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研究生： 李彥儒
Lee, Yen-Ju
論文名稱： 生物製造5-氨基酮戊酸之純化與光動力殺菌應用
Purification and biofabrication of 5-aminolevulinic acid for photodynamic therapy against pathogens
指導教授： 吳意珣
Ng, I-Son
學位類別： 碩士
Master
系所名稱： 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年： 2022
畢業學年度： 110
語文別： 中文
論文頁數： 70
中文關鍵詞： 5-氨基酮戊酸 、離子交換 、層析純化 、光動力殺菌 、微藻 、抗菌
外文關鍵詞： 5-aminolevulinic acid, ion exchange chromatography, antimicrobial, photodynamic therapy, microalgae
相關次數： 點閱：124  下載：6 
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    • 五胺基酮戊酸（5-ALA）是一種參與人體血紅素代謝的非蛋白氨基酸，目前已廣泛應用於農業和醫學領域。 5-ALA可以在驅動下轉化為光敏劑- PpIX，並釋放活性氧 (Reactive oxygen species, ROS)，是為光動力療法 (Photodynamic therapy, PDT)消除病原體或癌細胞的前驅藥。生物合成5-ALA是有效且環保的方法，但培養基中成份複雜較難直接使用，因此後續純化是必要的。在這項研究中，比較鹽酸，醋酸鈉及氨水對5-ALA的脫附效果，最終在pH 9.5，1 M的氨水中得到92%的回收率。隨後，加入活性碳進行脫色去除脫附液中的色素。接著以乙醇和丙酮二步法析出沉澱獲得純度85%的5-ALA結晶。隨後，使用0.25%的純化5-ALA對豪氏變形桿菌 (Proteus hauseri, P. hauseri), 嗜水氣單胞菌 (Aeromonas hydrophila, A. hydrophila), 仙人掌桿菌 (Bacillus cereus, B. cereus) 和金黃色葡萄球菌 (Staphylococcus aureus, S. aureus)進行光動力殺菌 (aPDT)，獲得100%殺菌效率證實了純化5-ALA的抗菌效果。同時，純化後的5-ALA也應用於促進藻類的生長並消除污染藻類培養液的嗜水氣單胞菌，在0.2%的5-ALA幫助下，去除了67.9%的嗜水氣單胞菌並提升了藻類的生長。
    這項研究探討各種不同溶液對5-ALA的脫附效果，利用有機溶劑對5-ALA進行結晶；純化後5-ALA對三種病原菌達成100%殺菌效率，且5-ALA可促進藻類在細菌存在的培養環境不受細菌的影響，除了具有殺菌效率更提高產量，在5-ALA應用上開展了新的方向。

    5-aminolevulinic acid (5-ALA) is a non-proteinogenic amino acid involved in human heme metabolism, which has been broadly applied in the agriculture and medical fields nowadays. 5-ALA can be used for the elimination of pathogens or cancer cells by photodynamic therapy (PDT) owing to its conversion to photosensitizer and release reactive oxygen species (ROS). The biofabrication of 5-ALA is regarded as the most efficient and eco-friendly approach, but the complicated ingredient of medium affects 5-ALA purification, resulting in low recovery and high cost. In this study, HCl, sodium acetate and ammonia were examined to maximize the recovery of 5-ALA from cation exchange chromatography, resulting a 93% recovery in 1 M ammonia at pH 9.5. Afterward, the activated carbon was added for decolorization to further remove other pigments. Different organic solvents were compared for 5-ALA precipitation by 2-steps poor solvent method after being concentrated to 400 g/L by a rotary evaporator. The purify 5-ALA was verified to eliminate Proteus hauseri, Aeromonas hydrophilia (A. hydrophilia), Bacillus cereus and Staphylococcus aureus via anti-microbial PDT with 0.25% 5-ALA to reaching 100% killing rate, respectively. Surprisingly, the growth of microalgae Chlorella sorokiniana was significantly improved with 0.05% 5-ALA to against A. hydrophilia which is a common aquatic pathogen during the cultivation.

