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Polyhydroxyalkanoic acids from structurally-unrelated carbon sources in Escherichia coli

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Abstract

Polyhydroxyalkanoates (PHAs) that contain varied monomers with different chain lengths/structures were normally synthesized when a structurally-related precursor was present. The biosynthesis of PHAs from unrelated carbon sources in microorganisms including Escherichia coli met many challenges in the past. Recently, with the development of metabolic engineering and synthetic biology, the production of PHAs from unrelated carbon sources obtained a breakthrough. Polyesters containing 2-hydroxypropionate, 3-hydroxypropionate, 4-hydroxybutyrate, 3-hydroxyvalarate, and medium-chain-length 3-hydroxyalkanoate monomers can all be synthesized in E. coli by integrating exogenous or endogenous pathways and/or genes. This review will summarize the progresses in this area. In addition, the strategies that lead to the production of PHAs with varied monomers and high polymer content in the cell are discussed.

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References

  • Agnew DE, Stevermer AK, Youngquist JT, Pfleger BF (2012) Engineering Escherichia coli for production of C(12)-C(14) polyhydroxyalkanoate from glucose. Metab Eng 14:705–713. doi:10.1016/j.ymben.2012.08.003

    Article  CAS  Google Scholar 

  • Aldor IS, Kim SW, Prather KL, Keasling JD (2002) Metabolic engineering of a novel propionate-independent pathway for the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in recombinant Salmonella enterica serovar typhimurium. Appl Environ Microbiol 68:3848–3854

    Article  CAS  Google Scholar 

  • Anderson AJ, Dawes EA (1990) Occurrence, metabolism, metabolic role, and industrial uses of bacterial polyhydroxyalkanoates. Microbiol Rev 54:450–472

    CAS  Google Scholar 

  • Andreeßen B, Lange AB, Robenek H, Steinbüchel A (2010) Conversion of glycerol to poly(3-hydroxypropionate) in recombinant Escherichia coli. Appl Environ Microbiol 76:622–626. doi:10.1128/AEM.02097-09

    Article  Google Scholar 

  • Byrom D (1987) Polymer synthesis by microorganisms: technology and economics. Trends Biotechnol 5:246–250

    Article  CAS  Google Scholar 

  • Chen GQ (2009) A microbial polyhydroxyalkanoates (PHA) based bio- and materials industry. Chem Soc Rev 38:2434–2446. doi:10.1039/b812677c

    Article  CAS  Google Scholar 

  • Chen Q, Wang Q, Wei G, Liang Q, Qi Q (2011) Production in Escherichia coli of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with differing monomer compositions from unrelated carbon sources. Appl Environ Microbiol 77:4886–4893. doi:10.1128/AEM.00091-11

    Article  CAS  Google Scholar 

  • Cho A, Yun H, Park JH, Lee SY, Park S (2010) Prediction of novel synthetic pathways for the production of desired chemicals. BMC Syst Biol 4:35. doi:10.1186/1752-0509-4-35

    Article  Google Scholar 

  • Choi MH, Yoon SC, Lenz RW (1999) Production of poly(3-hydroxybutyric acid-co-4-hydroxybutyric acid) and poly(4-hydroxybutyric acid) without subsequent degradation by Hydrogenophaga pseudoflava. Appl Environ Microbiol 65:1570–1577

    CAS  Google Scholar 

  • Dellomonaco C, Clomburg JM, Miller EN, Gonzalez R (2011) Engineered reversal of the beta-oxidation cycle for the synthesis of fuels and chemicals. Nature 476:355–359. doi:10.1038/nature10333

    Article  CAS  Google Scholar 

  • Doi Y, Kunioka M, Nakamura Y, Soga K (1988) Nuclear magnetic resonance studies on unusual bacterial copolyesters of 3-hydroxybutyrate and 4-hydroxybutyrate. Macromolecules 21:2722–2727

    Article  CAS  Google Scholar 

  • Eschenlauer AC, Stoup SK, Srienc F, Somers DA (1996) Production of heteropolymeric polyhydroxyalkanoate in Escherichia coli from a single carbon source. Int J Biol Macromol 19:121–130

