본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Journal of microbiology and biotechnology v.15 no.1, 2005년, pp.206 - 215   피인용횟수: 4

Short-Chain-Length Polyhydroxyalkanoates: Synthesis in Metabolically Engineered Escherichia coli and Medical Applications

PARK, SI-JAE    (Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering and BioProcess Engineering Research Center   ); CHOI, JONG-IL    (Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering and BioProcess Engineering Research Center   ); LEE, SANG-YUP    (Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering and BioProcess Engineering Research Center  );
  • 초록

    Polyhydroxyalkanoates (PHAs) are homo or hetero polyesters of (R)-hydroxyalkanoates accumulated in various microorganisms under growth-limiting condition in the presence of excess carbon source. They have been suggested as biodegradable substitutes for chemically synthesized polymers. Recombinant Escherichia coli is one of the promising host strains for the economical production of PHAs, and has been extensively investigated for the process development. The heterologous PHA biosynthetic pathways have been established through the metabolic engineering and inherent metabolic pathways of E. coli have been redirected to supply PHA precursors. Fermentation strategies for cultivating these recombinant E. coli strains have also been developed for the efficient production of PHAs. Nowadays, short-chain-length (SCL) PHAs are being re-invited due to its improved mechanical properties and possible applications in the biomedical area. In this article, recent advances in the development of metabolically engineered E. coli strains for the enhanced production of SCL-PHAs are reviewed. Also, medical applications of SCL-PHAs are discussed.


  • 주제어

    Short-chain-length PHA .   E.   coli .   metabolic.  

  • 참고문헌 (70)