    摘要 I Extend Abstract II 誌謝 XI 目錄 XII 表目錄 XV 圖目錄 XVI 縮寫對照表 XVII 第一章 緒論 1 1.1 前言 1 1.2 研究與目的與架構 3 第二章 文獻回顧 5 2.1 五胺基酮戊酸 (5-ALA) 5 2.1.1 5-ALA的介紹 5 2.1.2 5-ALA的化學合成方法 5 2.1.3 5-ALA之生物合成方法 7 2.2 5-ALA純化 8 2.2.1 活性碳脫色 8 2.2.2 離子交換層析 10 2.2.3 析出沉澱 12 2.3 5-ALA之應用 14 2.3.1 在農業上的使用 14 2.3.2 在微藻上的應用 15 2.3.3 光動力治療 16 第三章 實驗材料與方法 19 3.1 實驗藥品 19 3.2 實驗儀器 21 3.3 菌株 22 3.4 溶液配製 23 3.5 實驗方法 25 3.5.1 菌株培養及保存 25 3.5.2 五胺基酮戊酸 (5-ALA)濃度測定 26 3.5.3 利用高效液相色譜（HPLC）進行胺基酸定量分析 28 3.5.3.1 胺基酸定量分析 28 3.5.4 利用離子交換層析和析出沉澱法純化5-ALA 29 3.5.4.1 離子交換樹脂前處理 29 3.5.4.2 吸脫附5-ALA 29 3.5.4.3 活性碳脫色 30 3.5.4.4 旋轉濃縮 30 3.5.4.5 有機溶劑析出結晶 30 3.5.5 5-ALA光動力殺菌 (5-ALA-aPDT) 30 3.5.5.1 光動力殺菌 30 3.5.6 5-ALA在微藻-菌共培養基殺菌實驗 31 3.5.6.1 Chlorella sorokinana (Cs)培養 31 3.5.6.2 5-ALA在微藻-菌共培養基的殺菌實驗 31 第四章 結果與討論 33 4.1 5-ALA離子交換層析的條件優化 33 4.1.1 不同策略放大培養5-ALA發酵液 33 4.1.2 不同溶液對5-ALA的脫附效率 35 4.1.3 以不同液體濃度及pH值優化5-ALA脫附條件 36 4.1.4 樹脂的重複使用測試 38 4.2 5-ALA析出結晶 38 4.2.1 5-ALA脫附液脫色 38 4.2.2 旋轉蒸餾提升5-ALA脫附液濃度 39 4.2.3 不同有機溶劑析出5-ALA結晶 40 4.2.4 二次結晶析出5-ALA 42 4.3 純化5-ALA結晶在光動力殺菌 (aPDT)的應用 43 4.3.1 田口L9直交法優化5-ALA aPDT操作條件 43 4.3.2 以純化5-ALA結晶進行Proteus hauseri殺菌 45 4.3.3 純化後5-ALA結晶對其他病原菌的抗菌效率 47 4.4 5-ALA在微藻中的應用 49 4.4.1 5-ALA於微藻-細菌共培養中的殺菌效率 50 第五章 結論與未來展望 53 5.1 結論 53 5.2 未來展望 55 第六章 參考文獻 56 附錄 66

    1. Akram, N. A., & Ashraf, M. (2013). Regulation in plant stress tolerance by a potential plant growth regulator, 5-aminolevulinic acid. Journal of Plant Growth Regulation, 32(3), 663-679.

    2. Ali, B., Wang, B., Ali, S., Ghani, M. A., Hayat, M. T., Yang, C., et al. (2013). 5-Aminolevulinic acid ameliorates the growth, photosynthetic gas exchange capacity, and ultrastructural changes under cadmium stress in Brassica napus L. Journal of Plant Growth Regulation, 32(3), 604-614.

    3. Ali, S., Rizwan, M., Zaid, A., Arif, M. S., Yasmeen, T., Hussain, A., et al. (2018). 5-Aminolevulinic acid-induced heavy metal stress tolerance and underlying mechanisms in plants. Journal of Plant Growth Regulation, 37(4), 1423-1436.

