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In situ product removal in fermentation systems: improved process performance and rational extractant selection

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Abstract

The separation of inhibitory compounds as they are produced in biotransformation and fermentation systems is termed in situ product removal (ISPR). This review examines recent ISPR strategies employing several classes of extractants including liquids, solids, gases, and combined extraction systems. Improvement through the simple application of an auxiliary phase are tabulated and summarized to indicate the breadth of recent ISPR activities. Studies within the past 5 years that have highlighted and have discussed “second phase” properties, and that have an effect on fermentation performance, are particular focus of this review. ISPR, as a demonstrably effective processing strategy, continues to be widely adopted as more applications are explored; however, focus on the properties of extractants and their rational selection based on first principle considerations will likely be key to successfully applying ISPR to more challenging target molecules.

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References

  • Anvari M, Khayati G (2009) In situ recovery of 2, 3-butanediol from fermentation by liquid–liquid extraction. J Ind Microbiol Biotechnol 36:313–317

    Article  PubMed  CAS  Google Scholar 

  • Barton WE, Daugulis AJ (1992) Evaluation of solvents for extractive butanol fermentation with Clostridium acetobutylicum and the use of poly (propylene glycol) 1200. Appl Microbiol Biotechnol 36:632–639

    Article  CAS  Google Scholar 

  • Boghigian BA, Myint M, Wu J, Pfeifer BA (2011) Simultaneous production and partitioning of heterologous polyketide and isoprenoid natural products in an Escherichia coli two-phase bioprocess. J Ind Microbiol Biotechnol 38:1809–1820

    Article  PubMed  CAS  Google Scholar 

  • Boontawan P, Kanchanathawee S, Boontawan A (2011) Extractive fermentation of l-(+)-lactic acid by Pediococcus pentosaceus using electrodeionization (EDI) technique. Biochem Eng J 54:192–199

    Article  CAS  Google Scholar 

  • Brennan TC, Turner CD, Krömer JO, Nielsen LK (2012) Alleviating monoterpene toxicity using a two-phase extractive fermentation for the bioproduction of jet fuel mixtures in Saccharomyces cerevisiae. Biotechnol Bioeng 109:2513–2522

    Article  PubMed  CAS  Google Scholar 

  • Chavez-Santoscoy A, Benavides J, Vermaas W, Rito-Palomares M (2010) Application of aqueous two-phase systems for the potential extractive fermentation of cyanobacterial products. Chem Eng Technol 33:177–182

    Article  CAS  Google Scholar 

  • Choi JM, Yeom SH (2011) Simulation study of biobutanol production in a polymer-loaded two-phase partitioning bioreactor (PL-TPPB): model development. Korean J Chem Eng 28:2170–2177

    Article  CAS  Google Scholar 

  • Craig T, Daugulis AJ (2012) Polymer characterization and optimization of conditions for the enhanced bioproduction of benzaldehyde by Pichia pastoris in a two-; phase partitioning bioreactor. Biotechnol Bioeng 110:1098–1105

    Article  PubMed  CAS  Google Scholar 

  • Dafoe JTS, Daugulis AJ (2011) Bioproduction of cis-(1S, 2R)-indandiol, a chiral pharmaceutical intermediate, using a solid–liquid two-phase partitioning bioreactor for enhanced removal of inhibitors. J Chem Technol Biotechnol 86:1379–1385

    Article  CAS  Google Scholar 

  • Dafoe JT, Daugulis AJ (2013a) Production of 4-valerolactone by an equilibrium-limited transformation in a partitioning bioreactor: impact of absorptive polymer properties. Bioprocess Biosyst Eng. doi:10.1007/s00449-013-1020-5

    PubMed  Google Scholar 

  • Dafoe JT, Daugulis AJ (2013b) Manipulating the composition of absorbent polymers affects product and by-product concentration profiles in the biphasic biotransformation of indene to cis-1, 2-indandiol. Biochem Eng J 77:7–14

