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High-cell-density culture strategies for polyhydroxyalkanoate production: a review

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Journal of Industrial Microbiology & Biotechnology

Abstract

This article gives an overview of high-cell-density cultures for polyhydroxyalkanoate (PHA) production and their modes of operation for increasing productivity. High cell densities are very important in PHA production mainly because this polymer is an intracellular product accumulated in various microorganisms, so a high cellular content is needed for the polymer production. This review describes relevant results from fed-batch, repeated batch, and continuous modes of operation without and with cell recycle for the production of these polymers by microorganisms. Finally, recombinant microorganisms for PHA production, as well future directions for PHA production, are discussed.

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Abbreviations

(3HV):

3-Hydroxyvalerate

AP:

Analytical purity

(C/PA):

Carbon source/propionic acid ratio

C/N:

Carbon source sucrose or sugar cane molasses/nitrogen source urea or ammonium sulfate

DO:

Dissolved oxygen

FOS:

Fructooligosaccharides

GBL:

γ-Butyrolactone

GRP:

Waste glycerol

HCDC:

High-cell-density cultures

MM:

Mineral medium

P(3HB):

Poly(3-hydroxybutyrate)

P(3HB-4HB):

Poly(3-hydroxybutyrate–4-hydroxybutyrate)

P(3HB-4HB-3HV):

Poly(3-hydroxybutyrate–4-hydroxybutyrate–3-hydroxyvalerate)

P(3HB-co-3HV):

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)

P(3HB-co-4HB):

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)

%PHAs:

Polyhydroxyalkanoate cell content

PA:

Propionic acid

PHA:

Polyhydroxyalkanoates

PHASCL :

Short-chain-length polyhydroxyalkanoates

PHASMCL :

Medium-chain-length polyhydroxyalkanoates

r PHAS :

Productivity of polyhydroxyalkanoates

STR:

Stirred tank reactors

Xr:

Residual biomass

Xt:

Total biomass concentration

References

  1. Ahn WS, Park SJ, Lee SY (2001) Production of poly(3-hydroxybutyrate) from whey by cell recycle fed-batch culture of recombinant Escherichia coli. Biotechnol Lett 23:235–240. doi:10.1023/A:1005633418161

    Article  CAS  Google Scholar 

  2. Atlić A, Koller M, Scherzer D, Kutschera C, Grillo-Fernandes E, Horvat P, Chiellini E, Braunegg G (2011) Continuous production of poly([R]-3-hydroxybutyrate) by Cupriavidus necator in a multistage bioreactor cascade. Appl Microbiol Biotechnol 91:295–304. doi:10.1007/s00253-011-3260-0

    Article  PubMed  Google Scholar 

  3. Aragão GMF, Lindley ND, Uribelarrea JL, Pareilleux A (1996) Maintaining a controlled residual growth capacity increases the production of polyhydroxyalkanoate copolymers by Alcaligenes eutrophus. Biotechnol Lett 18:937–942

    Article  Google Scholar 

  4. Aragão GMF, Schmidell W, Ienczak JL, Schmidt FC, Dalcanton F, Fiorese ML, Rodrigues R, Deucher R, Marangoni C (2009) Preparation of polyhydroxyalkanoates from a citric residue. WO2009/149529 A1

  5. Bengtssona S, Piscob AR, Johanssona P, Lemos PC, Reis MAM (2010) Molecular weight and thermal properties of polyhydroxyalkanoates produced from fermented sugar molasses by open mixed cultures. J Biotechnol 147(3):172–179

    Article  Google Scholar 

  6. Breuer U, Terentiev Y, Kunze G, Babel W (2002) Yeasts as producers of polyhydroxyalkanoates: genetic engineering of Saccharomyces cerevisiae. Macromol Biosci 2:380–386. doi:10.1002/1616-5195(200211)

