Thách thức và cơ hội trong quy trình sinh học sản xuất 5-aminolevulinic acid bằng cách sử dụng kỹ thuật di truyền và chuyển hóa: một bài tổng quan phê phán

Bioresources and Bioprocessing - Tập 8 - Trang 1-18 - 2021
Ying-Chen Yi1, I-Tai Shih1, Tzu-Hsuan Yu1, Yen-Ju Lee1, I-Son Ng1
1Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan

Tóm tắt

Axít 5-aminolevulinic (5-ALA), một axít amin năm carbon không phải protein, đã nhận được sự chú ý đáng kể trong y học do việc được Cục Quản lý Thực phẩm và Dược phẩm Hoa Kỳ (FDA) phê duyệt cho việc chẩn đoán và điều trị ung thư dưới dạng liệu pháp quang động. Do việc tổng hợp hóa học 5-ALA có hiệu suất thấp, quy trình phức tạp và chi phí cao, nên sinh tổng hợp 5-ALA thông qua con đường C4 (còn gọi là con đường Shemin) và con đường C5 liên quan đến sự sinh tổng hợp heme trong vi sinh vật cho nhiều lợi thế hơn. Trong con đường C4, 5-ALA được hình thành từ phản ứng ngưng tụ của succinyl-CoA và glycine nhờ vào enzyme tổng hợp axít 5-aminolevulinic (ALAS) với pyridoxal phosphate (PLP) đóng vai trò là đồng yếu tố trong quá trình chuyển hóa sinh học một bước. Con đường C5 liên quan đến ba enzyme bao gồm glutamyl-tRNA synthetase (GltX), glutamyl-tRNA reductase (HemA), và glutamate-1-semialdehyde aminotransferase (HemL) từ α-ketoglutarate trong chu trình TCA thành 5-ALA và heme. Trong bài tổng quan này, chúng tôi mô tả những kết quả gần đây về sản xuất 5-ALA từ các gen và vi sinh vật khác nhau thông qua các phương pháp kỹ thuật di truyền và chuyển hóa. Sự điều chỉnh của các khung vi sinh vật khác nhau được tinh chỉnh bằng cách áp dụng sinh học tổng hợp và cuối cùng tăng cường sản xuất 5-ALA. Quá trình tinh chế, những thách thức và cơ hội của 5-ALA cho các ứng dụng công nghiệp cũng được tóm tắt.

Từ khóa

#5-aminolevulinic acid #sinh tổng hợp #kỹ thuật di truyền #chuyển hóa #quy trình sinh học #heme #ứng dụng công nghiệp

