Skip to main content
Log in

Genome characteristics dictate poly-R-(3)-hydroxyalkanoate production in Cupriavidus necator H16

  • Review
  • Published:
World Journal of Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Cupriavidus necator H16 is a well-recognized enterprise with efficient manufacturing machineries to produce diverse polymers belonging to polyhydroxyalkanoates (PHAs) family. The genome fingerprints, including PHA machinery proteins and fatty acid metabolism, had educated engineering strategies to enhance PHAs production. This outstanding progress has enlightened us to present an exhaustive examination of the ongoing research, addressing the great potential design of genome features towards PHA production and furthermore, we show how those acquired knowledge have been explored in other biotechnological applications. This updated-review concludes that the combination of an optimal strain selection, suitable metabolic engineering and a large-scale fermentation on oil substrates is critical to endow the ability of incorporating mcl-PHAs monomers in this organism.

Graphical Abstract

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abe T, Kobayashi T, Saito T (2005) Properties of a novel intracellular poly (3-hydroxybutyrate) depolymerase with high specific activity (PhaZd) in Wautersia eutropha H16. J Bacteriol 187:6982–6990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andreeßen C, Gerlt V, Steinbüchel A (2017) Conversion of cysteine to 3-mercaptopyruvic acid by bacterial aminotransferases. Enzyme Microb Technol 99:38–48

    Article  CAS  PubMed  Google Scholar 

  • Arikawa H, Matsumoto K (2016) Evaluation of gene expression cassettes and production of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) with a fine modulated monomer composition by using it in Cupriavidus necator. Microb Cell Fact 15:184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arikawa H, Sato S, Fujiki T, Matsumoto K (2016) A study on the relation between poly (3-hydroxybutyrate) depolymerases or oligomer hydrolases and molecular weight of polyhydroxyalkanoates accumulating in Cupriavidus necator H16. J Biotechnol 227:94–102

    Article  CAS  PubMed  Google Scholar 

  • Arikawa H, Matsumoto K, Fujiki T (2017) Polyhydroxyalkanoate production from sucrose by Cupriavidus necator strains harboring csc genes from Escherichia coli W. Appl Microbiol Biotechnol 101:7497–7507

    Article  CAS  PubMed  Google Scholar 

  • Asenjo J, Schmidt A, Andersen P, Andrews B (1995) Effect of single nutrient limitation of poly-β-hydroxybutyrate molecular weight distribution in Alcaligenes eutrophus. Biotechnol Bioeng 46:497–502

    Article  CAS  PubMed  Google Scholar 

  • Bhatia SK, Kim JH, Kim MS, Kim J, Hong JW, Hong YG, Kim HJ, Jeon JM, Kim SH, Ahn J (2018) Production of (3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymer from coffee waste oil using engineered Ralstonia eutropha. Bioproc Biosyst Eng 41:229–235

    Article  CAS  Google Scholar 

  • Bhubalan K, Lee WH, Loo CY, Yamamoto T, Tsuge T, Doi Y, Sudesh K (2008) Controlled biosynthesis and characterization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) from mixtures of palm kernel oil and 3HV-precursors. Polym Degrad Stab 93:17–23

    Article  CAS  Google Scholar 

  • Bhubalan K, Rathi DN, Abe H, Iwata T, Sudesh K (2010) Improved synthesis of P (3HB-co-3HV-co-3HHx) terpolymers by mutant Cupriavidus necator using the PHA synthase gene of Chromobacterium sp. USM2 with high affinity towards 3HV. Polym Degrad Stab 95:1436–1442

    Article  CAS  Google Scholar 

  • Bresan S, Jendrossek D (2017) New insights into PhaM-PhaC-mediated localization of polyhydroxybutyrate granules in Ralstonia eutropha H16. Appl Environ Microbiol 83:e00505-17

    Article  PubMed  PubMed Central  Google Scholar 

  • Brigham CJ, Budde CF, Holder JW, Zeng Q, Mahan AE, Rha C, Sinskey AJ (2010) Elucidation of beta-oxidation pathways in Ralstonia eutropha H16 by examination of global gene expression. J Bacteriol 192:5454–5464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brigham CJ, Speth DR, Rha C, Sinskey AJ (2012) Whole-genome microarray and gene deletion studies reveal regulation of the polyhydroxyalkanoate production cycle by the stringent response in Ralstonia eutropha H16. Appl Environ Microbiol 78:8033–8044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Budde CF, Mahan AE, Lu J, Rha C, Sinskey AJ (2010) Roles of multiple acetoacetyl coenzyme A reductases in polyhydroxybutyrate biosynthesis in Ralstonia eutropha H16. J Bacteriol 192:5319–5328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Budde CF, Riedel SL, Willis LB, Rha C, Sinskey AJ (2011) Production of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) from plant oil by engineered Ralstonia eutropha strains. Appl Environ Microbiol 77:2847–2854