    4. Archibald, P. A. (1972). A preliminary survey of the edaphic algae of Costa Rica and San Andreas Isle. Soil Science, 113(1), 63-64.

    5. Armbruster, C. E., & Mobley, H. L. (2012). Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis. Nature Reviews Microbiology, 10(11), 743-754.

    6. Averina, N. G., Sherbakov, R. A., Kozel, N. V., Manankina, E. E., Goncharik, R. G., & Shalygo, N. V. (2017). Influence of 5-aminolevulinic acid on the productivity and pigment composition of algae Haematococcus pluvialis. Proceedings of the National Academy of Sciences of Belarus, Biological Series, (4), 21-32.

    7. Becker, W. (2004). 18 microalgae in human and animal nutrition. In Handbook of microalgal culture: biotechnology and applied phycology, 312, Hoboken, NJ, USA: Wiley Online Library.

    8. Bellnier, D. A., Greco, W. R., Loewen, G. M., Nava, H., Oseroff, A. R., & Dougherty, T. J. (2006). Clinical pharmacokinetics of the PDT photosensitizers porfimer sodium (Photofrin), 2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide‐a (Photochlor) and 5‐ALA‐induced protoporphyrin IX. Lasers in Surgery and Medicine: The Official Journal of the American Society for Laser Medicine and Surgery, 38(5), 439-444.

    9. Borowitzka, M. A. (1999). Commercial production of microalgae: ponds, tanks, tubes and fermenters. Journal of Biotechnology, 70(1-3), 313-321.

    10. Brown, B. L., Kardon, J. R., Sauer, R. T., & Baker, T. A. (2018). Structure of the mitochondrial aminolevulinic acid synthase, a key heme biosynthetic enzyme. Structure, 26(4), 580-589.

    11. Bunke, A., Zerbe, O., Schmid, H., Burmeister, G., Merkle, H. P., & Gander, B. (2000). Degradation mechanism and stability of 5‐aminolevulinic acid. Journal of Pharmaceutical Sciences, 89(10), 1335-1341.

    12. Cao, W., Wang, Y., Luo, J., Yin, J., & Wan, Y. (2018). Simultaneous decolorization and deproteinization of α, ω-dodecanedioic acid fermentation broth by integrated ultrafiltration and adsorption treatments. Bioprocess and Biosystems Engineering, 41(9), 1271-1281.

    13. Casas, A., & Batlle, A. (2006). Aminolevulinic acid derivatives and liposome delivery as strategies for improving 5-aminolevulinic acid-mediated photodynamic therapy. Current Medicinal Chemistry, 13(10), 1157-1168.

    14. Chen H, Jiang JG (2011) Toxic effects of chemical pesticides (trichlorfon and dimehypo) on Dunaliella salina. Chemosphere, 84: 664-670.

    15. Chen, J., Keltner, L., Christophersen, J., Zheng, F., Krouse, M., Singhal, A., et al. (2002). New technology for deep light distribution in tissue for phototherapy. The Cancer Journal, 8(2), 154-163.

    16. Chisti, Y. (2007). Biodiesel from microalgae. Biotechnology Advances, 25(3), 294-306.

    17. Choudhary, S., Nouri, K., & Elsaie, M. L. (2009). Photodynamic therapy in dermatology: a review. Lasers in Medical Science, 24(6), 971-980.

    18. De Dardel, F., & Arden, T. V. (2000). Ion exchangers. Ullmann's Encyclopedia of Industrial Chemistry.

    19. Demirbas, A. (2009). Progress and recent trends in biodiesel fuels. Energy Conversion and Management, 50(1), 14-34.

    20. Di Venosa, G., Fukuda, H., Perotti, C., Batlle, A., & Casas, A. (2004). A method for separating ALA from ALA derivatives using ionic exchange extraction. Journal of Photochemistry and Photobiology B: Biology, 75(3), 157-163.