Tài liệu tham khảo

Aiguo Z, Meizhi Z (2019) Production of 5-aminolevulinic acid from glutamate by overexpressing HemA1 and pgr7 from Arabidopsis thaliana in Escherichia coli. World J Microbiol Biotechnol 35:175 Amos-Tautua BM, Songca SP, Oluwafemi OS (2019) Application of porphyrins in antibacterial photodynamic therapy. Molecules 24:2456 Angov E (2011) Codon usage: nature’s roadmap to expression and folding of proteins. Biotechnol J 6:650–659 Anné J, Vrancken K, Van Mellaert L, Van Impe J, Bernaerts K (2014) Protein secretion biotechnology in Gram-positive bacteria with special emphasis on Streptomyces lividans. Biochim Biophys Acta Mol Cell Res 1843:1750–1761 Beale SI (1970) The biosynthesis of δ-aminolevulinic acid in Chlorella. Plant Physiol 45:504–506 Bunke A, Zerbe O, Schmid H, Burmeister G, Merkle HP, Gander B (2000) Degradation mechanism and stability of 5-aminolevulinic acid. J Pharm Sci 89:1335–1341 Burgess-Brown NA, Sharma S, Sobott F, Loenarz C, Oppermann U, Gileadi O (2008) Codon optimization can improve expression of human genes in Escherichia coli: a multi-gene study. Protein Expr Purif 59:94–102 Chen J, Wang Y, Guo X, Rao D, Zhou W, Zheng P et al (2020) Efficient bioproduction of 5-aminolevulinic acid, a promising biostimulant and nutrient, from renewable bioresources by engineered Corynebacterium glutamicum. Biotechnol Biofuels 13:1–13 Cheng F, Wang J, Song Z, Cheng JE, Zhang D, Liu Y (2017) Nematicidal effects of 5-aminolevulinic acid on plant-parasitic nematodes. J Nematol 49:295 Cho SW, Yim J, Seo SW (2020) Engineering tools for the development of recombinant lactic acid bacteria. Biotechnol J 15:e1900344 Choi C, Hong BS, Sung HC, Lee HS, Kim JH (1999) Optimization of extracellular 5-aminolevulinic acid production from Escherichia coli transformed with ALA synthase gene of Bradyrhizobium japonicum. Biotechnol Lett 21:551–554 Choi HP, Lee YM, Yun CW, Sung HC (2008) Extracellular 5-aminolevulinic acid production by Escherichia coli containing the Rhodopseudomonas palustris KUGB306 hemA gene. J Microbiol Biotechnol 18:1136–1140 Chung SY, Seo KH, Rhee JI (2005) Influence of culture conditions on the production of extra-cellular 5-aminolevulinic acid (ALA) by recombinant E. coli. Process Biochem 40:385–394 Cui Z, Jiang Z, Zhang J, Zheng H, Jiang X, Gong K et al (2019) Stable and efficient biosynthesis of 5-aminolevulinic acid using plasmid-free Escherichia coli. J Agric Food Chem 67:1478–1483 de Marco A, Deuerling E, Mogk A, Tomoyasu T, Bukau B (2007) Chaperone-based procedure to increase yields of soluble recombinant proteins produced in E. coli. BMC Biotechnol 7:32 Diesveld R, Tietze N, Fürst O, Reth A, Bathe B, Sahm H, Eggeling L (2009) Activity of exporters of Escherichia coli in Corynebacterium glutamicum, and their use to increase L-threonine production. J Mol Microbiol Biotechnol 16:198–207 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. J Ind Microbiol Biotechnol 44:1127–1135 Dolmans DE, Fukumura D, Jain RK (2003) Photodynamic therapy for cancer. Nat Rev Cancer 3:380–387 Effendi SSW, Tan SI, Chang CH, Chen CY, Chang JS, Ng IS (2020) Development and fabrication of disease resistance protein in recombinant Escherichia coli. Bioresour Bioprocess 7:1–10 Erskine PT, Norton E, Cooper JB, Lambert R, Coker A, Lewis G et al (1999) X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 Å resolution. Biochemistry 38:4266–4276 Farid M, Ali S, Rizwan M, Ali Q, Saeed R, Nasir T et al (2018) Phyto-management of chromium contaminated soils through sunflower under exogenously applied 5-aminolevulinic acid. Ecotoxicol Environ Saf 151:255–265 Feng L, Zhang Y, Fu J, Mao Y, Chen T, Zhao X, Wang Z (2016) Metabolic engineering of Corynebacterium glutamicum for efficient production of 5-aminolevulinic acid. Biotechnol Bioeng 113:1284–1293 Fu W, Lin J, Cen P (2007) 5-Aminolevulinate production with recombinant Escherichia coli using a rare codon optimizer host strain. Appl Microbiol Biotechnol 75:777–782 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. Appl Biochem Biotechnol 160:456–466 Fuglsang A (2003) Codon optimizer: a freeware tool for codon optimization. Protein Expr Purif 31:247–249 Gadmar ØB, Moan J, Scheie E, Ma LW, Peng Q (2002) The stability of 5-aminolevulinic acid in solution. J Photochem Photobiol B 67:187–193 Hara KY, Saito M, Kato H, Morikawa