    Article  CAS  Google Scholar 

  7. Cavalheiro JMBT, Raposo SR, Almeida MCMD, Sevrin MTCC, Grandfils C, Fonseca MMR (2012) Effect of cultivation parameters on the production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and poly(3-hydroxybutyrate-4-hydroxybutyrate-3-hydroxyvalerate) by Cupriavidus necator using waste glycerol. Bioresourc Technol 111:391–397. doi:10.1016/j.biortech.2012.01.176

    Article  CAS  Google Scholar 

  8. Chen GQ (2009) A microbial polyhydroxyalkanoates (PHA) based bioand materials industry. Chem Soc Rev 38:2434–2446

    Article  PubMed  CAS  Google Scholar 

  9. Chen GQ, Zhang G, Park SJ, Lee SY (2001) Industrial scale production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). Appl Microbiol Biotechnol 57:50–55. doi:10.1007/s002530100755

    Article  PubMed  CAS  Google Scholar 

  10. Choi J, Lee SY (1997) Process analysis and economic evaluation for poly(3-hydroxybutyrate) production by fermentation. Bioprocess Eng 17:335–342. doi:10.1007/s004490050394

    Article  CAS  Google Scholar 

  11. Choi J, Lee SY, Han K (1998) Cloning of the Alcaligenes latus polyhydroxyalkanoate biosynthesis genes and use of this genes for enhanced production of poly(3-hydroxybutyrate) in Escherichia coli. Appl Environ Microbiol 64:4879–4903

    Google Scholar 

  12. Dalcanton F, Ienczak JL, Fiorese ML, Aragão GMF (2010) Produção de poli(3-hidroxibutirato) por Cupriavidus necator em meio hidrolisado de amido de arroz com suplementação de óleo de soja em diferentes temperaturas. Quim Nova 33(3):552–556. doi:10.1590/S0100-40422010000300011

    Article  CAS  Google Scholar 

  13. Dias JML, Lemos PC, Serafim LS, Oliveira C, Eiroa M, Albuquerque MGE, Ramos AM, Oliveira R, Reis MAM (2006) Recent advances in polyhydroxyalkanoate production by mixed aerobic cultures: from the substrate to the final product. Macromol Biosci 6:885–906. doi:10.1002/mabi.200600112

    Article  PubMed  CAS  Google Scholar 

  14. Diniz SC, Taciro MK, Gomez JGC, Pradella JGC (2004) High-cell-density cultivation of Pseudomonas putida IPT 046 and medium-chain-length polyhydroxyalkanoate production from sugarcane carbohydrates. Appl Biochem Biotechnol 119:51–69

    Article  PubMed  CAS  Google Scholar 

  15. Du G, Chen J, Yu J, Lun S (2001) Continuous production of poly-3-hydroxybutyrate by Ralstonia eutropha in a two-stage culture system. J Biotechnol 88:59–65. doi:10.1016/S0168-1656(01)00266-8

    Article  PubMed  CAS  Google Scholar 

  16. Fidler S, Dennis D (1992) Polyhydroxyalkanoate production in recombinant Escherichia coli. FEMS Microbiol Rev 103:231–236

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Grón S, Biedermann K, Emborg C (1995) Enzyme production in a cell recycle fermentation system evaluated by computer simulations. Bioprocess Eng 13:59–68

    Article  Google Scholar 

  19. Hahn SK, Chang YK, Lee SY (1995) Recovery and characterization of poly(3-hydroxybutyric acid) synthesized in Alcaligenes eutrophus and recombinant Escherichia coli. Appl Environ Microbiol 61:34–39

    PubMed  CAS  Google Scholar 

  20. Hanisch A (1986) Cell harvesting. In: McGregor WC (ed) Membrane separations in biotechnology. Marcel Dekker, New York

  21. Hartmann R, Hany R, Geiger T, Egli T, Witholt B, Zinn M (2004) Tailored biosynthesis of olefinic medium-chain-length poly[(R)-3-hydroxyalkanoates] in Pseudomonas putida GPo1 with improved thermal properties. Macromolecules 37:6780–6785. doi:10.1021/ma040035+

    Article  CAS  Google Scholar 

  22. 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. doi:10.1007/s00253-010-2739-4