    1. Brophy, M. R. and P. B. Deasy. 1986 In vitro and in vivo studies on biodegradable polyester microparticles containing sulphamethiazole. Int. J. Pharm. 29: 223- 231 
    2. Choi. J. and S. Y Lee. 2000. Economic consideration in the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by bacterial fermentation. Appl. Microbiol. Biotechnol. 53: 646-649 
    3. Deng, Y., K. Zhao, X. Zhang, P. Hu, and G. Q. Chen. 2002. Study on the three-dimensional proliferation of rabbit articular cartilage-derived chondrocytes on polyhydroxyalkanoate scaffolds. Biomaterials 23: 4049- 4056 
    4. Han, M. J., S. S. Yoon, and S. Y. Lee. 2001. Proteome analysis of metabolically engineered Escherichia coli producing poly(3-hydroxybutyrate). J. Bacteriol. 183: 301- 308 
    5. Haywood, G. W., A. J. Anderson, G. A. Williams, E. A. Dawes, and D. F. Ewing. 1991. Accumulation of a poly(hydroxyalkanoate) copolymer containing primarily 3-hydroxy valerate from simple carbohydrate substrates by Rhodococcus sp. NCIMB 40126. Int. J. Biol. Macromol. 13: 83- 87 
    6. Hong, S. H., S. J. Park, S. Y. Moon, J. P. Park, and S. Y Lee. 2003. In silico prediction and validation of the importance of Entner-Doudorff pathway in poly(3-hydroxybutyrate) production by metabolically engineered Escherichia coli. Biotechnol. Bioeng. 83: 854- 863 
    7. Kusaka, S., T. Iwata, and Y. Doi. 1998. Microbial synthesis and physical properties of ultra-high-molecular-weight poly[(R)-3-hydroxybutyrate]. J. Macromol. Sci. Pure Appl. Chem. A35: 319-335. 
    8. Kusaka, S., T. Iwata, and Y. Doi. 1999. Properties and biodegradability of ultra-high-molecular-weight poly[(R)-3-hydroxybutyrate] produced by a recombinant Escerichia coli. Int. J. Biol. Macromol. 25: 87-94. 
    9. Lee, I. Y., M. K. Kim, Y. H. Park, and S. Y. Lee. 1996. Regulatory effects of cellular nicotinamide nucleotide and enzyme activities on poly(3-hydroxybutyrate) synthesis in recombinant Escherichia coli. Biotechnol. Bioeng. 52: 707-712 
    10. Lee, S. Y. 1996. Bacterial polyhydroxyalkanoates. Biotechnol. Bioeng. 49: 1- 14 
    11. Lee, S. Y. 1996. Plastic bacteria? Progress and prospects for polyhydroxyalkanoate production in bacteria. Trends Biotechnol. 14: 431- 438 
    12. Liebergesell, M., E. Hustede, A. Timm, A. Steinbuchel, R. C. Fuller, R. W. Lenz, and H. G. Schlegel. 1991. Formation of poly(3-hydroxyalkanoates) by phototrophic and chemolithotrophic bacteria. Arch. Microbiol. 155: 415- 421 
    13. Maloy, S. R. and W. D. Nunn. 1981. Role of gene fadR in Escherichia coli acetate metabolism. J. Bacteriol. 148: 83-90 
    14. Matsusaki, H., H. Abe, and Y. Doi. 2000. Biosynthesis and properties of poly(3-hydroxybutyrate-co-3-hydroxyalkanoates) by recombinant strains of Pseudomonas sp. 61-3. Biomacromolecules 1: 17- 22 
    15. Matsusaki, H., H. Abe, K. Taguchi, T. Fukui, and Y. Doi. 2000. Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyalkanoates) by recombinant bacteria expressing the PHA synthase gene phaCl from Pseudomonas sp. 61-3. Appl. Microbiol. Biotechnol. 53: 401-419 
    16. Song, S., H. Silke, and A. Steinbiichel. 1999. Production of poly(4-hydroxybutyric acid) by fed-batch cultures of recombinant strains of Escherichia coli. Biotechnol. Lett. 21: 193-197 
    17. Steinbuchel, A. and H. E. Valentin. 1995. Diversity of bacterial polyhydroxyalkanoic acid. FEMS Microbiol. Lett. 128: 219- 228 
    18. Volova, T., E. Shishatskaya, V. Sevastianov, S. Efremov, and O. Mogilnaya. 2003. Results of biomedical investigations of PHB and PHB/PHV fibers. Biochem. Eng. J. 16: 125- 133 
