008) Opr86 is essential for viability and is a potential candidate for a protective antigen against biofilm formation by Pseudomonas aeruginosa. J Bacteriol 190:3969–3978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trotschel C, Deutenberg D, Bathe B, Burkovski A, Kramer R (2005) Characterization of methionine export in Corynebacterium glutamicum. J Bacteriol 187:3786–3794

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Van Dyk TK, Templeton LJ, Cantera KA, Sharpe PL, Sariaslani FS (2004) Characterization of the Escherichia coli AaeAB efflux pump: a metabolic relief valve? J Bacteriol 186:7196–7204

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Verhoef S, Ruijssenaars HJ, de Bont JA, Wery J (2007) Bioproduction of p-hydroxybenzoate from renewable feedstock by solvent-tolerant Pseudomonas putida S12. J Biotechnol 132:49–56

    Article  CAS  PubMed  Google Scholar 

  • Verhoef S, Wierckx N, Westerhof RG, de Winde JH, Ruijssenaars HJ (2009) Bioproduction of p-hydroxystyrene from glucose by the solvent-tolerant bacterium Pseudomonas putida S12 in a two-phase water-decanol fermentation. Appl Environ Microb 75:931–936

    Article  CAS  Google Scholar 

  • Verhoef S, Ballerstedt H, Volkers RJ, de Winde JH, Ruijssenaars HJ (2010) Comparative transcriptomics and proteomics of p-hydroxybenzoate producing Pseudomonas putida S12: novel responses and implications for strain improvement. Appl Microbiol Biot 87:679–690

    Article  CAS  Google Scholar 

  • Vermue M, Sikkema J, Verheul A, Bakker R, Tramper J (1993) Toxicity of homologous series of organic-solvents for the gram-positive bacteria Arthrobacter and Nocardia Sp and the gram-negative bacteria Acinetobacter and Pseudomonas Sp. Biotechnol Bioeng 42:747–758

    Article  CAS  PubMed  Google Scholar 

  • Volmer J, Neumann C, Buhler B, Schmid A (2014) Engineering of Pseudomonas taiwanensis VLB120 for constitutive solvent tolerance and increased specific styrene epoxidation activity. Appl Environ Microb 80:6539–6548

    Article  CAS  Google Scholar 

  • Vrljic M, Sahm H, Eggeling L (1996) A new type of transporter with a new type of cellular function: L-lysine export from Corynebacterium glutamicum. Mol Microbiol 22:815–826

    Article  CAS  PubMed  Google Scholar 

  • Wada M, Takagi H (2006) Metabolic pathways and biotechnological production of L-cysteine. Appl Microbiol Biot 73:48–54

    Article  CAS  Google Scholar 

  • Wang J-F, Xiong Z-Q, Li S-Y, Wang Y (2013a) Enhancing isoprenoid production through systematically assembling and modulating efflux pumps in Escherichia coli. Appl Microbiol Biot 97:8057–8067

    Article  CAS  Google Scholar 

  • Wang J, Cheng LK, Liu Q, Shen T, Chen N (2013b) Genetic engineering of Escherichia coli to enhance production of L-tryptophan. Appl Microbiol Biot 97:7587–7596

    Article  CAS  Google Scholar 

  • Watanabe R, Doukyu N (2012) Contributions of mutations in acrR and marR genes to organic solvent tolerance in Escherichia coli. AMB Express 2:58

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wenda S, Illner S, Mell A, Kragl U (2011) Industrial biotechnology—the future of green chemistry? Green Chem 13:3007–3047

    Article  CAS  Google Scholar 

  • Wierckx NJ, Ballerstedt H, de Bont JA, Wery J (2005) Engineering of solvent-tolerant Pseudomonas putida S12 for bioproduction of phenol from glucose. Appl Environ Microb 71:8221–8227

    Article  CAS  Google Scholar 

  • Wiriyathanawudhiwong N, Ohtsu I, Li ZD, Mori H, Takagi H (2009) The outer membrane TolC is involved in cysteine tolerance and overproduction in Escherichia coli. Appl Microbiol Biot 81:903–913

    Article  CAS  Google Scholar 

  • Yakimov MM, Golyshin PN, Lang S, Moore ER, Abraham WR, Lunsdorf H, Timmis KN (1998) Alcanivorax borkumensis gen. nov., sp. nov., a new, hydrocarbon-degrading and surfactant-producing marine bacterium. Int J Syst Bacteriol 48 Pt 2:339–348

    Article  CAS  PubMed  Google Scholar 

  • Yamada S, Awano N, Inubushi K, Maeda E, Nakamori S, Nishino K, Yamaguchi A, Takagi H (2006) Effect of drug transporter genes on cysteine export and overproduction in Escherichia coli. Appl Environ Microb 72:4735–4742

    Article  CAS  Google Scholar 

  • Yin L, Shi F, Hu X, Chen C, Wang X (2013) Increasing l-isoleucine production in Corynebacterium glutamicum by overexpressing global regulator Lrp and two-component export system BrnFE. J Appl Microbiol 114:1369–1377

    Article  CAS  PubMed  Google Scholar 

  • Youngquist JT, Lennen RM, Ranatunga DR, Bothfeld WH, Marner WD 2nd, Pfleger BF (2012) Kinetic modeling of free fatty acid production in Escherichia coli based on continuous cultivation of a plasmid free strain. Biotechnol Bioeng 109:1518–1527

    Article  CAS  PubMed  Google Scholar 

  • Zakataeva NP, Aleshin VV, Tokmakova IL, Troshin PV, Livshits VA (1999) The novel transmembrane Escherichia coli proteins involved in the amino acid efflux. FEBS Lett 452:228–232

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Jeffrey C. Cameron for reading the manuscript.

Compliance with ethical standards

This work was supported by grants from the National Science Foundation (EFRI-1240268, CBET-1149678). NLH is the recipient of a NIH Chemistry-Biology Interface Training Program fellowship (T32 GM008505) and a Graduate Engineering Research Scholars fellowship from the UW-Madison College of Engineering. This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Chemical and Biological Engineering, University of Wisconsin—Madison, Madison, WI, 53706, USA

    Christopher M. Jones, Néstor J. Hernández Lozada & Brian F. Pfleger

  2. Microbiology Doctoral Training Program, University of Wisconsin—Madison, Madison, WI, 53706, USA

    Brian F. Pfleger

  3. 3629 Engineering Hall, 1415 Engineering Drive, Madison, WI, 53706, USA

    Brian F. Pfleger

Authors
  1. Christopher M. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Néstor J. Hernández Lozada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian F. Pfleger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brian F. Pfleger.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jones, C.M., Hernández Lozada, N.J. & Pfleger, B.F. Efflux systems in bacteria and their metabolic engineering applications. Appl Microbiol Biotechnol 99, 9381–9393 (2015). https://doi.org/10.1007/s00253-015-6963-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-015-6963-9

Keywords

Search

Navigation