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Chen JS, Colón B, Dusel B, Ziesack M, Way JC, Torella JP (2015) Production of fatty acids in Ralstonia eutropha H16 by engineering β-oxidation and carbon storage. PeerJ 3:e1468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chuah JA, Yamada M, Taguchi S, Sudesh K, Doi Y, Numata K (2013) Biosynthesis and characterization of polyhydroxyalkanoate containing 5-hydroxyvalerate units: effects of 5HV units on biodegradability, cytotoxicity, mechanical and thermal properties. Polym Degrad Stab 98:331-338

    Article  CAS  Google Scholar 

  • Clomburg JM, Contreras SC, Chou A, Siegel JB, Gonzalez R (2018) Combination of type II fatty acid biosynthesis enzymes and thiolases supports a functional β-oxidation reversal. Metab Eng 45:11–19

    Article  CAS  PubMed  Google Scholar 

  • Crépin L, Lombard E, Guillouet SE (2016) Metabolic engineering of Cupriavidus necator for heterotrophic and autotrophic alka(e)ne production. Metab Eng 37:92–101

    Article  CAS  PubMed  Google Scholar 

  • Dennis D, McCoy M, Stangl A, Valentin H, Wu Z (1998) Formation of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) by PHA synthase from Ralstonia eutropha. J Biotechnol 64:177–186

    Article  CAS  PubMed  Google Scholar 

  • Deziel E, Lepine F, Milot S, Villemur R (2003) rhlA is required for the production of a novel biosurfactant promoting swarming motility in Pseudomonas aeruginosa: 3-(3-hydroxyalkanoyloxy) alkanoic acids (HAAs), the precursors of rhamnolipids. Microbiology 149:2005–2013

    Article  CAS  PubMed  Google Scholar 

  • Doberstein C, Grote J, Wübbeler JH, Steinbuechel A (2014) Polythioester synthesis in Ralstonia eutropha H16: novel insights into 3, 3′-thiodipropionic acid and 3, 3′-dithiodipropionic acid catabolism. J Biotechnol 184:187–198

    Article  CAS  PubMed  Google Scholar 

  • Doi Y, Segawa A, Kunioka M (1990) Biosynthesis and characterization of poly (3-hydroxybutyrate-co-4-hydroxybutyrate) in Alcaligenes eutrophus. Int J Biol Macromol 12:106–111

    Article  CAS  PubMed  Google Scholar 

  • Ewering C, Heuser F, Benölken JK, Brämer CO, Steinbüchel A (2006) Metabolic engineering of strains of Ralstonia eutropha and Pseudomonas putida for biotechnological production of 2-methylcitric acid. Metab Eng 8:587–602

    Article  CAS  PubMed  Google Scholar 

  • Fukui T, Doi Y (1998) Efficient production of polyhydroxyalkanoates from plant oils by Alcaligenes eutrophus and its recombinant strain. Appl Microbiol Biotechnol 49:333–336

    Article  CAS  PubMed  Google Scholar 

  • Fukui T, Kichise T, Yoshida Y, Doi Y (1997) Biosynthesis of poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxy-heptanoate) terpolymers by recombinant Alcaligenes eutrophus. Biotechnol Lett 19:1093–1097

    Article  CAS  Google Scholar 

  • Fukui T, Chou K, Harada K, Orita I, Nakayama Y, Bamba T, Nakamura S, Fukusaki E (2013) Metabolite profiles of polyhydroxyalkanoate-producing Ralstonia eutropha H16. Metabolomics 10:190–202

    Article  CAS  Google Scholar 

  • Galindo E, Peña C, Núñez C, Segura D, Espín G (2007) Molecular and bioengineering strategies to improve alginate and polydydroxyalkanoate production by Azotobacter vinelandii. Microb Cell Fact 6:7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Grousseau E, Lu J, Gorret N, Guillouet SE, Sinskey AJ (2014) Isopropanol production with engineered Cupriavidus necator as bioproduction platform. Appl Microbiol Biotechnol 98:4277–4290