    21. Din, N. A. S., Lim, S. J., Maskat, M. Y., Abd Mutalib, S., & Zaini, N. A. M. (2021). Lactic acid separation and recovery from fermentation broth by ion-exchange resin: A review. Bioresources and Bioprocessing, 8(1), 1-23.

    22. Ding, W., Weng, H., Du, G., Chen, J., & Kang, Z. (2017). 5-Aminolevulinic acid production from inexpensive glucose by engineering the C4 pathway in Escherichia coli. Journal of Industrial Microbiology and Biotechnology, 44(8), 1127-1135.

    23. Dougherty, T. J. (2002). An update on photodynamic therapy applications. Journal of Clinical Laser Medicine & Surgery, 20(1), 3-7.

    24. Elfsson, B., Wallin, I., Eksborg, S., Rudaeus, K., Ros, A. M., & Ehrsson, H. (1999). Stability of 5-aminolevulinic acid in aqueous solution. European Journal of Pharmaceutical Sciences, 7(2), 87-91.

    25. Evans, D. A., & Sidebottom, P. J. (1978). A simple route to α-aminoketones and related derivatives by dianion acylation reactions; an improved preparation of δ-aminolevulinic acid. Journal of the Chemical Society, Chemical Communications, (17), 753-754.

    26. Fehr, M. K., Hornung, R., Degen, A., Schwarz, V. A., Fink, D., Haller, U., et al. (2002). Photodynamic therapy of vulvar and vaginal condyloma and intraepithelial neoplasia using topically applied 5‐aminolevulinic acid. Lasers in Surgery and Medicine: The Official Journal of the American Society for Laser Medicine and Surgery, 30(4), 273-279.

    27. Feng, L., Zhang, Y., Fu, J., Mao, Y., Chen, T., Zhao, X., et al. (2016). Metabolic engineering of Corynebacterium glutamicum for efficient production of 5‐aminolevulinic acid. Biotechnology and Bioengineering, 113(6), 1284-1293.

    28. Fermani, P., Mataloni, G., & Van de Vijver, B. (2007). Soil microalgal communities on an Antarctic active volcano (Deception Island, South Shetlands). Polar Biology, 30(11), 1381-1393.

    29. Fotinos, N., Campo, M. A., Popowycz, F., Gurny, R., & Lange, N. (2006). 5‐Aminolevulinic acid derivatives in photomedicine: Characteristics, application and perspectives. Photochemistry and Photobiology, 82(4), 994-1015.

    30. Fu, W., Lin, J., & Cen, P. (2010). Expression of a hemA gene from Agrobacterium radiobacter in a rare codon optimizing Escherichia coli for improving 5-aminolevulinate production. Applied Biochemistry and Biotechnology, 160(2), 456-466.

    31. Fucke, K., Myz, S. A., Shakhtshneider, T. P., Boldyreva, E. V., & Griesser, U. J. (2012). How good are the crystallisation methods for co-crystals? A comparative study of piroxicam. New Journal of Chemistry, 36(10), 1969-1977.

    32. Gadmar, Ø. B., Moan, J., Scheie, E., Ma, L. W., & Peng, Q. (2002). The stability of 5-aminolevulinic acid in solution. Journal of Photochemistry and Photobiology B: Biology, 67(3), 187-193.

    33. Horie, K., Barón, M., Fox, R. B., He, J., Hess, M., Kahovec, J., et al. (2004). Definitions of terms relating to reactions of polymers and to functional polymeric materials (IUPAC Recommendations 2003). Pure and Applied Chemistry, 76(4), 889-906.

    34. Hotta, Y., Tanaka, T., Takaoka, H., Takeuchi, Y., & Konnai, M. (1997). Promotive effects of 5-aminolevulinic acid on the yield of several crops. Plant Growth Regulation, 22(2), 109-114.

    35. Huang, J., Guo, M., Jin, S., Wu, M., Yang, C., Zhang, G., et al. (2019). Antibacterial photodynamic therapy mediated by 5-aminolevulinic acid on methicillin-resistant Staphylococcus aureus. Photodiagnosis and Photodynamic Therapy, 28, 330-337.