    Article  PubMed  CAS  Google Scholar 

  23. Höffer P, Vermetteb P, Groleaua D (2011) Production and characterization of polyhydroxyalkanoates by recombinant Methylobacterium extorquens: combining desirable thermal properties with functionality. Biochem Eng J 54:26–33. doi:10.1016/j.bej.2011.01.003

    Article  Google Scholar 

  24. Huang WC, Chen SJ, Chen TL (2008) Production of hyaluronic acid by repeated batch fermentation. Biochem Eng J 40:460–464. doi:10.1016/j.bej.2008.01.021

    Article  CAS  Google Scholar 

  25. Huisman GW, Wonin E, Koning G, Preusting H, Witholt B (1992) Synthesis of poly(3-hydroxyalkanoates) by mutant and recombinant Pseudomonas strains. Appl Microbiol Biotechnol 38:1–5

    Article  CAS  Google Scholar 

  26. Ibrahim MHA, Steinbüchel A (2010) High-cell-density cyclic fed-batch fermentation of a poly(3-hydroxybutyrate)-accumulating thermophile, Chelatococcus sp. strain MW10. Appl Environ Microbiol 76(23):7890–7895. doi:10.1128/AEM.01488-10

    Article  PubMed  CAS  Google Scholar 

  27. Ienczak JL, Quines LK, Melo AA, Brandellero M, Mendes CR, Schmidell W, Aragão GMF (2011) High cell density strategy for poly(3-hydroxybutyrate) production by Cupriavidus necator. Braz J Chem Eng 28(4):585–596. doi:10.1590/S0104-66322011000400004

    CAS  Google Scholar 

  28. 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. doi:10.1016/S0141-3910(03)00227-1

    Article  CAS  Google Scholar 

  29. Khanna S, Srivastava AK (2006) Computer simulated fed-batch cultivation for over production of PHB: a comparison of simultaneous and alternate feeding of carbon and nitrogen. Biochem Eng J 27:197–203. doi:10.1016/j.bej.2005.08.006

    Article  CAS  Google Scholar 

  30. Khanna S, Srivastava AK (2008) Continuous production of poly-β-hydroxybutyrate by high-cell-density cultivation of Wautersia eutropha. J Chem Technol Biotechnol 83:799–805. doi:10.1002/jctb.1868

    Article  CAS  Google Scholar 

  31. Khanna S, Srivastava AK (2005) Repeated fed-batch cultivation of Ralstonia eutropha for poly(β-hydroxybutyrate) production. Biotechnol Lett 27:1401–1403. doi:10.1007/s10529-005-0688-2

    Article  PubMed  CAS  Google Scholar 

  32. Kim BS, Lee SC, Lee SY, Chang HN, Chang YK, Woo SI (1994) Production of poly(3-hydroxybutyric acid) by fed-batch culture of Alcaligenes eutrophus with glucose concentration control. Biotechnol Bioeng 43:892–898. doi:10.1002/bit.260430908

    Article  PubMed  CAS  Google Scholar 

  33. Klinke S, Ren Q, Witholt B, Kessler B (1999) Production of medium-chain-length by recombinant Escherichia coli poly(3-hydroxyalkanoates) from gluconate. Appl Environ Microbiol 65(2):540

    PubMed  CAS  Google Scholar 

  34. Koyama N, Doi Y (1995) Continuous production poly(3-hydrobutyrate-co-3-hydroxyvalerate) by Alcaligenes eutrophus. Biotechnol Lett 17(3):281–284

    Article  CAS  Google Scholar 

  35. Kulpreecha S, Boonruangthavorn A, Meksiriporn B, Thongchul N (2009) Inexpensive fed-batch cultivation for high poly(3-hydroxybutyrate) production by a new isolate of Bacillus megaterium. J Biosci Bioeng 107(3):240–245. doi:10.1016/j.jbiosc.2008.10.006

    Article  PubMed  CAS  Google Scholar 

  36. Leaf TA, Peterson MS, Stoup SK, Somers D, Srienc F (1996) Saccharomyces cerevisiae expressing bacterial polyhydroxybutyrate synthase produces poly-3-hydroxybutyrate. Microbiology 142:1169–1180