    Article  CAS  PubMed  Google Scholar 

  • Haywood G, Anderson A, Dawes E (1989) The importance of PHB-synthase substrate specificity in polyhydroxyalkanoate synthesis by Alcaligenes eutrophus. FEMS Microbiol Lett 57:1–6

    Article  CAS  Google Scholar 

  • Heath RJ, Jackowski S, Rock CO (2002) Fatty acid and phospholipid metabolism in prokaryotes. In: Vance JE, Vance DE (eds) Biochemistry of lipids, lipoproteins and membranes, 4th edn. Elsevier, New York, pp 55–92

    Chapter  Google Scholar 

  • Hoefel T, Wittmann E, Reinecke L, Weuster-Botz D (2010) Reaction engineering studies for the production of 2-hydroxyisobutyric acid with recombinant Cupriavidus necator H 16. Appl Microbiol Biotechnol 88:477–484

    Article  CAS  PubMed  Google Scholar 

  • Insomphun C, Mifune J, Orita I, Numata K, Nakamura S, Fukui T (2013) Modification of beta-oxidation pathway in Ralstonia eutropha for production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from soybean oil. J Biosci Bioeng 117:184–190

    Article  CAS  PubMed  Google Scholar 

  • Insomphun C, Xie H, Mifune J, Kawashima Y, Orita I, Nakamura S, Fukui T (2015) Improved artificial pathway for biosynthesis of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) with high C6-monomer composition from fructose in Ralstonia eutropha. Metab Eng 27:38–45

    Article  CAS  PubMed  Google Scholar 

  • Jahns AC, Rehm BH (2009) Tolerance of the Ralstonia eutropha class I polyhydroxyalkanoate synthase for translational fusions to its C terminus reveals a new mode of functional display. Appl Environ Microbiol 75:5461–5466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jahns AC, Rehm BH (2012) Relevant uses of surface proteins–display on self-organized biological structures. Microb Biotechnol 5:188–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jendrossek D, Handrick R (2002) Microbial degradation of polyhydroxyalkanoates. Annu Rev Microbiol 56:403–432

    Article  CAS  PubMed  Google Scholar 

  • Jeon JM, Brigham CJ, Kim YH, Kim HJ, Yi DH, Kim H, Rha C, Sinskey AJ, Yang YH (2014) Biosynthesis of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate)(P (HB-co-HHx)) from butyrate using engineered Ralstonia eutropha. Appl Microbiol Biotechnol 98:5461–5469

    Article  CAS  PubMed  Google Scholar 

  • Jiang XR, Chen GQ (2016) Morphology engineering of bacteria for bio-production. Biotechnol Adv 34(4):435–440

    Article  CAS  PubMed  Google Scholar 

  • Juengert JR, Borisova M, Mayer C, Wolz C, Brigham CJ, Sinskey AJ, Jendrossek D (2017) Absence of ppGpp leads to increased mobilization of intermediately accumulated poly (3-hydroxybutyrate) in Ralstonia eutropha H16. Appl Environ Microbiol 83:e00755-17

    Article  PubMed  PubMed Central  Google Scholar 

  • Kahar P, Tsuge T, Taguchi K, Doi Y (2004) High yield production of polyhydroxyalkanoates from soybean oil by Ralstonia eutropha and its recombinant strain. Polym Degrad Stab 83:79–86

    Article  CAS  Google Scholar 

  • Karafin M, Romagnoli M, Fink DL, Howard T, Rau R, Milstone AM, Carroll KC (2010) Fatal infection caused by Cupriavidus gilardii in a child with aplastic anemia. J Clin Microbiol 48:1005–1007

    Article  PubMed  PubMed Central  Google Scholar 

  • Kawashima Y, Cheng W, Mifune J, Orita I, Nakamura S, Fukui T (2012) Characterization and functional analyses of R-specific enoyl coenzyme A hydratases in polyhydroxyalkanoate-producing Ralstonia eutropha. Appl Environ Microbiol 78:493–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawashima Y, Orita I, Nakamura S, Fukui T (2015) Compositional regulation of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) by replacement of granule-associated protein in Ralstonia eutropha. Microb Cell Fact 14:187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kek YK, Lee WH, Sudesh K (2008) Efficient bioconversion of palm acid oil and palm kernel acid oil to poly (3-hydroxybutyrate) by Cupriavidus necator. Can J Chem 86:533–539

    Article  CAS  Google Scholar 

  • Kim J, Kim YJ, Choi SY, Lee SY, Kim KJ (2017a) Crystal structure of Ralstonia eutropha polyhydroxyalkanoate synthase C-terminal domain and reaction mechanisms. Biotechnol J 12:1600648