    19. Wong, H. H., R. J. van Wegen, J. Choi, S. Y. Lee, and A. P. J. Middelberg. 1999. Metabolic analysis of poly(3-hydroxybutyrate) production by recombinant Escherichia coli. J. Microbiol. Biotechnol. 9: 593- 603 
    20. Peng, L. and K. Shimizu. 2003. Global metabolic regulation analysis for Escherichia coli K12 based on protein expression by 2-dimensional electrophoresis and enzyme activity measurement. Appl. Microbiol. Biotechnol. 61: 163- 178 
    21. Rhie, H. G. and D. Dennis. 1995. The function of ackA and pfa genes is necessary for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthesis in recombinant pha+ Escherichia coli. Can. J. Microbiol. 41(Suppl. 1): 200- 206 
    22. Sim, S. J., J. D. Snell, S. A. Hogan, J. Stubbe, C. Rha, and A. J. Sinskey. 1997. PHA synthase activity controls the molecular weight and polydispersity of polyhydroxybutyrate in vivo. Nature Biotech. 15: 63- 67 
    23. Steinbiichel, A. and B. Fuchtenbusch. 1998. Bacterial and other biological systems for polyester production. Trends Biotechnol. 16: 419- 427 
    24. Anderson, A. J. and E. A. Dawes. 1990. Occurrence, metabolism, metabolic role, and industrial uses of bacterial polyhydroxyalkanoates. Microbiol. Rev. 54: 450- 472 
    25. Lee, S. Y., Y. K. Lee, and H. N. Chang. 1995. Stimulatory effects of amino acids and oleic acid on poly(3-hydroxybutyric acid) synthesis by recombinant Escherichia coli. J. Ferment. Bioeng. 79: 177-180 
    26. Park, S. J., W. S. Ahn, P. R. Green, and S. Y. Lee. 2001. Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerateco-3-hydroxyhexanoate) by metabolically engineered Escherichia coli strains. Biotechnol. Bioeng. 74: 82- 87 
    27. Valentin, H. E., T. A. Mitsky, D. A. Mahadeo, M. Tran, and K. J. Gruys. 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 
    28. Akhtar S. and C. W. Pouton. 1996. Biosynthetic polyhydroxyalkanoates and their potential in drug delivery. Adv. Drug Deliv. Rev. 18: 133- 162 
    29. Brandl, H., E. J. Knee, R. C. Fuller, R. A. Gross, and R. W. Renz. 1989. Ability of the phototrophic bacterium Rhodospirillum rubum to produce various poly($\beta-hydroxyalkanoates$): Potential sources for biodegradable polyester. Int. J. Biol. Macromol. 11: 49- 55 
    30. Lee, S. Y., K. M. Lee, H. N. Chang, and A. Steinbtichel. 1994. Comparison of Escherichia coli strains for synthesis and accumulation of poly-(3-hydroxybutyric acid), and morphological changes. Biotechnol. Bioeng. 44: 1337-1347 
    31. Kusaka, S., H. Abe, S. Y. Lee, and Y. Doi. 1997. Molecular mass of poly[(R)-3-hydroxybutyric acid] produced in a recombinant Escherichia coli. Appl. Microbiol. Biotechnol. 47: 140-143. 
    32. Lee, S. Y. and J. Choi. 2001. Production of microbial polyester by fermentation of recombinant microorganisms. Adv. Biochem. Eng. Biotechnol. 71: 183- 207 
    33. Slater, S. C., T. Gallahera, and D. Dennis. 1992. Production of poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) in a recombinant Escherichia coli strain. Appl. Environ. Microbiol. 58: 1089- 1094 
    34. Valentin, H. E. and D. Dennis. 1997. Production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in recombinant Escherichia coli grown on glucose. J. Biotechnol. 58: 33-38 
    35. Choi, J. and S. Y. Lee. 1997. Process analysis and economic evaluation for poly(3-hydroxybutyrate) production by fermentation. Bioprocess Eng. 17: 335- 342 
    36. Iwata, T., K. Tsunoda, Y. Aoyagi, S. Kusaka, N. Yoriyuki, and Y. Doi. 2003. Mechanical properties of uniaxially colddrawn films of poly[(R)-3-hydroxybutyrate]. Poly. Degrad. Stabil. 79: 217-224. 
    37. Schubert, P. A. Steinbuchel, and H. G. Schlegel. 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 