    Article  PubMed  CAS  Google Scholar 

  37. Lee SY (1996) Bacterial polyhydroxyalkanoates. Biotechnol Bioeng 49:1–4. doi:10.1002/(SICI)1097-0290(19960105)49:1<1:AID-BIT1>3.0.CO;2-P

    Article  PubMed  CAS  Google Scholar 

  38. Lee SY, Chang HN (1995) Production of poly(hydroxyalkanoic acid). Adv Biochem Eng Biotechnol 52:27–58

    PubMed  CAS  Google Scholar 

  39. Lee SY, Wong HH, Choi J, Lee SH, Lee SC, Chang CS (2000) Production of medium-chain-length polyhydroxyalkanoates by high-cell-density cultivation of Pseudomonas putida under phosphorus limitation. Biotechnol Bioeng 68(4):466–470. doi:10.1002/(SICI)1097-0290(20000520)68:4<466:AID-BIT12>3.0.CO;2-T

    Article  PubMed  CAS  Google Scholar 

  40. Lee WH, Loo CY, Nomura CT, Sudesh K (2008) Biosynthesis of polyhydroxyalkanoate copolymers from mixtures of plant oils and 3-hydroxyvalerate precursors. Bioresourc Technol 99:6844–6851. doi:10.1016/j.biortech.2008.01.051

    Article  CAS  Google Scholar 

  41. Leonard E, Nielsen D, Solomon K, Prather KJ (2008) Engineering microbes with synthetic biology frameworks. Trends Biotechnol 26:674–681

    Article  PubMed  CAS  Google Scholar 

  42. Liu F, Jian J, Shen X, Chung A, Chen J, Chen GQ (2012) Metabolic engineering of Aeromonas hydrophila 4AK4 for production of copolymers of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoate. Bioresourc Technol 102:8123–8129. doi:10.1016/j.biortech.2011.05.074

    Article  Google Scholar 

  43. Liu DW, Zeng RJ, Angelidaki I (2008) Enrichment and adaptation of extreme-thermophilic (70 °C) hydrogen producing bacteria to organic household solid waste by repeated batch cultivation. Int J Hydrogen Energy 33:6492–6497. doi:10.1016/j.ijhydene.2008.08.014

    Article  CAS  Google Scholar 

  44. Märkl H, Pörther R (1998) Dialysis culture. Appl Microbiol Biotechnol 50:403–414

    Article  PubMed  Google Scholar 

  45. Matsusaki H, Abe H, Doi Y (2000) Biosynthesis and properties of poly(3-hydroxybutyrate-co-3-hydroxyalkanoates) by recombinant strains of Pseudomonas sp. 61–3. Biomacromolecules 1:17–22. doi:10.1021/bm9900040

    Article  PubMed  CAS  Google Scholar 

  46. McNeil B, Harvey LM (1990) Fermentation, a practical approach. IRL, Tokyo

    Google Scholar 

  47. Meleigy SA, Khalaf MA (2009) Biosynthesis of gibberelic acid from milk permeate in repeated batch operation by a mutant Fusarium moliniforme cells immobilized on loofah sponge. Bioresour Technol 100:374–379. doi:10.1016/j.biortech.2008.06.024

    Article  PubMed  CAS  Google Scholar 

  48. Meszaros A, Bales V (1992) A contribution to optimal control of fed-batch biochemical processes. Bioprocess Eng 7:363–367. doi:10.1007/BF00369492

    Article  CAS  Google Scholar 

  49. Mothes G, Ackermann JU (2005) Synthesis of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) with a target mole fraction of 4-hydroxybutyric acid units by two-stage continuous cultivation of Delftia acidovorans P4a. Eng Life Sci 5:58–62. doi:10.1002/elsc.200420056

    Article  CAS  Google Scholar 

  50. Mukherji S, van Oudenaarden A (2009) Synthetic biology: understanding biological design from synthetic circuits. Nat Rev Genet 10:859–871. doi:10.1038/nrg2697