    Article  CAS  Google Scholar 

  • Felnagle EA, Chaubey A, Noey EL, Houk KN, Liao JC (2012) Engineering synthetic recursive pathways to generate non-natural small molecules. Nat Chem Biol 8:518–526. doi:10.1038/nchembio.959

    Article  CAS  Google Scholar 

  • Fidler S, Dennis D (1992) Polyhydroxyalkanoate production in recombinant Escherichia coli. FEMS Microbiol Rev 9:231–235

    CAS  Google Scholar 

  • Fukui T, Abe H, Doi Y (2002) Engineering of Ralstonia eutropha for production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from fructose and solid-state properties of the copolymer. Biomacromolecules 3:618–624

    Article  CAS  Google Scholar 

  • Fukui T, Suzuki M, Tsuge T, Nakamura S (2009) Microbial synthesis of poly((R)-3-hydroxybutyrate-co-3-hydroxypropionate) from unrelated carbon sources by engineered Cupriavidus necator. Biomacromolecules 10:700–706. doi:10.1021/bm801391j

    Article  CAS  Google Scholar 

  • Green PR, Kemper J, Schechtman L, Guo L, Satkowski M, Fiedler S, Steinbuchel A, Rehm BH (2002) Formation of short-chain length/medium chain length polyhydroxyalkanoate copolymers by fatty acid beta-oxidation inhibited Ralstonia eutropha. Biomacromolecules 3:208–213

    Article  CAS  Google Scholar 

  • Hazer B, Steinbüchel A (2007) Increased diversification of polyhydroxyalkanoates by modification reactions for industrial and medical applications. Appl Microbiol Biotechnol 74:1–12. doi:10.1007/s00253-006-0732-8

    Article  CAS  Google Scholar 

  • Hein S, Söhling B, Gottschalk G, Steinbüchel A (1997) Biosynthesis of poly(4-hydroxybutyric acid) by recombinant strains of Escherichia coli. FEMS Microbiol Lett 153:411–418

    Article  CAS  Google Scholar 

  • Jiang X, Meng X, Xian M (2009) Biosynthetic pathways for 3-hydroxypropionic acid production. Appl Microbiol Biotechnol 82:995–1003. doi:10.1007/s00253-009-1898-7

    Article  CAS  Google Scholar 

  • 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 105:161–171. doi:10.1002/bit.22548

    Article  CAS  Google Scholar 

  • Kang CK, Kusaka S, Doi Y (1995) Structure and properties of poly (3-hydroxybutyrate-co-4-hydroxybutyrate) produced by Alcaligenes latus. Biotechnol Lett 17:583–588

    Article  CAS  Google Scholar 

  • Klinke S, Ren Q, Witholt B, Kessler B (1999) Production of medium-chain-length poly(3-hydroxyalkanoates) from gluconate by recombinant Escherichia coli. Appl Environ Microbiol 65:540–548

    CAS  Google Scholar 

  • Langenbach S, Rehm BH, Steinbüchel A (1997) Functional expression of the PHA synthase gene phaC1 from Pseudomonas aeruginosa in Escherichia coli results in poly(3-hydroxyalkanoate) synthesis. FEMS Microbiol Lett 150:303–309

    Article  CAS  Google Scholar 

  • Law KH, Chan PL, Lau WS, Cheng YC, Leung YC, Lo WH, Lawford H, Yu HF (2004) Construction of recombinant Escherichia coli strains for production of poly-(3-hydroxybutyrate-co-3-hydroxyvalerate). Appl Biochem Biotechnol 113–116:361–372

    Article  Google Scholar 

  • Lee JW, Na D, Park JM, Lee J, Choi S, Lee SY (2012) Systems metabolic engineering of microorganisms for natural and non-natural chemicals. Nat Chem Biol 8:536–546. doi:10.1038/nchembio.970

    Google Scholar 

  • Li R, Chen Q, Wang PG, Qi Q (2007a) A novel-designed Escherichia coli for the production of various polyhydroxyalkanoates from inexpensive substrate mixture. Appl Microbiol Biotechnol 75:1103–1109