    Article  CAS  Google Scholar 

  • Kim YJ, Choi SY, Kim J, Jin KS, Lee SY, Kim KJ (2017b) Structure and function of the N-terminal domain of Ralstonia eutropha polyhydroxyalkanoate synthase, and the proposed structure and mechanisms of the whole enzyme. Biotechnol J 12:1600649

    Article  CAS  Google Scholar 

  • Kobayashi T, Shiraki M, Abe T, Sugiyama A, Saito T (2003) Purification and properties of an intracellular 3-hydroxybutyrate-oligomer hydrolase (PhaZ2) in Ralstonia eutropha H16 and its identification as a novel intracellular poly (3-hydroxybutyrate) depolymerase. J Bacteriol 185:3485–3490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi T, Uchino K, Abe T, Yamazaki Y, Saito T (2005) Novel intracellular 3-hydroxybutyrate-oligomer hydrolase in Wautersia eutropha H16. J Bacteriol 187:5129–5135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuchta K, Chi L, Fuchs H, Pötter M, Steinbüchel A (2007) Studies on the influence of phasins on accumulation and degradation of PHB and nanostructure of PHB granules in Ralstonia eutropha H16. Biomacromol 8:657–662

    Article  CAS  Google Scholar 

  • Langevin S, Vincelette J, Bekal S, Gaudreau C (2011) First case of invasive human infection caused by Cupriavidus metallidurans. J Clin Microbiol 49:744–745

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee WH, Loo CY, Nomura CT, Sudesh K (2008) Biosynthesis of polyhydroxyalkanoate copolymers from mixtures of plant oils and 3-hydroxyvalerate precursors. Bioresour Technol 99:6844–6851

    Article  CAS  PubMed  Google Scholar 

  • Lee M, Jeon BY, Oh MK (2016) Microbial production of ethanol from acetate by engineered Ralstonia eutropha. Biotechnol Bioproc Eng 21:402–407

    Article  CAS  Google Scholar 

  • Li R, Zhang H, Qi Q (2007) The production of polyhydroxyalkanoates in recombinant Escherichia coli. Biores Technol 98:2313–2320

    Article  CAS  Google Scholar 

  • Li H, Opgenorth PH, Wernick DG, Rogers S, Wu TY, Higashide W, Malati P, Huo YX, Cho KM, Liao JC (2012) Integrated electromicrobial conversion of CO2 to higher alcohols. Science 335:1596–1596

    Article  CAS  PubMed  Google Scholar 

  • Lindenkamp N, Peplinski K, Volodina E, Ehrenreich A, Steinbuchel A (2010) Impact of multiple beta-ketothiolase deletion mutations in Ralstonia eutropha H16 on the composition of 3-mercaptopropionic acid-containing copolymers. Appl Environ Microbiol 76:5373–5378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindenkamp N, Volodina E, Steinbüchel A (2012) Genetically modified strains of Ralstonia eutropha H16 with β-ketothiolase gene deletions for production of copolyesters with defined 3-hydroxyvaleric acid contents. Appl Environ Microbiol 78:5375–5383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindenkamp N, Schürmann M, Steinbüchel A (2013) A propionate CoA-transferase of Ralstonia eutropha H16 with broad substrate specificity catalyzing the CoA thioester formation of various carboxylic acids. Appl Microbiol Biotechnol 97:7699–7770

    Article  CAS  PubMed  Google Scholar 

  • López-Cuellar M, Alba-Flores J, Rodríguez JG, Pérez-Guevara F (2011) Production of polyhydroxyalkanoates (PHAs) with canola oil as carbon source. Int J Biol Macromol 48:74–80

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Brigham CJ, Gai CS, Sinske AJ (2012) Studies on the production of branched-chain alcohols in engineered Ralstonia eutropha. Appl Microbiol Biotechnol 96:283–297

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Brigham CJ, Rha C, Sinskey AJ (2013) Characterization of an extracellular lipase and its chaperone from Ralstonia eutropha H16. Appl Microbiol Biotechnol 97:2443–2454

    Article  CAS  PubMed  Google Scholar 

  • Lütke-Eversloh T, Steinbüchel A (2003) Novel precursor substrates for polythioesters (PTE) and limits of PTE biosynthesis in Ralstonia eutropha. FEMS Microbiol Lett 221:191–196