    PubMed  CAS  Google Scholar 

  51. Mussatto SI, Rodrigues LR, Teixeira JA (2009) β-Fructofuranosidase production by repeated batch fermentation with immobilized Aspergillus japonicas. J Ind Microbiol Biotechnol 36:923–928. doi:10.1007/s10295-009-0570-7

    Article  PubMed  CAS  Google Scholar 

  52. Oh H, Wee YJ, Yun JS, Ryu HW (2003) Lactic acid production through cell-recycle repeated-batch bioreactor. Appl Biochem Biotechnol 107:603–613

    Article  Google Scholar 

  53. Peoples OP, Sinskey AJ (1989) Poly-beta-hydroxybutyrate (PHB) biosynthesis in Alcaligenes eutrophus H16—identification and characterization of the Phb polymerase gene (phbC). J Biol Chem 264:15298–15303

    PubMed  CAS  Google Scholar 

  54. Pirt SJ (1990) The dynamics of microbial processes: a personal view. In: Poole RK, Bazin MJ, Keevil CM (eds) Microbial growth dynamics, vol 28. IRL, Tokyo, pp 1–16

  55. Poirier Y, Erard N, Petetot JM (2001) Synthesis of polyhydroxyalkanoate in the peroxisome of Saccharomyces cerevisiae by using intermediates of fatty acid β-oxidation. Appl Environ Microbiol 67:5254–5260

    Article  PubMed  CAS  Google Scholar 

  56. Poirier Y, Erard N, MacDonald-Comber PJ (2002) Synthesis of polyhydroxyalkanoate in the peroxisome of Pichia pastoris. FEMS Microbiol Lett 207:97–102

    Article  PubMed  CAS  Google Scholar 

  57. Povolo S, Toffano P, Basaglia M, Casella S (2010) Polyhydroxyalkanoates production by engineered Cupriavidus necator from waste material containing lactose. Bioresourc Technol 101:7902–7907. doi:10.1016/j.biortech.2010.05.029

    Article  CAS  Google Scholar 

  58. Pradella JGC, Taciro MK, Pataquiva AY (2010) High-cell-density poly (3-hydroxybutyrate) production from sucrose using Burkholderia sacchari culture in airlift bioreactor. Bioresourc Technol 101:8355–8360. doi:10.1016/j.biortech.2010.05.046

    Article  CAS  Google Scholar 

  59. Radmann EM, Reinehr CO, Costa JAV (2007) Optimization of the repeated batch cultivation of microalga Spirulina platensis in open raceway ponds. Aquaculture 265:118–126. doi:10.1016/j.aquaculture.2007.02.001

    Article  Google Scholar 

  60. Ramsay BA, Ramsay JA, Lomaliza K, Chavarie C, Bataille P (1990) Production of poly-(β-hydroxybutyric-co-β-hydroxyvaleric) acid copolymers. Appl Environ Microbiol 56:2093–2098

    PubMed  CAS  Google Scholar 

  61. Reddy CSK, Ghai R, Rashmi T, Kahia VC (2003) Polyhydroxyalkanoates: an overview. Bioresourc Technol 87:137–146

    Article  CAS  Google Scholar 

  62. Richardson KR (1988) Production of beta-hydroxybutyrate polymers. European Patent EP 0114086 B1

  63. 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. doi:10.1002/bit.23283

    Article  PubMed  CAS  Google Scholar 

  64. Riesenberg D (1991) High-cell-density cultivation of Escherichia coli. Curr Opin Biotechnol 2:380–384

    Article  PubMed  CAS  Google Scholar 

  65. Riesenberg D, Guthke R (1999) High-cell-density cultivation of microorganisms. Appl Microbiol Biotechnol 51:422–430. doi:10.1007/s002530051412

    Article  PubMed  CAS  Google Scholar 

  66. Rocha RCS, Silva LF, Taciro MK, Pradella JGC (2008) Production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) P(3HB-co-3HV) with a broad range of 3HV content at high yields by Burkholderia sacchari IPT 189. World J Microbiol Biotechnol 24:427–431