    Article  CAS  Google Scholar 

  • Li R, Zhang H, Qi Q (2007b) The production of polyhydroxyalkanoates in recombinant Escherichia coli. Bioresour Technol 98:2313–2320. doi:10.1016/j.biortech.2006.09.014

    Article  CAS  Google Scholar 

  • Li ZJ, Shi ZY, Jian J, Guo YY, Wu Q, Chen GQ (2010) Production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) from unrelated carbon sources by metabolically engineered Escherichia coli. Metab Eng 12:352–359. doi:10.1016/j.ymben.2010.03.003

    Article  CAS  Google Scholar 

  • Meng DC, Shi ZY, Wu LP, Zhou Q, Wu Q, Chen JC, Chen GQ (2012) Production and characterization of poly (3-hydroxypropionate-co-4-hydroxybutyrate) with fully controllable structures by recombinant Escherichia coli containing an engineered pathway. Metab Eng 14:317–324

    Article  CAS  Google Scholar 

  • Nakamura S, Kunioka M, Doi Y (1991) Biosynthesis and characterization of bacterial poly (3-hydroxybutyrate-co-3-hydroxypropionate). Macromol Rep 28:15–24

    Google Scholar 

  • Nomura CT, Taguchi K, Gan Z, Kuwabara K, Tanaka T, Takase K, Doi Y (2005) Expression of 3-ketoacyl-acyl carrier protein reductase (fabG) genes enhances production of polyhydroxyalkanoate copolymer from glucose in recombinant Escherichia coli JM109. Appl Environ Microbiol 71:4297–4306. doi:10.1128/AEM.71.8.4297-4306.2005

    Article  CAS  Google Scholar 

  • Nomura CT, Taguchi K, Taguchi S, Doi Y (2004) Coexpression of genetically-engineered 3-ketoacyl-ACP synthase III (fabH) and polyhydroxyalkanoate synthase (phaC) genes leads to short-chain-length-medium-chain-length polyhydroxyalkanoate copolymer production from glucose in Escherichia coli JM109. Appl Environ Microbiol 70:999–1007

    Article  CAS  Google Scholar 

  • Park SJ, Choi J, Lee SY (2005) Engineering of Escherichia coli fatty acid metabolism for the production of polyhydroxyalkanoates. Enzym Microb Technol 36:579–588

    Article  CAS  Google Scholar 

  • Park SJ, Lee TW, Lim SC, Kim TW, Lee H, Kim MK, Lee SH, Song BK, Lee SY (2012) Biosynthesis of polyhydroxyalkanoates containing 2-hydroxybutyrate from unrelated carbon source by metabolically engineered Escherichia coli. Appl Microbiol Biotechnol 93:273–283. doi:10.1007/s00253-011-3530-x

    Article  Google Scholar 

  • Park SJ, Yang TH, Kang HO, Lee SH, Lee EJ, Kim TW, Lee SY (2008) Mutants of PHA synthase from Pseudomonas sp. 6-19 and method for preparing lactate homopolymer or copolymer using the same. WO Patent 2,008,062,999

  • Qi Q, Rehm BH, Steinbüchel A (1997) Synthesis of poly(3-hydroxyalkanoates) in Escherichia coli expressing the PHA synthase gene phaC2 from Pseudomonas aeruginosa: comparison of PhaC1 and PhaC2. FEMS Microbiol Lett 157:155–162

    Article  CAS  Google Scholar 

  • Qiu YZ, Han J, Guo JJ, Chen GQ (2005) Production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from gluconate and glucose by recombinant Aeromonas hydrophila and Pseudomonas putida. Biotechnol Lett 27:1381–1386. doi:10.1007/s10529-005-3685-6

    Article  CAS  Google Scholar 

  • Rathnasingh C, Raj SM, Jo JE, Park S (2009) Development and evaluation of efficient recombinant Escherichia coli strains for the production of 3-hydroxypropionic acid from glycerol. Biotechnol Bioeng 104:729–739. doi:10.1002/bit.22429

    CAS  Google Scholar 

  • Rathnasingh C, Raj SM, Lee Y, Catherine C, Ashok S, Park S (2012) Production of 3-hydroxypropionic acid via malonyl-CoA pathway using recombinant Escherichia coli strains. J Biotechnol 157:633–640. doi:10.1016/j.jbiotec.2011.06.008

