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

World Journal of Microbiology and Biotechnology

Volumn 34, Issue 6, 2018, Pages

  Kutralam Muniasamy, Gurusamy ^a   Peréz Guevara, Fermín ^a  

^a DEPARTAMENTO DE FÍSICA   (Mexico)

Author keywords

Biofuels; Medium chain length; Metabolic engineering; Mutants; PHA synthase; Phasins

Indexed keywords

BIOFUELS; GENES; MACHINERY; METABOLIC ENGINEERING; METABOLISM;

BIOTECHNOLOGICAL APPLICATIONS; FATTY ACID METABOLISM; MUTANTS; PHA PRODUCTION; PHA SYNTHASES; PHASINS; POLYHYDROXYALKANOATES; STRAIN SELECTION;

FATTY ACIDS;

BACTERIAL PROTEIN; BIOFUEL; POLYHYDROXYALKANOIC ACID;

BIOSYNTHESIS; BIOTECHNOLOGY; CHEMISTRY; CUPRIAVIDUS NECATOR; FERMENTATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; METABOLIC ENGINEERING; METABOLISM; MULTIGENE FAMILY; MUTATION;

BACTERIAL PROTEINS; BIOFUELS; BIOTECHNOLOGY; CUPRIAVIDUS NECATOR; FERMENTATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, BACTERIAL; METABOLIC ENGINEERING; METABOLIC NETWORKS AND PATHWAYS; MULTIGENE FAMILY; MUTATION; POLYHYDROXYALKANOATES;

EID: 85047527297     PISSN: 09593993     EISSN: 15730972     Source Type: Journal    
DOI: 10.1007/s11274-018-2460-5     Document Type: Review

References (121)

1. 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
2. Andreeßen C, Gerlt V, Steinbüchel A (2017) Conversion of cysteine to 3-mercaptopyruvic acid by bacterial aminotransferases. Enzyme Microb Technol 99:38–48
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. Chen GQ (2009) A microbial polyhydroxyalkanoates (PHA) based bio- and materials industry. Chem Soc Rev 38:2434–2446
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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
25. 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
26. 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
27. 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
28. 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
29. 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
30. 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
31. 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
32. 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
33. 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
34. 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
35. 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
36. 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
37. Jahns AC, Rehm BH (2012) Relevant uses of surface proteins–display on self-organized biological structures. Microb Biotechnol 5:188–202
38. Jendrossek D, Handrick R (2002) Microbial degradation of polyhydroxyalkanoates. Annu Rev Microbiol 56:403–432
39. 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
40. Jiang XR, Chen GQ (2016) Morphology engineering of bacteria for bio-production. Biotechnol Adv 34(4):435–440
41. 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
42. 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
43. 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
44. 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
45. 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
46. 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
47. 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
48. 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
49. 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
50. 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
51. 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
52. 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
53. 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
54. Lee M, Jeon BY, Oh MK (2016) Microbial production of ethanol from acetate by engineered Ralstonia eutropha. Biotechnol Bioproc Eng 21:402–407
55. Li R, Zhang H, Qi Q (2007) The production of polyhydroxyalkanoates in recombinant Escherichia coli. Biores Technol 98:2313–2320
56. 2 to higher alcohols. Science 335:1596–1596
57. 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
58. 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
59. 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
60. 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
61. 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
62. 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
63. 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
64. 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
65. 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
66. Madison LL, Huisman GW (1999) Metabolic engineering of poly (3-hydroxyalkanoates): from DNA to plastic. Microbiol Mol Biol Rev 63:21–53
67. 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
68. 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
69. 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
70. 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
71. 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
72. 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
73. 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
74. 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
75. 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
76. Nomura CT, Taguchi S (2007) PHA synthase engineering toward superbiocatalysts for custom-made biopolymers. Appl Microbiol Biotechnol 73:969–979
77. 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
78. 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
79. 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
80. 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
81. 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
82. 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
83. 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
84. 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
85. 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
86. 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
87. 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
88. 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
89. Rehm BH (2003) Polyester synthases: natural catalysts for plastics. Biochem J 376:15–33
90. Rehm BH (2006) Genetics and biochemistry of polyhydroxyalkanoate granule self-assembly: the key role of polyester synthases. Biotechnol Lett 28:207–213
91. 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
92. 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
93. 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
94. 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
95. 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
96. 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
97. 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
98. 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
99. 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
100. 2 fixation into poly (3-hydroxybutyrate) under heterotrophic condition in Ralstonia eutropha H16 based on RNA-seq and gene deletion analyses. BMC Microbiol 13:169
101. 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
102. 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
103. 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
104. 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
105. 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
106. 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
107. 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
108. 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
109. 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
110. 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
111. 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
112. 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
113. 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
114. 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
115. 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
116. 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
117. 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
118. 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
119. 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
120. 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
121. 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