    38. Doi, Y. 1990. Microbial Polyesters. VCH, New York, U.S.A 
    39. Lee, S. H., D. H. Oh, W. S. Ahn, Y. Lee, J. Choi, and S. Y. Lee. 2000. Production of poly(3-hydroxybutyrateco-3-hydroxyhexanoate) by high-cell-density cultivation of Aeromonas hydrophila. Biotechnol. Bioeng. 67: 240- 244 
    40. Martin, D. P. and S. F. Williams. 2003. Medical applications of poly-4-hydroxybutyrate: A strong flexible absorbable biomaterial. Biochem. Eng. J. 16: 97- 105 
    41. Aldor, I. and J. D. Keasling. 2001. Metabolic engineering of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) compositi on in recombinant Salmonella enterica serovar typhirnurium. Biotechnol. Bioeng. 76: 108-114 
    42. Kobayashi, G., T. Shiotani, Y. Shima, and Y. Doi. 1994. Biosynthesis and characterization of poly(3-hydroxybutyrateco-3-hydroxyhexanoate) from oils and fats by Aeromonas sp. OL-338 and Aeromonas sp. FA440, pp. 410-416. In Y. Doi, K. Fukuda (eds.), Biodegradable Plastics and Polymers. Elsevier, Amsterdam 
    43. Yun, H. S., D. Y. Kim, C. W. Chung, H. W. Kim, Y. K. Yang, and Y. H. Rhee. 2003. Characterization of a tacky poly(3hydroxyalkanoate) produced by Pseudomonas chlororaphis HS21 from palm kernel oil. J. Microbiol. Biotechnol. 13: 64- 69 
    44. Choi, J. and S. Y. Lee. 1999. High-level production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by fed-batch culture of recombinant Escherichia coli. Appl. Environ. Microbiol. 65: 4363- 4368 
    45. Lee, S. Y. and S. J. Park. 2002. Fermentative production of SCL-PHAs, pp. 263- 290. In Y. Doi and A. Steinbtichel (eds.), Biopolymers vol. 3a. Wiley-VCH, Weinheim 
    46. Valentin, H. E., S. Reiser, and K. J. Gruys. 2000. Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) formation from gammaaminobutyrate and glutamate. Biotechnol. Bioeng. 67: 291-299 
    47. Doi, Y., Y. Janesawa, M. Kunioka, and T. Saito. 1990. Biodegradation of microbial copolyesters: Poly(3- hydroxybutyrate-co-3-hydroxyvalerate) and poly(3- hydroxybutyrate-co-4-hydroxybutyrate ). Macromolecules 23: 26- 31 
    48. Peoples, O. P. and A. J. Sinskey. 1989. $Poly-\beta-hydroxybutyrate$ biosynthesis in Alcaligenes eutrophus H16. Identification and characterization of the PHB polymerase gene (PhbC). J. Biol. Chem. 264: 15298- 15303 
    49. Wang, F. and S. Y. Lee. 1997. Production of poly(3-hydroxybutyrate) by fed-batch culture of filarnentation-suppressed recombinant Escherichia coli. Appl. Environ. Microbiol. 63: 4765- 4769 
    50. Zhao, K., Y. Deng, and G. Q. Chen. 2003. Effects of surface morphology on the biocompatibility of polyhydroxyalkanoates. Biochem. Eng. J. 16: 115- 123 
    51. Adams, J. H., G. Irving, J. H. Koeslag, and J. D. Lochner. 1987. Beta-adrenergic blockade restores glucoses antiketogenic activity after exercise in carbohydrate-depleted athletes. J. Physiol. Lond. 386: 439- 454 
    52. Sendil, D., I. Gursel, D. L. Wise, and V. Hasirci. 1999. Antibiotic release from biodegradable PHBV microparticles. J. Contol. Rel. 59: 207- 217 
    53. Yim, K. S., S. Y. Lee, and H. N. Chang. 1996. Synthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) by recombinant Escherichia coli. Biotechnol. Bioeng. 49: 495- 503 
    54. van Wegen, R. J., S. Y. Lee, and A. P. J. Middelberg. 2001. Metabolic and kinetic analysis of poly(3-hydroxybutyrate) production by recombinant Escherichia coli. Biotechnol. Bioeng. 74: 70- 81 
    55. Williams, S. F., D. P. Martin, D. M. Horowitz, and O. P. Peoples. 1999. PHA application: Addressing the price performance issue I. Tissue engineering. Int. J. Biol. Macromol. 25: 111-121 