    Article  CAS  Google Scholar 

  • Rehm BH, Mitsky TA, Steinbüchel A (2001) Role of fatty acid de novo biosynthesis in polyhydroxyalkanoic acid (PHA) and rhamnolipid synthesis by pseudomonads: establishment of the transacylase (PhaG)-mediated pathway for PHA biosynthesis in Escherichia coli. Appl Environ Microbiol 67:3102–3109. doi:10.1128/AEM.67.7.3102-3109.2001

    Article  CAS  Google Scholar 

  • Rehm BH, Steinbüchel A (2001) Heterologous expression of the acyl-acyl carrier protein thioesterase gene from the plant Umbellularia californica mediates polyhydroxyalkanoate biosynthesis in recombinant Escherichia coli. Appl Microbiol Biotechnol 55:205–209

    Article  CAS  Google Scholar 

  • Renner G, Pongratz K, Braunegg G (1996) Production of poly (3-hydroxybutyrate-co-4-hydroxybutyrate) by Comamonas testosteronii A3. Food Technol Biotech 34:2–3

    Google Scholar 

  • Södergård A, Stolt M (2002) Properties of lactic acid based polymers and their correlation with composition. Prog Polym Sci 27:1123–1163

    Article  Google Scholar 

  • Schubert P, Steinbüchel A, Schlegel HG (1988) Cloning of the Alcaligenes eutrophus genes for synthesis of poly-beta-hydroxybutyric acid (PHB) and synthesis of PHB in Escherichia coli. J Bacteriol 170:5837–5847

    CAS  Google Scholar 

  • Slater SC, Voige WH, Dennis DE (1988) Cloning and expression in Escherichia coli of the Alcaligenes eutrophus H16 poly-beta-hydroxybutyrate biosynthetic pathway. J Bacteriol 170:4431–4436

    CAS  Google Scholar 

  • Söhling B, Gottschalk G (1996) Molecular analysis of the anaerobic succinate degradation pathway in Clostridium kluyveri. J Bacteriol 178:871–880

    Google Scholar 

  • Song S, Hein S, Steinbüchel A (1999) Production of poly (4-hydroxybutyric acid) by fed-batch cultures of recombinant strains of Escherichia coli. Biotechnol Lett 21:193–197

    Article  CAS  Google Scholar 

  • Song SS, Ma H, Gao ZX, Jia ZH, Zhang X (2005) Construction of recombinant Escherichia coli strains producing poly (4-hydroxybutyric acid) homopolyester from glucose. Wei Sheng Wu Xue Bao 45:382–386

    CAS  Google Scholar 

  • Steinbüchel A, Lütke-Eversloh T (2003) Metabolic engineering and pathway construction for biotechnological production of relevant polyhydroxyalkanoates in microorganisms. Biochem Eng J 16:81–96

    Article  Google Scholar 

  • Steinbüchel A, Pieper U (1992) Production of a copolyester of 3-hydroxybutyric acid and 3-hydroxyvaleric acid from single unrelated carbon sources by a mutant of Alcaligenes eutrophus. Appl Microbiol Biotechnol 37:1–6

    Google Scholar 

  • Steinbüchel A, Valentin HE (1995) Diversity of bacterial polyhydroxyalkanoic acids. FEMS Microbiol Lett 128:219–228

    Article  Google Scholar 

  • Steinbüchel A, Aerts K, Babel W, Follner C, Liebergesell M, Madkour MH, Mayer F, Pieper-Furst U, Pries A, Valentin HE, Roman W (1995) Considerations on the structure and biochemistry of bacterial polyhydroxyalkanoic acid inclusions. Can J Microbiol 41(Suppl 1):94–105

    Article  Google Scholar 

  • Taguchi S, Yamada M, Matsumoto K, Tajima K, Satoh Y, Munekata M, Ohno K, Kohda K, Shimamura T, Kambe H, Obata S (2008) A microbial factory for lactate-based polyesters using a lactate-polymerizing enzyme. Proc Natl Acad Sci U S A 105:17323–17327. doi:10.1073/pnas.0805653105