    Article  CAS  PubMed  Google Scholar 

  • Lütke-Eversloh T, Bergander K, Luftmann H, Steinbüchel A (2001) Biosynthesis of poly (3-hydroxybutyrate-co-3-mercaptobutyrate) as a sulfur analogue to poly (3-hydroxybutyrate)(PHB). Biomacromol 2:1061–1065

    Article  CAS  Google Scholar 

  • Madden LA, Anderson AJ, Shah DT, Asrar J (1999) Chain termination in polyhydroxyalkanoate synthesis: involvement of exogenous hydroxy-compounds as chain transfer agents. Int J Biol Macromol 25:43–53

    Article  CAS  PubMed  Google Scholar 

  • Madison LL, Huisman GW (1999) Metabolic engineering of poly (3-hydroxyalkanoates): from DNA to plastic. Microbiol Mol Biol Rev 63:21–53

    CAS  PubMed  PubMed Central  Google Scholar 

  • Magomedova Z, Grecu A, Sensen CW, Schwab H, Heidinger P (2016) Characterization of two novel alcohol short-chain dehydrogenases/reductases from Ralstonia eutropha H16 capable of stereoselective conversion of bulky substrates. J Biotechnol 221:78–90

    Article  CAS  PubMed  Google Scholar 

  • Marc J, Grousseau E, Lombard E, Sinskey AJ, Gorret N, Guillouet SE (2017) Over expression of GroESL in Cupriavidus necator for heterotrophic and autotrophic isopropanol production. Metab Eng 42:74–84

    Article  CAS  PubMed  Google Scholar 

  • Mezzina MP, Wetzler DE, de Almeida A, Dinjaski N, Prieto MA, Pettinari MJ (2015) A phasin with extra talents: a polyhydroxyalkanoate granule-associated protein has chaperone activity. Environ Microbiol 17:1765–1776

    Article  CAS  PubMed  Google Scholar 

  • Mifune J, Nakamura S, Fukui T (2008) Targeted engineering of Cupriavidus necator chromosome for biosynthesis of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) from vegetable oil. Can J Chem 86:621–627

    Article  Google Scholar 

  • Mifune J, Nakamura S, Fukui T (2010) Engineering of pha operon on Cupriavidus necator chromosome for efficient biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) from vegetable oil. Polym Degrad Stab 95:1305–1312

    Article  CAS  Google Scholar 

  • Müller J, MacEachran D, Burd H, Sathitsuksanoh N, Bi C, Yeh YC, Lee TS, Hillson NJ, Chhabra SR, Singer SW (2013) Engineering of Ralstonia eutropha H16 for autotrophic and heterotrophic production of methyl ketones. Appl Environ Microbiol 79:4433–4439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murugan P, Chhajer P, Kosugi A, Arai T, Brigham CJ, Sudesh K (2016) Production of P (3HB-co-3HHx) with controlled compositions by recombinant Cupriavidus necator Re2058/pCB113 from renewable resources. Clean Soil Air Water 44:1234–1241

    Article  CAS  Google Scholar 

  • Murugan P, Gan CY, Sudesh K (2017) Biosynthesis of P (3HB-co-3HHx) with improved molecular weights from a mixture of palm olein and fructose by Cupriavidus necator Re2058/pCB113. Int J Biol Macromol 102:1112–1119

    Article  CAS  PubMed  Google Scholar 

  • Ng KS, Wong YM, Tsuge T, Sudesh K (2011) Biosynthesis and characterization of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymers using jatropha oil as the main carbon source. Proc Biochem 46:1572–1578

    Article  CAS  Google Scholar 

  • Nomura CT, Taguchi S (2007) PHA synthase engineering toward superbiocatalysts for custom-made biopolymers. Appl Microbiol Biotechnol 73:969–979

    Article  CAS  PubMed  Google Scholar 

  • Oda T, Oda K, Yamamoto H, Matsuyama A, Ishii M, Igarashi Y, Nishihara H (2013) Hydrogen-driven asymmetric reduction of hydroxyacetone to (R)-1, 2-propanediol by Ralstonia eutropha transformant expressing alcohol dehydrogenase from Kluyveromyces lactis. Microb Cell Fact 12:2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park SJ, Jang YA, Lee H, Park AR, Yang JE, Shin J, Oh YH, Song BK, Jegal J, Lee SH (2013) Metabolic engineering of Ralstonia eutropha for the biosynthesis of 2-hydroxyacid-containing polyhydroxyalkanoates. Metab Eng 20:20–28