    Article  CAS  Google Scholar 

  • Dhamole PB, Wang Z, Liu Y, Wang B, Feng H (2012) Extractive fermentation with non-ionic surfactants to enhance butanol production. Biomass Bioenergy 40:112–119

    Article  CAS  Google Scholar 

  • Fam H, Daugulis AJ (2012) Substrate mass transport in two-phase partitioning bioreactors employing liquid and solid non-aqueous phases. Bioprocess Biosyst Eng 35:1367–1374

    Article  PubMed  CAS  Google Scholar 

  • Galaction A, Poştaru M, Caşcaval D, Kloetzer L (2013) Selective separation of carboxylic acids obtained by succinic acid fermentation using facilitated pertraction. Solvent Extr Ion Exch 31:171–183

    Article  CAS  Google Scholar 

  • Gao F, Daugulis AJ (2009) Bioproduction of the aroma compound 2-phenylethanol in a solid–liquid two-phase partitioning bioreactor system by Kluyveromyces marxianus. Biotechnol Bioeng 104:332–339

    Article  PubMed  CAS  Google Scholar 

  • Gao MT, Shimamura T, Ishida N, Takahashi H (2011) pH-uncontrolled lactic acid fermentation with activated carbon as an adsorbent. Enzyme Microb Technol 48:526–530

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Chavez LY, Garsia CM, Schuur B, de Haan AB (2013) Bio-butanol recovery using non-fluorinated task specific ionic liquids (TSILs). Ind Eng Chem Res 52:4902–4910

    Article  CAS  Google Scholar 

  • Garikipati SJ, McIver AM, Peeples TL (2009) Whole-cell biocatalysis for 1-naphthol production in liquid–liquid biphasic systems. Appl Environ Microbiol 75:6545–6552

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Grady MC, Jahic M, Patnaik R (2010) Method for producing butanol using two-phase extractive fermentation. Patent application US 20100221802 A1

  • Hu Q, Xu Y, Nie Y (2010) Enhancement of Candida parapsilosis catalyzing deracemization of (R, S)-1-phenyl-1, 2-ethanediol to its (S)-enantiomer by a highly productive “two-in-one” resin-based in situ product removal strategy. Bioresour Technol 101:8461–8463

    Article  PubMed  CAS  Google Scholar 

  • Hu Z, Zhang X, Wu Z, Qi H, Wang Z (2012) Perstraction of intracellular pigments by submerged cultivation of Monascus in nonionic surfactant micelle aqueous solution. Appl Microbiol Biotechnol 94:81–89

    Article  PubMed  CAS  Google Scholar 

  • Hua D, Lin S, Li Y, Chen H, Zhang Z, Du Y, Zhang X, Xu P (2010) Enhanced 2-phenylethanol production from l-phenylalanine via in situ product adsorption. Biocatal Biotransfor 28:259–266

    Article  CAS  Google Scholar 

  • Jain AN, Khan TR, Daugulis AJ (2010) Bioproduction of benzaldehyde in a solid–liquid two-phase partitioning bioreactor using Pichia pastoris. Biotechnol Lett 32:1649–1654

    Article  PubMed  CAS  Google Scholar 

  • Jeon BS, Moon C, Kim B, Kim H, Um Y, Sang B (2013) In situ extractive fermentation for the production of hexanoic acid from galactitol by Clostridium sp. BS-1. Enzyme Microb Technol 53:143–151

    Article  PubMed  CAS  Google Scholar 

  • Jeong G, Kim S, Park D (2013) Detoxification of hydrolysate by reactive-extraction for generating biofuels. Biotechnol Bioprocess Eng 18:88–93

    Article  CAS  Google Scholar 

  • Jin H, Liu Z, Hu Z, Zheng Y (2013) Production of (R)-epichlorohydrin from 1, 3-dichloro-2-propanol by two-step biocatalysis using haloalcohol dehalogenase and epoxide hydrolase in two-phase system. Biochem Eng J 74:1–7