    36. Huddleston, J. R., Zak, J. C., & Jeter, R. M. (2006). Antimicrobial susceptibilities of Aeromonas spp. isolated from environmental sources. Applied and Environmental Microbiology, 72(11), 7036-7042.

    37. Inoue, K. (2017). 5‐Aminolevulinic acid‐mediated photodynamic therapy for bladder cancer. International Journal of Urology, 24(2), 97-101.

    38. Jiao, K., Chang, J., Zeng, X., Ng, I. S., Xiao, Z., Sun, Y., et al. (2017). 5-Aminolevulinic acid promotes arachidonic acid biosynthesis in the red microalga Porphyridium purpureum. Biotechnology for Biofuels, 10(1), 1-10.

    39. Jun, Y. A. N. G., Li, Z. H. U., Weiqi, F. U., Yijun, L. I. N., Jianping, L. I. N., & Peilin, C. E. N. (2013). Improved 5-aminolevulinic acid production with recombinant Escherichia coli by a short-term dissolved oxygen shock in fed-batch fermentation. Chinese Journal of Chemical Engineering, 21(11), 1291-1295.

    40. Juzeniene, A., Juzenas, P., Iani, V., & Moan, J. (2002). Topical Application of 5‐Aminolevulinic Acid and its Methylester, Hexylester and Octylester Derivatives: Considerations for Dosimetry in Mouse Skin Model. Photochemistry and Photobiology, 76(3), 329-334.

    41. Kaketani, K., & Nakajima, M. (2021). Safety, tolerability, and efficacy of 5-aminolevulinic acid phosphate, an inducer of heme oxygenase 1, in combination with sodium ferrous citrate for the treatment of COVID-19 patients. The Open COVID Journal, 1(1).

    42. Kalka, K., Merk, H., & Mukhtar, H. (2000). Photodynamic therapy in dermatology. Journal of the American Academy of Dermatology, 42(3), 389-413.

    43. Kamp, H., Tietz, H. J., Lutz, M., Piazena, H., Sowyrda, P., Lademann, J., et al. (2005). Antifungal effect of 5‐aminolevulinic acid PDT in Trichophyton rubrum. Mycoses, 48(2), 101-107.

    44. Kang, Z., Ding, W., Gong, X., Liu, Q., Du, G., & Chen, J. (2017). Recent advances in production of 5-aminolevulinic acid using biological strategies. World Journal of Microbiology and Biotechnology, 33(11), 1-7.

    45. Khan, S. A., Hussain, M. Z., Prasad, S., & Banerjee, U. C. (2009). Prospects of biodiesel production from microalgae in India. Renewable and Sustainable Energy Reviews, 13(9), 2361-2372.

    46. Konsowa, A. H., Ossman, M. E., Chen, Y., & Crittenden, J. C. (2010). Decolorization of industrial wastewater by ozonation followed by adsorption on activated carbon. Journal of Hazardous Materials, 176(1-3), 181-185.

    47. Korkmaz, A., Korkmaz, Y., & Demirkıran, A. R. (2010). Enhancing chilling stress tolerance of pepper seedlings by exogenous application of 5-aminolevulinic acid. Environmental and Experimental Botany, 67(3), 495-501.

    48. Lee, J. A., Ahn, J. H., Kim, I., Li, S., & Lee, S. Y. (2019). Separation and purification of three, four, and five carbon diamines from fermentation broth. Chemical Engineering Science, 196, 324-332.

    49. Lin, J. Y., Xue, C., Tan, S. I., & Ng, I. S. (2021). Pyridoxal kinase PdxY mediated carbon dioxide assimilation to enhance the biomass in Chlamydomonas reinhardtii CC-400. Bioresource Technology, 322, 124530.

    50. Ling, X. U., Islam, F., ZHANG, W. F., Ghani, M. A., & Ali, B. (2018). 5-Aminolevulinic acid alleviates herbicide-induced physiological and ultrastructural changes in Brassica napus. Journal of integrative agriculture, 17(3), 579-592.