    Article  CAS  Google Scholar 

  67. 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(1):25–32

    Article  Google Scholar 

  68. Serafim LS, Lemos PC, Albuquerque MGE, Reis MAM (2008) Strategies for PHA production by mixed cultures and renewable waste materials. Appl Microbiol Biotechnol 81:615–628. doi:10.1007/s00253-008-1757-y

    Article  PubMed  CAS  Google Scholar 

  69. Shang L, Jiang M, Chang HN (2003) Poly(3-hydroxybutyrate) synthesis in fed-batch culture of Ralstonia eutropha with phosphate limitation under different glucose concentrations. Biotechnol Lett 25:1415–1419

    Article  PubMed  CAS  Google Scholar 

  70. Sun Z, Ramsay JA, Guay M, Ramsay BA (2007) Carbon-limited fed-batch production of medium-chain-length polyhydroxyalkanoates from nonanoic acid by Pseudomonas putida KT2440. Appl Microbiol Biotechnol 74:69–77. doi:10.1007/s00253-006-0655-4

    Article  PubMed  CAS  Google Scholar 

  71. Tan D, Xue YS, Aibaidula G, Chen GQ (2011) Unsterile and continuous production of polyhydroxybutyrate by Halomonas TD01. Bioresourc Technol 102:8130–8136. doi:10.1016/j.biortech.2011.05.068

    Article  CAS  Google Scholar 

  72. Turner C, Gregory ME, Thornhill N (1994) Closed-loop control of fed-batch cultures of recombinant Escherichia coli using on-line HPLC. Biotechnol Bioeng 44:819–829. doi:10.1002/bit.260440707

    Article  PubMed  CAS  Google Scholar 

  73. Wang F, Lee SY (1998) High cell density culture of metabolically engineered Escherichia coli for the production of poly(3-hydroxybutyrate) in a defined medium. Biotechnol Bioeng 58:325–328. doi:10.1002/(SICI)1097-0290(19980420)58:2/3<325:AID-BIT33>3.0.CO;2-8

    Article  PubMed  CAS  Google Scholar 

  74. Wong HH, Lee SY (1998) Poly(3-hydroxybutyrate) production from whey by high cell density cultivation of recombinant Escherichia coli. Appl Microbiol Biotechnol 50:30–33

    Article  PubMed  CAS  Google Scholar 

  75. Yamane T, Fukunaga M, Lee YW (1996) Increased PHB production by high-cell-density fed-batch culture of Alcaligenes latus, a growth associated PHB producer. Biotechnol Bioeng 50:197–202. doi:10.1002/(SICI)1097-0290(19960420)50:2<197:AID-BIT8>3.0.CO;2-H

    Article  PubMed  CAS  Google Scholar 

  76. Yang X, Wang B, Cui F, Tan T (2005) Production of lipase by repeated batch fermentation immobilized Rhizopus arrhizus. Process Biochem 40:2095–2103. doi:10.1016/j.procbio.2004.07.015

    Article  CAS  Google Scholar 

  77. Yee L, Blanch HW (1992) Recombinant protein expression in high cell density fed-batch cultures of Escherichia coli. Biotechnol Adv 10:1550–1556

    Article  CAS  Google Scholar 

  78. Zhang B, Carlson R, Pederson EN, Srienc F (2005) Novel synthesis routes for polyhydroxyalkanoic acids with unique properties. Polym Biocatal Biomater 900:292–301

    Article  CAS  Google Scholar 

  79. Zhu L, Zhu Y, Zhang Y, Li Y (2012) Engineering the robustness of industrial microbes through synthetic biology. Trends Microbiol 20:94–101. doi:10.1016/j.tim.2011.12.003

    Article  PubMed  CAS  Google Scholar 

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Ienczak, J.L., Schmidell, W. & de Aragão, G.M.F. High-cell-density culture strategies for polyhydroxyalkanoate production: a review. J Ind Microbiol Biotechnol 40, 275–286 (2013). https://doi.org/10.1007/s10295-013-1236-z

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