    56. Choi, J. and S. Y. Lee. 1999. Factors affecting the economics of polyhydroxyalkanoate production by bacterial fermentation. Appl. Microbiol. Biotechnol. 51: 13- 21 
    57. Doi, Y., S. Kitamura, and H. Abe. 1995. Microbial synthesis and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). Macromolecules 28: 4822- 4828 
    58. Madison, L. L. and G. W. Huisman. 1999. Metabolic engineering of poly(3-hydroxyalkanoates): From DNA to plastic. Microbiol. Mol. Biol. Rev. 63: 21- 53 
    59. Zinn, M., B. Witholt, and T. Egli. 2001. Occurrence, synthesis and medical application of bacterial polyhydroxyalkanoate. Adv. Drug Deliv. Rev. 53: 5- 21 
    60. Kim, D. Y, Y. B. Kim, and Y. H. Rhee. 2002. Cometabolic production of poly(3-hydroxyalkanoates) containing carboncarbon double and triple bonds by Pseudomonas oleovorans. J. Microbiol. Biotechnol. 12: 518- 521 
    61. Yagmurlu, M. E., F. Korkusz, I. Gursel, P. Korkusuz, U. Ors, and V. Hasirci. 1999. Sulbactam-cefoperazone polyhydroxybutyrateco-hydroxyvalerate (PHBV) local antibiotic delivery system: In vivo effectiveness and biocompatibility in the treatment of implant-related experimental osteomyelitis. J. Biomed. Mater. Res. 46: 494- 503 
    62. Hein, S., B. Sohling, G. Gottschalk, and A. Steinbtichel. 1997. Biosynthesis of poly( 4-hydroxybutyric acid) by recombinant strains of Escherichia coli. FEMS Microbiol. Lett. 153: 411-418 
    63. Aoyagi, Y., Y. Doi, and T. Iwata. 2003. Mechanical properties and highly ordered structure of ultra-high-molecular-weight poly[(R)-3-hydroxybutyrate] films: Effect of annealing and two-step drawing. Poly. Degrad. Stabil. 79: 209-216. 
    64. Kato, M., H. J. Bao, C. K. Kang, T. Fukui, and Y. Doi. 1996. Production of a novel copolyester of 3-hydroxybutyric acids and medium-chain-Iength 3-hydroxyalkanoic acids by Pseudomonas sp. 61-3 from sugars. Appl. Microbiol. Biotechnol. 45: 363- 370 
    65. Liu, S. J. and A. Steinbuchel. 2000. A novel genetically engineered pathway for synthesis of poly(hydroxyalkanoic acids) in Escherichia coli. Appl. Environ. Microbiol. 66: 739-743 
    66. Valentin, H. E., G. Zwingmann, A. Schonebaum, and A. Steinbiichel. 1995. Metabolic pathway for biosynthesis of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) from 4-hydroxybutyrate by Alcaligenes eutrophus. Eur. J. Biochem. 227: 43-60 
    67. Zhang, D. M., F. Z. Cui, Z. S. Luo, Y. B. Lin, K. Zhao, and G. Q. Chen. 2000. Wettability improvement of bacterial polyhydroxyalkanoates via ion implatation. Surf. Coat. Technol. 131: 350- 354 
    68. Choi, J., S. Y. Lee, and K. Han. 1998. Cloning of the Alcaligenes latus polyhydroxyalkanoate biosynthesis genes and use of these genes for enhanced production of poly(3-hydroxybutyrate) in Escherichia coli. Appl. Environ. Microbiol. 64: 4897- 4903 
    69. Lee, S. Y., J. Choi, K. Han, and J. Y. Song. 1999. Removal of endotoxin during purification of poly(3-hydroxybutyrate) from gram-negative bacteria. Appl. Environ. Microbiol. 65: 2762- 2764 
    70. Slater, S. C., W. H. Voige, and D. Dennis. 1988. Cloning and expression in Escherichia coli of the Alcaligenes eutrophus H16 $Poly-\beta-hydroxybutyrate$ biosynthetic pathway. J. Bacteriol. 170: 4431- 4436 
  • 이 논문을 인용한 문헌 (4)

    1. 2006. "" Journal of microbiology and biotechnology, 16(12): 1935~1939     
    2. 2006. "" Journal of microbiology and biotechnology, 16(4): 543~549     
    3. 2006. "" Journal of microbiology and biotechnology, 16(6): 901~910     
    4. 2007. "" Journal of microbiology and biotechnology, 17(12): 2018~2026     

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기