    Article  CAS  PubMed  Google Scholar 

  • Peoples OP, Sinskey AJ (1989) Poly-beta-hydroxybutyrate biosynthesis in Alcaligenes eutrophus H16. Characterization of the genes encoding beta-ketothiolase and acetoacetyl-CoA reductase. J Biol Chem 264:15293–15297

    CAS  PubMed  Google Scholar 

  • Pfeiffer D, Jendrossek D (2011) Interaction between poly(3-hydroxybutyrate) granule-associated proteins as revealed by two-hybrid analysis and identification of a new phasin in Ralstonia eutropha H16. Microbiology 157:2795–2807

    Article  CAS  Google Scholar 

  • Pfeiffer D, Jendrossek D (2012) Localization of poly(3-Hydroxybutyrate) (PHB) granule-associated proteins during PHB granule formation and identification of two new phasins, PhaP6 and PhaP7, in Ralstonia eutropha H16. J Bacteriol 194:5909–5921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pfeiffer D, Jendrossek D (2014) PhaM is the physiological activator of poly (3-hydroxybutyrate)(PHB) synthase (PhaC1) in Ralstonia eutropha. Appl Environ Microbiol 80:555–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pham TH, Webb JS, Rehm BH (2004) The role of polyhydroxyalkanoate biosynthesis by Pseudomonas aeruginosa in rhamnolipid and alginate production as well as stress tolerance and biofilm formation. Microbiology 150:3405–3413

    Article  CAS  PubMed  Google Scholar 

  • Pohlmann A, Fricke WF, Reinecke F, Kusian B, Liesegang H, Cramm R, Eitinger T, Ewering C, Pötter M, Schwartz E (2006) Genome sequence of the bioplastic-producing “Knallgas” bacterium Ralstonia eutropha H16. Nat Biotechnol 24:1257–1262

    Article  PubMed  Google Scholar 

  • Potter M, Muller H, Reinecke F, Wieczorek R, Fricke F, Bowien B, Friedrich B, Steinbuchel A (2004) The complex structure of polyhydroxybutyrate (PHB) granules: four orthologous and paralogous phasins occur in Ralstonia eutropha. Microbiology 150:2301–2311

    Article  CAS  PubMed  Google Scholar 

  • Potter M, Muller H, Steinbuchel A (2005) Influence of homologous phasins (PhaP) on PHA accumulation and regulation of their expression by the transcriptional repressor PhaR in Ralstonia eutropha H16. Microbiology 151:825–833

    Article  CAS  Google Scholar 

  • Przybylski D, Rohwerder T, Harms H, Yaneva N, Müller RH (2013) Synthesis of the building block 2-hydroxyisobutyrate from fructose and butyrate by Cupriavidus necator H16. Appl Microbiol Biotechnol 97:8875–8885

    Article  CAS  PubMed  Google Scholar 

  • Rathinasabapathy A, Ramsay BA, Ramsay JA, Pérez-Guevara F (2014) A feeding strategy for incorporation of canola derived medium-chain-length monomers into the PHA produced by wild-type Cupriavidus necator. World J Microbiol Biotechnol 30:1409–1416

    Article  CAS  PubMed  Google Scholar 

  • Rehm BH (2003) Polyester synthases: natural catalysts for plastics. Biochem J 376:15–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rehm BH (2006) Genetics and biochemistry of polyhydroxyalkanoate granule self-assembly: the key role of polyester synthases. Biotechnol Lett 28:207–213

    Article  CAS  PubMed  Google Scholar 

  • Rehm BH, Steinbüchel A (2002) Polyhydroxyalkanoate (PHA) synthases: the key enzymes of PHA synthesis. In: Doi Y, Steinbüchel A (eds) Biopolymers, vol 3a. Wiley-VCH, Weinheim, pp 173–215

    Google Scholar 

  • Reinecke F, Steinbuchel A (2009) Ralstonia eutropha strain H16 as model organism for PHA metabolism and for biotechnological production of technically interesting biopolymers. J Mol Microbiol Biotechnol 16:91–108

    Article  CAS  PubMed  Google Scholar 

  • Riedel SL, Bader J, Brigham CJ, Budde CF, Yusof ZAM, Rha C, Sinskey AJ (2012) Production of poly (3- hydroxybutyrate-co-3-hydroxyhexanoate) by Ralstonia eutropha in high cell density palm oil fermentations. Biotechnol Bioeng 109:74–83

    Article  CAS  PubMed  Google Scholar 

  • Ryu HW, Hahn SK, Chang YK, Chang HN (1997) Production of poly (3-hydroxybutyrate) by high cell density fed-batch culture of Alcaligenes eutrophus with phosphate limitation. Biotechnol Bioeng 55:28–32