    Article  CAS  Google Scholar 

  • Julsing MK, Kuhn D, Schmid A, Bühler B (2012) Resting cells of recombinant E. coli show high epoxidation yields on energy source and high sensitivity to product inhibition. Biotechnol Bioeng 109:1109–1119

    Article  PubMed  CAS  Google Scholar 

  • Jung D, Choi W, Choi K, Jung E, Yun H, Kazlauskas RJ, Kim B (2013) Bioconversion of p-coumaric acid to p-hydroxystyrene using phenolic acid decarboxylase from B. amyloliquefaciens in biphasic reaction system. Appl Microbiol Biotechnol 97:1501–1511

    Article  PubMed  CAS  Google Scholar 

  • Keasler SJ, Lewin JL, Schultz NE, Ross RB, Gryska NM, Nakamura M, Siepmann JI (2013) Molecular insights for the optimization of solvent-based selective extraction of ethanol from fermentation broths. AIChE J 59:3065–3070

    Article  CAS  Google Scholar 

  • Khan TR, Daugulis AJ (2010) Application of solid–liquid TPPBs to the production of l-phenylacetylcarbinol from benzaldehyde using Candida utilis. Biotechnol Bioeng 107:633–641

    Article  PubMed  CAS  Google Scholar 

  • Krug TA, Daugulis AJ (1983) Ethanol production using Zymomonas mobilis immobilized on an ion exchange resin. Biotechnol Lett 5:159–164

    Article  CAS  Google Scholar 

  • Kuhn D, Julsing MK, Heinzle E, Bühler B (2012) Systematic optimization of a biocatalytic two-liquid phase oxyfunctionalization process guided by ecological and economic assessment. Green Chem 14:645–653

    Article  CAS  Google Scholar 

  • Leeman M, Vossebeld F, Visser TJ, Schuur B, de Haan AB (2013) Novel extractants for the recovery of fermentation derived lactic acid. Sep Purif Technol 111:82–89

    Article  CAS  Google Scholar 

  • Li Q, Cai H, Hao B, Zhang C, Yu Z, Zhou S, Chenjuan L (2010) Enhancing clostridial acetone–butanol–ethanol (ABE) production and improving fuel properties of ABE-enriched biodiesel by extractive fermentation with biodiesel. Appl Biochem Biotechnol 162:2381–2386

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Wang D, Hu G, Xing J, Su Z (2011a) Integrated bioprocess for high-efficiency production of succinic acid in an expanded-bed adsorption system. Biochem Eng J 56:150–157

    Article  CAS  Google Scholar 

  • Li SY, Srivastava R, Parnas RS (2011b) Study of in situ 1-butanol pervaporation from A–B–E fermentation using a PDMS composite membrane: validity of solution-diffusion model for pervaporative A–B–E fermentation. Biotechnol Prog 27:111–120

    Article  PubMed  CAS  Google Scholar 

  • Liu S, Wu Q, Zhang J, Mo S (2011) Production of epsilon-poly-l-lysine by Streptomyces sp. using resin-based, in situ product removal. Biotechnol Lett 33:1581–1585

    Article  PubMed  CAS  Google Scholar 

  • Mao S, Hua B, Wang N, HU X, Ge Z, Li Y, Liu S, Lu F (2012) 11α hydroxylation of 16α, 17-epoxypro-gesterone in biphasic ionic liquid/water system by Aspergillus ochraceus. J Chem Technol Biotechnol 88:287–292

    Article  CAS  Google Scholar 

  • Mei J, Min H, Lü Z (2009) Enhanced biotransformation of l-phenylalanine to 2-phenylethanol using an in situ product adsorption technique. Proc Biochem 44:886–890

    Article  CAS  Google Scholar 

  • Mihal M, Markoš J, Annus J, Štefuca V (2012) Intensification of 1-phenylethanol production by periodical membrane extraction of the product from fermentation broth. J Chem Technol Biot 87:1017–1026

    Article  CAS  Google Scholar 

  • Mirata MA, Heerd D, Schrader J (2009) Integrated bioprocess for the oxidation of limonene to perillic acid with Pseudomonas putida DSM 12264. Proc Biochem 44:764–771