K, Kikukawa H, Nomura H et al (2019) 5-Aminolevulinic acid fermentation using engineered Saccharomyces cerevisiae. Microb Cell Fact 18:1–8 Hayer-Hartl M, Bracher A, Hartl FU (2016) The GroEL–GroES chaperonin machine: a nano-cage for protein folding. Trends Biochem Sci 41:62–76 Hoppe M, Brün B, Larsson MP, Moraeus L, Hulthén L (2013) Heme iron-based dietary intervention for improvement of iron status in young women. Nutr 29:89–95 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 Regul 22:109–114 Huang DD, Wang WY (1986) Chlorophyll biosynthesis in Chlamydomonas starts with the formation of glutamyl-tRNA. Int J Biol Chem 261:13451–13455 Jahn D, Verkamp E, So D (1992) Glutamyl-transfer RNA:a precursor of heme and chlorophyll biosynthesis. Trends Biochem Sci 17:215–218 Jones JA, Toparlak ÖD, Koffas MA (2015) Metabolic pathway balancing and its role in the production of biofuels and chemicals. Curr Opin Biotechnol 33:52–59 Jung S, Yang K, Lee DE, Back K (2004) Expression of Bradyrhizobium japonicum 5-aminolevulinic acid synthase induces severe photodynamic damage in transgenic rice. Plant Sci 167:789–795 Kane JF (1995) Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli. Curr Opin Biotechnol 6:494–500 Kang DK, Kim SS, Chi WJ, Hong SK, Kim HK, Kim HU (2004) Cloning and expression of the Rhodobacter capsulatus hemA gene in E. coli for the production of 5-aminolevulinic acid. J Microbiol Biotechnol 14:1327–1332 Kang Z, Wang Y, Gu P, Wang Q, Qi Q (2011a) Engineering Escherichia coli for efficient production of 5-aminolevulinic acid from glucose. Metab Eng 13:492–498 Kang Z, Wang Y, Wang Q, Qi Q (2011b) Metabolic engineering to improve 5-aminolevulinic acid production. Bioeng Bugs 2:342–345 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 J Microbiol Biotechnol 33:200 Kennedy J, Pottier RH, Pross DC (1990) Photodynamic therapy with endogenous protoporphyrin: IX: basic principles and present clinical experience. J Photochem Photobiol B 6:143–148 Ko YJ, You SK, Kim M, Lee E, Shin SK, Park HM et al (2019) Enhanced production of 5-aminolevulinic acid via flux redistribution of tca cycle toward L-glutamate in Corynebacterium glutamicum. Biotechnol Bioprocess Eng 24:915–923 Krieg RC, Messmann H, Rauch J, Seeger S, Knuechel R (2002) Metabolic characterization of tumor cell–specific protoporphyrin IX accumulation after exposure to 5-aminolevulinic acid in human colonic cells. Photochem Photobiol 76:518–525 Kwon SJ, De Boer AL, Petri R, Schmidt-Dannert C (2003) High-level production of porphyrins in metabolically engineered Escherichia coli: systematic extension of a pathway assembled from overexpressed genes involved in heme biosynthesis. Appl Environ Microbiol 69:4875–4883 Li JM, Russell CS, Cosloy SD (1989) Cloning and structure of the hemA gene of Escherichia coli K-12. Gene 82:209–217 Li F, Wang Y, Gong K, Wang Q, Liang Q, Qi Q (2014) Constitutive expression of RyhB regulates the heme biosynthesis pathway and increases the 5-aminolevulinic acid accumulation in Escherichia coli. FEMS Microbiol Lett 350:209–215 Li T, Guo YY, Qiao GQ, Chen GQ (2016) Microbial synthesis of 5-aminolevulinic acid and its coproduction with polyhydroxybutyrate. ACS Synth Biol 5:1264–1274 Lin J, Fu W, Cen P (2009) Characterization of 5-aminolevulinate synthase from Agrobacterium radiobacter, screening new inhibitors for 5-aminolevulinate dehydratase from Escherichia coli and their potential use for high 5-aminolevulinate production. Bioresour Technol 100:2293–2297 Lin J, Lou J, Cen P (2014) Crystallization method of 5-aminolevulinic acid phosphate. CN103265444B, 5 November 2014. Liu D, Wu L, Naeem MS, Liu H, Deng X, Xu L et al (2013) 5-Aminolevulinic acid enhances photosynthetic gas exchange, chlorophyll fluorescence and antioxidant system in oilseed rape under drought stress. Acta Physiol Plant 35:2747–2759 Liu S, Zhang G, Li X, Zhang J (2014) Microbial production and applications of 5-aminolevulinic acid. Appl Microbiol Biotechnol 98:7349–7357 Liu S, Li X, Zhang G, Zhang J (2015) Optimization of influencing factors on biomass accumulation and 5-aminolevulinic acid (ALA) yield in Rhodobacter sphaeroides wastewater treatment. J Microbiol Biotechnol 25:1920–1927 Liu S, Zhang G, Li J, Li X, Zhang J (2016) Effects of metal ions on biomass and 5-aminolevulinic acid production in Rhodopseudomonas palustris wastewater