    51. Lozano-Castelló, D., Cazorla-Amorós, D., Linares-Solano, A., & Quinn, D. F. (2002). Activated carbon monoliths for methane storage: influence of binder. Carbon, 40(15), 2817-2825.

    52. Lyu, X., Lyu, Y., Yu, H., Chen, W., Ye, L., & Yang, R. (2022). Biotechnological advances for improving natural pigment production: a state-of-the-art review. Bioresources and Bioprocessing, 9(1), 1-38.

    53. MacENTEE, F. J., Bold, H. C., & Archibald, P. A. (1977). Notes on some edaphic algae of the South Pacific and Malaysian areas, with special reference to Pseudotetraedron polymorphum. Soil Science, 124(3), 161-166.

    54. Mascal, M., & Dutta, S. (2011). Synthesis of the natural herbicide δ-aminolevulinic acid from cellulose-derived 5-(chloromethyl) furfural. Green Chemistry, 13(1), 40-41.

    55. Miscevic, D., Mao, J. Y., Kefale, T., Abedi, D., Moo‐Young, M., & Perry Chou, C. (2021). Strain engineering for high‐level 5‐aminolevulinic acid production in Escherichia coli. Biotechnology and Bioengineering, 118(1), 30-42.

    56. Moreira, M. J. A., & Gando-Ferreira, L. M. (2012). Separation of phenylalanine and tyrosine by ion-exchange using a strong-base anionic resin. I. Breakthrough curves analysis. Biochemical Engineering Journal, 67, 231-240.

    57. Okada, H., Tanaka, T., & Nomura, T. (2012). U.S. Patent No. 8,148,574. Washington, DC: U.S. Patent and Trademark Office.

    58. Omwene, P. I., Yagcioglu, M., Sarihan, Z. B. O., Karagunduz, A., & Keskinler, B. (2020). Recovery of succinic acid from whey fermentation broth by reactive extraction coupled with multistage processes. Journal of Environmental Chemical Engineering, 8(5), 104216.

    59. Park, S. J., Kim, E. Y., Noh, W., Park, H. M., Oh, Y. H., Lee, S. H., et al. (2013). Metabolic engineering of Escherichia coli for the production of 5-aminovalerate and glutarate as C5 platform chemicals. Metabolic Engineering, 16, 42-47.

    60. Patrickios, C. S., & Yamasaki, E. N. (1995). Polypeptide amino acid composition and isoelectric point ii. comparison between experiment and theory. Analytical Biochemistry, 231(1), 82-91.

    61. Pérez-Laguna, V., García-Luque, I., Ballesta, S., Pérez-Artiaga, L., Lampaya-Pérez, V., Samper, S., et al. (2018). Antimicrobial photodynamic activity of Rose Bengal, alone or in combination with Gentamicin, against planktonic and biofilm Staphylococcus aureus. Photodiagnosis and Photodynamic Therapy, 21, 211-216.

    62. Piotrowska, M., & Popowska, M. (2014). The prevalence of antibiotic resistance genes among Aeromonas species in aquatic environments. Annals of Microbiology, 64(3), 921-934.

    63. Ray, J. G., & Thomas, B. T. (2012). Fertility characteristics of oxic dystrustepts under natural forest, rubber, and teak plantations in different seasons, Kerala, South India. Communications in Soil Science and Plant Analysis, 43(17), 2247-2261.

    64. Rebeiz, C. A., Amindari, S., Reddy, K. N., Nandihalli, U. B., Moubarak, M. B., & Velu, J. A. (1994). δ-Aminolevulinic acid based herbicides and tetrapyrrole biosynthesis modulators. Porphyric Pesticides, 4, 48-64.

    65. Rebeiz, C. A., Juvik, J. A., Rebeiz, C. C., Bouton, C. E., & Gut, L. J. (1990). Porphyric insecticides: 2. 1, 10-Phenanthroline, a potent porphyric insecticide modulator. Pesticide Biochemistry and Physiology, 36(2), 201-207.