    Article  CAS  Google Scholar 

  • Muñoz R, Daugulis AJ, Hernández M, Quijano G (2012) Recent advances in two-phase partitioning bioreactors for the treatment of volatile organic compounds. Biotechnol Adv 30:1707–1720

    Article  PubMed  CAS  Google Scholar 

  • Neves CMSS, Granjo JFO, Freire MG, Robertson A, Oliveira NMC, Coutinho JAP (2011) Separation of ethanol–water mixtures by liquid–liquid extraction using phosphonium-based ionic liquids. Green Chem 13:1517–1526

    Article  CAS  Google Scholar 

  • Nielsen DR, Amarasiriwardena GS, Prather KLJ (2010) Predicting the adsorption of second-generation biofuels by polymeric resins with applications for in situ product recovery (ISPR). Bioresour Technol 101:2762–2769

    Article  PubMed  CAS  Google Scholar 

  • Oudshoorn A, van der Wielen LAM, Straathof AJJ (2009) Assessment of options for selective 1-butanol recovery from aqueous solution. Ind Eng Chem Res 48:7325–7336

    Article  CAS  Google Scholar 

  • Pahlavanzadeh H, Khayati G, Vasheghani-Farahani E, Ghaemi N (2009) Extractive capacity of oleyl alcohol on 2, 3-butanediol production in fermentation process with use of Klebsiella pneumoniae PTCC 1290. Iran J Chem Chem Eng -Int Engl Ed 28:103–109

    CAS  Google Scholar 

  • Parent JS, Capela M, Dafoe JT, Daugulis AJ (2012) A first principles approach to identifying polymers for use in two-phase partitioning bioreactors. J Chem Technol Biotechnol 87:1059–1065

    Article  CAS  Google Scholar 

  • Poleo EE, Daugulis AJ (2013) A comparison of three first principles methods for predicting solute–polymer affinity, and the simultaneous biodegradation of phenol and butyl acetate in a two-phase partitioning bioreactor. J Chem Technol Biotechnol. doi:10.1002/jctb.4116

    Google Scholar 

  • Quijano G, Hernandez M, Villaverde S, Thalasso F, Muñoz R (2010) A step-forward in the characterization and potential applications of solid and liquid oxygen transfer vectors. Appl Microbiol Biotechnol 85:543–551

    Article  PubMed  CAS  Google Scholar 

  • Ranjan R, Thust S, Gounaris CE, Woo M, Floudas CA, Keitz MV, Valentas KJ, Wei J, Tsapatsis M (2009) Adsorption of fermentation inhibitors from lignocellulosic biomass hydrolyzates for improved ethanol yield and value-added product recovery. Microporous Mesoporous Mater 122:143–148

    Article  CAS  Google Scholar 

  • Redwood MD, Orozco RL, Majewski AJ, Macaskie LE (2012) Electro-extractive fermentation for efficient biohydrogen production. Bioresour Technol 107:166–174

    Article  PubMed  CAS  Google Scholar 

  • Rehmann L, Daugulis AJ (2007) Biodegradation of biphenyl in a solid-liquid two-phase partitioning bioreactor. Biochem Eng J 36:195–201

    Article  CAS  Google Scholar 

  • Rong S, Ding B, Zhang X, Zheng X, Wang Y (2011) Enhanced biotransformation of 2-phenylethanol with ethanol oxidation in a solid–liquid two-phase system by active dry yeast. Curr Microbiol 63:503–509

    Article  PubMed  CAS  Google Scholar 

  • Ruetti DP, Lacroix C, Jeremic T, Mathis M, Die A, Vollenweider S (2011) Development of a reversible binding process for in situ removal of 3-hydroxypropionaldehyde during biotechnological conversion of glycerol. Biochem Eng J 55:176–184

    Article  CAS  Google Scholar 

  • Tanaka S, Tashiro Y, Kobayashi G, Ikegami T, Negishi H, Sakaki K (2012) Membrane-assisted extractive butanol fermentation by Clostridium saccharoperbutylacetonicum N1-4 with 1-dodecanol as the extractant. Bioresour Technol 116:448–452