    Article  CAS  Google Scholar 

  • Timm A, Steinbüchel A (1990) Formation of polyesters consisting of medium-chain-length 3-hydroxyalkanoic acids from gluconate by Pseudomonas aeruginosa and other fluorescent pseudomonads. Appl Environ Microbiol 56:3360–3367

    CAS  Google Scholar 

  • Valentin HE, Dennis D (1997) Production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in recombinant Escherichia coli grown on glucose. J Biotechnol 58:33–38

    Article  CAS  Google Scholar 

  • Valentin HE, Mitsky TA, Mahadeo DA, Tran M, Gruys KJ (2000) Application of a propionyl coenzyme A synthetase for poly(3-hydroxypropionate-co-3-hydroxybutyrate) accumulation in recombinant Escherichia coli. Appl Environ Microbiol 66:5253–5258

    Article  CAS  Google Scholar 

  • Wang Q, Liu C, Xian M, Zhang Y, Zhao G (2012a) Biosynthetic pathway for poly(3-hydroxypropionate) in recombinant Escherichia coli. J Microbiol 50:693–697. doi:10.1007/s12275-012-2234-y

    Article  CAS  Google Scholar 

  • Wang Q, Tappel RC, Zhu C, Nomura CT (2012b) Development of a new strategy for production of medium-chain-length polyhydroxyalkanoates by recombinant Escherichia coli via inexpensive non-fatty acid feedstocks. Appl Environ Microbiol 78:519–527. doi:10.1128/AEM.07020-11

    Article  Google Scholar 

  • Yamada M, Matsumoto K, Nakai T, Taguchi S (2009) Microbial production of lactate-enriched poly[(R)-lactate-co-(R)-3-hydroxybutyrate] with novel thermal properties. Biomacromolecules 10:677–681. doi:10.1021/bm8013846

    Article  CAS  Google Scholar 

  • Yang TH, Jung YK, Kang HO, Kim TW, Park SJ, Lee SY (2011) Tailor-made type II Pseudomonas PHA synthases and their use for the biosynthesis of polylactic acid and its copolymer in recombinant Escherichia coli. Appl Microbiol Biotechnol 90:603–614. doi:10.1007/s00253-010-3077-2

    Article  CAS  Google Scholar 

  • Yang TH, Kim TW, Kang HO, Lee SH, Lee EJ, Lim SC, Oh SO, Song AJ, Park SJ, Lee SY (2010) Biosynthesis of polylactic acid and its copolymers using evolved propionate CoA transferase and PHA synthase. Biotechnol Bioeng 105:150–160

    Article  CAS  Google Scholar 

  • Zhou Q, Shi ZY, Meng DC, Wu Q, Chen JC, Chen GQ (2011) Production of 3-hydroxypropionate homopolymer and poly(3-hydroxypropionate-co-4-hydroxybutyrate) copolymer by recombinant Escherichia coli. Metab Eng 13:777–785. doi:10.1016/j.ymben.2011.10.002

    Article  CAS  Google Scholar 

  • Zhou XY, Yuan XX, Shi ZY, Meng DC, Jiang WJ, Wu LP, Chen JC, Chen GQ (2012) Hyperproduction of poly(4-hydroxybutyrate) from glucose by recombinant Escherichia coli. Microb Cell Fact 11:54. doi:10.1186/1475-2859-11-54

    Article  CAS  Google Scholar 

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Acknowledgments

This research was financially supported by a grant from the National Basic Research Program of China (2011CB707405, 2012CB725202) and grants from the National Natural Science Foundation of China (31200033) and the promotive research fund for excellent, young, and middle-aged scientists of Shandong Province (BS2012SW005).

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  1. National Glycoengineering Research Center, State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, People’s Republic of China

    Qian Wang, Qianqian Zhuang, Quanfeng Liang & Qingsheng Qi

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Wang, Q., Zhuang, Q., Liang, Q. et al. Polyhydroxyalkanoic acids from structurally-unrelated carbon sources in Escherichia coli . Appl Microbiol Biotechnol 97, 3301–3307 (2013). https://doi.org/10.1007/s00253-013-4809-x

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