    66. Ren, J., Zhou, L., Wang, C., Lin, C., Li, Z., & Zeng, A. P. (2018). An unnatural pathway for efficient 5-aminolevulinic acid biosynthesis with glycine from glyoxylate based on retrobiosynthetic design. ACS Synthetic Biology, 7(12), 2750-2757.

    67. SHikh Bardsiri, H., & SHekibaei, M. R. (2013). Plasmid pattern of biofilm producing Proteus mirabilis and Proteus vulgaris among clinical isolates in Kerman university hospitals during 2011-2012. Journal of Kerman University of Medical Sciences, 20(2), 146-157.

    68. Song, D., Fu, J., & Shi, D. (2008). Exploitation of oil-bearing microalgae for biodiesel. Chinese Journal of Biotechnology, 24(3), 341-348.

    69. Soo, Y., Chada, N., Beckner, M., Romanos, J., Burress, J., & Pfeifer, P. (2013). Adsorbed methane film properties in nanoporous carbon monoliths. In APS March Meeting Abstracts, 2013, 38-001.

    70. Spolaore, P., Joannis-Cassan, C., Duran, E., & Isambert, A. (2006). Commercial applications of microalgae. Journal of Bioscience and Bioengineering, 101(2), 87-96.

    71. Switka-Wieclawska, I., Kecik, T., Kwasny, M., & Graczyk, A. (2003). Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea. In Laser Technology VII: Applications of Lasers, 5229, 82-86.

    72. Szeimies, R. M., Landthaler, M., & Karrer, S. (2002). Non-oncologic indications for ALA-PDT. Journal of Dermatological Treatment, 13, s13-s18.

    73. Tachiya, N. (2012). U.S. Patent No. 8,158,821. Washington, DC: U.S. Patent and Trademark Office.

    74. Tangprasittipap, A., & Prasertsan, P. (2002). 5-aminolevulinic acid from photosynthetic bacteria and its applications. Songklanakarin Journal of Science and Technology, 24(4), 717-725.

    75. Tredici, M. R. (2010). Photobiology of microalgae mass cultures: understanding the tools for the next green revolution. Biofuels, 1(1), 143-162.

    76. Tripetch, P., Srzednicki, G., & Borompichaichartkul, C. (2012). Separation process of 5-aminolevulinic acid from Rhodobacter spaeroides for increasing value of agricultural product by ion exchange chromatography. In II Asia Pacific Symposium on Postharvest Research Education and Extension: APS2012 1011 (pp. 265-271).

    77. Wang, H., Zhang, W., Chen, L., Wang, J., & Liu, T. (2013). The contamination and control of biological pollutants in mass cultivation of microalgae. Bioresource Technology, 128, 745-750.

    78. Wang, J., & Scott, A. I. (1997). An efficient synthesis of δ-aminolevulinic acid (ALA) and its isotopomers. Tetrahedron Letters, 38(5), 739-740.

    79. Wang, J., Zhang, J., Li, J., Dawuda, M. M., Ali, B., Wu, Y., & Xie, J. (2021). Exogenous application of 5-aminolevulinic acid promotes coloration and improves the quality of tomato fruit by regulating carotenoid metabolism. Frontiers in Plant Science, 1022.

    80. Wang, L. J., Jiang, W. B., & Huang, B. J. (2004). Promotion of 5‐aminolevulinic acid on photosynthesis of melon (Cucumis melo) seedlings under low light and chilling stress conditions. Physiologia Plantarum, 121(2), 258-264.

    81. Xie, L., Wang, Z. H., Cheng, X. H., Gao, J. J., Zhang, Z. P., & Wang, L. J. (2013). 5-Aminolevulinic acid promotes anthocyanin accumulation in Fuji apples. Plant Growth Regulation, 69(3), 295-303.

    82. Yang, M. L., Kun, Y. I. N., Guo, Y. P., & Zhang, J. Z. (2011). A Photosensitivity Insecticide, 5-Aminolevulinic Acid, Exerts Effective Toxicity to Oxya chinensis (Orthoptera: Acridoidea). Agricultural Sciences in China, 10(7), 1056-1063.