    Article  CAS  PubMed  Google Scholar 

  • Saegusa H, Shiraki M, Kanai C, Saito T (2001) Cloning of an intracellular poly[D(-)-3-hydroxybutyrate] depolymerase gene from Ralstonia eutropha H16 and characterization of the gene product. J Bacteriol 183:94–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sato S, Fujiki T, Matsumoto K (2013) Construction of a stable plasmid vector for industrial production of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) by a recombinant Cupriavidus necator H16 strain. J Biosci Bioeng 116:677–681

    Article  CAS  PubMed  Google Scholar 

  • Sato S, Maruyama H, Fujiki T, Matsumoto K (2015) Regulation of 3-hydroxyhexanoate composition in PHBH synthesized by recombinant Cupriavidus necator H16 from plant oil by using butyrate as a co-substrate. J Biosci Bioeng 120:246–251

    Article  CAS  PubMed  Google Scholar 

  • Schwartz E, Henne A, Cramm R, Eitinger T, Friedrich B, Gottschalk G (2003) Complete nucleotide sequence of pHG1: a Ralstonia eutropha H16 megaplasmid encoding key enzymes of H2-based lithoautotrophy and anaerobiosis. J Mol Biol 332:369–383

    Article  CAS  PubMed  Google Scholar 

  • Shi F, Ashby R, Gross RA (1996) Use of poly (ethylene glycol) to regulate poly (3-hydroxybutyrate) molecular weight during Alcaligenes eutrophus cultivations. Macromolecules 29:7753–7758

    Article  CAS  Google Scholar 

  • Shimizu R, Chou K, Orita I, Suzuki Y, Nakamura S, Fukui T (2013) Detection of phase-dependent transcriptomic changes and Rubisco-mediated CO2 fixation into poly (3-hydroxybutyrate) under heterotrophic condition in Ralstonia eutropha H16 based on RNA-seq and gene deletion analyses. BMC Microbiol 13:169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sichwart S, Hetzler S, Broker D, Steinbuchel A (2011) Extension of the substrate utilization range of Ralstonia eutropha strain H16 by metabolic engineering to include mannose and glucose. Appl Environ Microbiol 77:1325–1334

    Article  CAS  PubMed  Google Scholar 

  • Sim SJ, Snell D, Hogan SA, Stubbe J, Rha C, Sinskey AJ (1997) PHA synthase activity controls the molecular weight and polydispersity of polyhydroxybutyrate in vivo. Nat Biotechnol 15:63–67

    Article  CAS  PubMed  Google Scholar 

  • Slater S, Houmiel KL, Tran M, Mitsky TA, Taylor NB, Padgette SR, Gruys KJ (1998) Multiple β-ketothiolases mediate poly (β-hydroxyalkanoate) copolymer synthesis in Ralstonia eutropha. J Bacteriol 180:1979–1987

    CAS  PubMed  PubMed Central  Google Scholar 

  • Steinbüchel A, Schlegel HG (1989) Excretion of pyruvate by mutants of Alcaligenes eutrophus, which are impaired in the accumulation of poly (β-hydroxybutyric acid) (PHB), under conditions permitting synthesis of PHB. Appl Microbiol Biotechnol 31:168–175

    Article  Google Scholar 

  • Sznajder A, Jendrossek D (2014) To be or not to be a poly (3-hydroxybutyrate)(PHB) depolymerase: PhaZd1 (PhaZ6) and PhaZd2 (PhaZ7) of Ralstonia eutropha, highly active PHB depolymerases with no detectable role in mobilization of accumulated PHB. Appl Environ Microbiol 80:4936–4946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timm A, Steinbüchel A (1992) Cloning and molecular analysis of the poly (3-hydroxyalkanoic acid) gene locus of Pseudomonas aeruginosa PAO1. Eur J Biochem 209:15–30

    Article  CAS  PubMed  Google Scholar 

  • Timm A, Byrom D, Steinbüchel A (1992) Formation of blends of various poly (3-hydroxyalkanoic acids) by a recombinant strain of Pseudomonas oleovorans. Appl Microbiol Biotechnol 33:296–301