    Article  PubMed  CAS  Google Scholar 

  • van den Berg C, Heeres AS, van der Wielen LA, Straathof AJ (2013) Simultaneous clostridial fermentation, lipase-catalyzed esterification, and ester extraction to enrich diesel with butyl butyrate. Biotechnol Bioeng 110:137–142

    Article  PubMed  CAS  Google Scholar 

  • Verhoef S, Wierckx N, Westerhof R, 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 Microbiol 75:931–936

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang Z, Liang R, Xu J, Liu Y, Qi H (2010) A closed concept of extractive whole cell Microbial transformation of benzaldehyde into l-phenylacetylcarbinol by Saccharomyces cerevisiae in novel polyethylene-glycol-induced cloud-point system. Appl Biochem Biotechnol 160:1865–1877

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Dong Q, Guan A, Meng C, Shi X, Guo Y (2011a) Synergistic inhibition effect of 2-phenylethanol and ethanol on bioproduction of natural 2-phenylethanol by Saccharomyces cerevisiae and process enhancement. J Biosci Bioeng 112:26–31

    Article  PubMed  CAS  Google Scholar 

  • Wang H, Dong Q, Meng C, Guo Y (2011b) A continuous and adsorptive bioprocess for efficient production of the natural aroma chemical 2-phenylethanol with yeast. Enzyme Microb Technol 48:404–407

    Article  PubMed  CAS  Google Scholar 

  • Wang P, Wang Y, Su Z (2012a) Microbial production of propionic acid with Propionibacterium freudenreichii using an anion exchanger-based in situ product recovery (ISPR) process with direct and indirect contact of cells. Appl Biochem Biotechnol 166:1–13

    Article  CAS  Google Scholar 

  • Wang P, Wang Y, Liu Y, Shi H, Su Z (2012b) Novel in situ product removal technique for simultaneous production of propionic acid and vitamin B12 by expanded bed adsorption bioreactor. Bioresour Technol 104:652–659

    Article  PubMed  CAS  Google Scholar 

  • Wei G, Yang X, Zhou W, Lin J, Wei D (2009) Adsorptive bioconversion of ethylene glycol to glycolic acid by Gluconobacter oxydans DSM 2003. Biochem Eng J 47:127–131

    Article  CAS  Google Scholar 

  • Xue Y, Liu Z, Xu M, Wang Y, Zheng Y, Shen Y (2010) Enhanced biotransformation of (R, S)-mandelonitrile to (R)-(−)-mandelic acid with in situ production removal by addition of resin. Biochem Eng J 53:143–149

    Article  CAS  Google Scholar 

  • Xue C, Zhao J, Lu C, Yang S, Bai F, Tang I (2012) High-titer n-butanol production by Clostridium acetobutylicum JB200 in fed-batch fermentation with intermittent gas stripping. Biotechnol Bioeng 109:2746–2756

    Article  PubMed  CAS  Google Scholar 

  • Zou S, Du E, Hu Z, Zheng Y (2013) Enhanced biotransformation of 1, 3-dichloro-2-propanol to epichlorohydrin via resin-based in situ product removal process. Biotechnol Lett 35:937–942

    Article  PubMed  CAS  Google Scholar 

  • Zúñiga C, Morales M, Le Borgne S, Revah S (2011) Production of poly-β-hydroxybutyrate (PHB) by Methylobacterium organophilum isolated from a methanotrophic consortium in a two-phase partition bioreactor. J Hazard Mater 190:876–882

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Chemical Engineering, Queen’s University, Kingston, ON, K7L 3N6, Canada

    Julian T. Dafoe & Andrew J. Daugulis

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  1. Julian T. Dafoe
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Dafoe, J.T., Daugulis, A.J. In situ product removal in fermentation systems: improved process performance and rational extractant selection. Biotechnol Lett 36, 443–460 (2014). https://doi.org/10.1007/s10529-013-1380-6

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