    83. Yang, P., Liu, W., Cheng, X., Wang, J., Wang, Q., & Qi, Q. (2016). A new strategy for production of 5-aminolevulinic acid in recombinant Corynebacterium glutamicum with high yield. Applied and Environmental Microbiology, 82(9), 2709-2717.

    84. Yang, X., Li, W., Palasuberniam, P., Myers, K. A., Wang, C., & Chen, B. (2015). Effects of silencing heme biosynthesis enzymes on 5‐aminolevulinic acid‐mediated protoporphyrin IX fluorescence and photodynamic therapy. Photochemistry and Photobiology, 91(4), 923-930.

    85. Yi, Y. C., Shih, I. T., Yu, T. H., Lee, Y. J., & Ng, I. S. (2021). Challenges and opportunities of bioprocessing 5-aminolevulinic acid using genetic and metabolic engineering: a critical review. Bioresources and Bioprocessing, 8(1), 1-18.

    86. Yi, Y. C., Xue, C., & Ng, I. S. (2021). Low-Carbon-Footprint Production of High-End 5-Aminolevulinic Acid via Integrative Strain Engineering and RuBisCo-Equipped Escherichia coli. ACS Sustainable Chemistry & Engineering, 9(46), 15623-15633.

    87. Yu, T. H., Tan, S. I., Yi, Y. C., Xue, C., Ting, W. W., Chang, J. J., et al. (2022). New insight into the codon usage and medium optimization toward stable and high-level 5-aminolevulinic acid production in Escherichia coli. Biochemical Engineering Journal, 177, 108259.

    88. Yu, X., Jin, H., Liu, W., Wang, Q., & Qi, Q. (2015). Engineering Corynebacterium glutamicum to produce 5-aminolevulinic acid from glucose. Microbial Cell Factories, 14(1), 1-10.

    89. Zhang, J., Weng, H., Ding, W., & Kang, Z. (2017). N-terminal engineering of glutamyl-tRNA reductase with positive charge arginine to increase 5-aminolevulinic acid biosynthesis. Bioengineered, 8(4), 424-427.

    90. Zhang, Z. J., Li, H. Z., Zhou, W. J., Takeuchi, Y., & Yoneyama, K. (2006). Effect of 5-aminolevulinic acid on development and salt tolerance of potato (Solanum tuberosum L.) microtubers in vitro. Plant Growth Regulation, 49(1), 27-34.

    91. Zhao, M., Li, G., Deng, Y. (2018). Engineering Escherichia coli for glutarate production as the C5 platform backbone. Applied and Environmental Microbiology, 84(16), e00814-18.

    92. Zhu Z, Jiang J, & Fa Y. (2020) Overcoming the biological contamination in microalgae and cyanobacteria mass cultivations for photosynthetic biofuel production. Molecules 25: 5220.

    93. Zhu, S., Song, Y., Pei, J., Xue, F., Cui, X., Xiong, X., et al. (2021). The application of photodynamic inactivation to microorganisms in food. Food Chemistry: X, 12, 100150.

    94. 王丽君, 闫思翰, 杨套伟, 徐美娟, 张显, 邵明龙 等人 (2021). 代谢改造重组谷氨酸棒杆菌C4途径高效合成5-氨基乙酰丙酸.

    95. 立谷尚久 (2007). 5-氨基乙酰丙酸磷酸盐的新型晶体及其制备方法. CN101472879B, 2007.

    96. 立谷尚久,西川诚司,肥后麻衣,田中彻,石塚昌宏& 冈田秀树 (2005). 5－氨基乙酰丙酸盐、其制备方法及其用途. CN1942430A, 2005.

    97. 江燕斌,马建,杨建,周新荣& 朱义福 (2011). 一种有机溶剂沉淀分离初步提纯谷胱甘肽发酵液的方法. CN102286069A, 2011.

    98. 林建平, 张露露, 朱力& 岑沛霖. (2009). 一种5-氨基乙酰丙酸盐酸盐的结晶方法. CN101624350B, 2009.

    99. 陳進庭, 林郁欣 (2006). 光動力醫學的原理及其應用發展.

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