    Article  Google Scholar 

  • Uchino K, Saito T, Gebauer B, Jendrossek D (2007) Isolated poly(3-hydroxybutyrate) (PHB) granules are complex bacterial organelles catalyzing formation of PHB from acetyl coenzyme A (CoA) and degradation of PHB to acetyl-CoA. J Bacteriol 189:8250–8256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uchino K, Saito T, Jendrossek D (2008) Poly (3-hydroxybutyrate) (PHB) depolymerase PhaZa1 is involved in mobilization of accumulated PHB in Ralstonia eutropha H16. Appl Environ Microbiol 74:1058–1063

    Article  CAS  PubMed  Google Scholar 

  • Ushimaru K, Motoda Y, Numata K, Tsuge T (2014) Phasin proteins activate Aeromonas caviae polyhydroxyalkanoate (PHA) synthase but not Ralstonia eutropha PHA synthase. Appl Environ Microbiol 80:2867–2873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Valdés J, Kutralam-Muniasamy G, Vergara-Porras B, Marsch R, Pérez-Guevara F, López-Cuellar M (2018) Heterologous expression of phaC2 gene and poly-3-hydroxyalkanoate production by recombinant Cupriavidus necator strains using canola oil as carbon source. New Biotechnol 40:200–206

    Article  CAS  Google Scholar 

  • Verlinden RAJ, Hill DJ, Kenward MA, Williams CD, Piotrowska-Seget Z, Radecka IK (2011) Production of polyhydroxyalkanoates from waste frying oil by Cupriavidus necator. AMB express 1:11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volodina E, Raberg M, Steinbüchel A (2016) Engineering the heterotrophic carbon sources utilization range of Ralstonia eutropha H16 for applications in biotechnology. Crit Rev Biotechnol 36:978–991

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Yang P, Xian M, Yang Y, Liu C, Xue Y, Zhao G (2013) Biosynthesis of poly (3-hydroxypropionate-co-3-hydroxybutyrate) with fully controllable structures from glycerol. Biores Technol 142:741–744

    Article  CAS  Google Scholar 

  • Wei DX, Chen CB, Fang G, Li SY, Chen GQ (2011) Application of polyhydroxyalkanoate binding protein PhaP as a bio-surfactant. Appl Microbiol Biotechnol 91:1037–1047

    Article  CAS  PubMed  Google Scholar 

  • Wenning L, Stöveken N, Wübbeler JH, Steinbüchel A (2016) Substrate and cofactor range differences of two cysteine dioxygenases from Ralstonia eutropha H16. Appl Environ Microbiol 82:910–921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong YM, Brigham CJ, Rha C, Sinskey AJ, Sudesh K (2012) Biosynthesis and characterization of polyhydroxyalkanoate containing high 3-hydroxyhexanoate monomer fraction from crude palm kernel oil by recombinant Cupriavidus necator. Biores Technol 121:320–327

    Article  CAS  Google Scholar 

  • Wübbeler JH, Raberg M, Brandt U, Steinbüchel A (2010) Dihydrolipoamide dehydrogenases of Advenella mimigardefordensis and Ralstonia eutropha catalyze cleavage of 3, 3′-dithiodipropionic acid into 3-mercaptopropionic acid. Appl Environ Microbiol 76:7023–7028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • York GM, Stubbe J, Sinskey AJ (2001) New insight into the role of the PhaP phasin of Ralstonia eutropha in promoting synthesis of polyhydroxybutyrate. J Bacteriol 183:2394–2397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • York GM, Stubbe J, Sinskey AJ (2002) The Ralstonia eutropha PhaR protein couples synthesis of the PhaP phasin to the presence of polyhydroxybutyrate in cells and promotes polyhydroxybutyrate production. J Bacteriol 184:59–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • York GM, Lupberger J, Tian J, Lawrence AG, Stubbe J, Sinskey AJ (2003) Ralstonia eutropha H16 encodes two and possibly three intracellular poly[D-(-)-3-hydroxybutyrate] depolymerase genes. J Bacteriol 185:3788–3794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to recognize Dr. Madel Lopez Cuellar Rocio and Dr. Arthi Rathinasabapathy for their appreciative contributions in the investigations conducted in our laboratory. This work is financially supported by CONACyT (CB-2014-01; 236285 and Fronteras de la Ciencia 2015-1: 016). The authors thank Miguel Martinez Roque and Juan Corona-Hernandez for their artwork contribution.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fermín Peréz-Guevara.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kutralam-Muniasamy, G., Peréz-Guevara, F. Genome characteristics dictate poly-R-(3)-hydroxyalkanoate production in Cupriavidus necator H16. World J Microbiol Biotechnol 34, 79 (2018). https://doi.org/10.1007/s11274-018-2460-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11274-018-2460-5

Keywords

Navigation