treatment. Water Sci Technol 73:382–388 Liu S, Zheng Z, Tie J, Kang J, Zhang G, Zhang J (2018) Impacts of Fe2+ on 5-aminolevulinic acid (ALA) biosynthesis of Rhodobacter sphaeroides in wastewater treatment by regulating nif gene expression. Res J Environ Sci 70:11–19 Liu J, Ye Z, Wu H, Liu J, Gong Y (2020) Overexpression of hemA and hemL in Bacillus subtilis promotes overexpression of 5-aminolevulinic acid. Indian J Anim Res 54. Lou JW, Zhu L, Wu MB, Yang LR, Lin JP, Cen PL (2014) High-level soluble expression of the hemA gene from Rhodobacter capsulatus and comparative study of its enzymatic properties. J Zhejiang Univ Sci B 15:491–499 Lüer C, Schauer S, Möbius K, Schulze J, Schubert WD, Heinz DW et al (2005) Complex formation between glutamyl-tRNA reductase and glutamate-1-semialdehyde 2, 1-aminomutase in Escherichia coli during the initial reactions of porphyrin biosynthesis. Int J Biol Chem 280:18568–18572 Malik Z, Lugaci H (1987) Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins. Br J Cancer 56:589 Mao Y, Chen Z, Lu L, Jin B, Ma H, Pan Y, Chen T (2020) Efficient solid-state fermentation for the production of 5-aminolevulinic acid enriched feed using recombinant Saccharomyces cerevisiae. J Biotechnol 322:29–32 Martens JH, Barg H, Warren MA, Jahn D (2002) Microbial production of vitamin B12. Appl Microbiol Biotechnol 58:275–285 Mayfield JA, Dehner CA, DuBois JL (2011) Recent advances in bacterial heme protein biochemistry. Curr Opin Chem Biol 15:260–266 McNicholas PM, Javor G, Darie S, Gunsalus RP (1997) Expression of the heme biosynthetic pathway genes hemCD, hemH, hemM and hemA of Escherichia coli. FEMS Microbiol Lett 146:143–148 Meierhofer C, Silic K, Urban MV, Tanew A, Radakovic S (2021) The impact of occlusive vs non-occlusive application of 5-aminolevulinic acid (BF-200 ALA) on the efficacy and tolerability of photodynamic therapy for actinic keratosis on the scalp and face: a prospective within-patient comparison trial. Photodermatol Photoimmunol Photomed 37:56–62 Meng Q, Zhang Y, Ma C, Ma H, Zhao X, Chen T (2015) Purification and functional characterization of thermostable 5-aminolevulinic acid synthases. Biotechnol Lett 37:2247–2253 Menzella HG (2011) Comparison of two codon optimization strategies to enhance recombinant protein production in Escherichia coli. Microb Cell Fact 10:15 Miscevic D, Mao JY, Kefale T, Abedi D, Moo-Young M, Chou CP (2020) Strain engineering for high-level 5-aminolevulinic acid production in Escherichia coli. Biotechnol Bioeng. https://doi.org/10.1002/bit.27547 Naeem MS, Warusawitharana H, Liu H, Liu D, Ahmad R, Waraich EA et al (2012) 5-Aminolevulinic acid alleviates the salinity-induced changes in Brassica napus as revealed by the ultrastructural study of chloroplast. Plant Physiol Biochem 57:84–92 Nakakuki M, Yamauchi K, Hayashi N, Kikuchi G (1980) Purification and some properties of delta-aminolevulinate synthase from the rat liver cytosol fraction and immunochemical identity of the cytosolic enzyme and the mitochondrial enzyme. J Biol Chem 255:1738–1745 Nandi DL, Baker-Cohen KF, Shemin D (1968) δ-Aminolevulinic acid dehydratase of Rhodopseudomonas spheroides I. Isolation and properties. Int J Biol Chem 243:1224–1230 Noh MH, Lim HG, Park S, Seo SW, Jung GY (2017) Precise flux redistribution to glyoxylate cycle for 5-aminolevulinic acid production in Escherichia coli. Metab Eng 43:1–8 Nordmann NJ, Michael AP (2020) 5-Aminolevulinic acid radiodynamic therapy for treatment of high-grade gliomas: systematic review. Clin Neurol Neurosurg. 201:106430 Okada H, Tanaka T, Nomura T (2016) Process for producing 5-aminolevulinic acid hydrochloride. EP1927586B1, 27 April 2016. Ong PY, Lee CT, Sarmidi MR, Awad HM, Chua LS, Razali F (2013) Production of extracellular 5-aminolevulinic acid by Rhodopseudomonas palustris in solid-state fermentation. Developments in sustainable chemical and bioprocess technology. Springer, Boston, pp 173–179 Peng Q, Warloe T, Berg K, Moan J, Kongshaug M, Giercksky KE, Nesland JM (1997a) 5-Aminolevulinic acid-based photodynamic therapy: clinical research and future challenges. Cancer 79:2282–2308 Peng Q, Berg K, Moan J, Kongshaug M, Nesland JM (1997b) 5-Aminolevulinic acid-based photodynamic therapy: principles and experimental research. Photochem Photobiol 65:235–251 Ramzi AB, Hyeon JE, Kim SW, Park C, Han SO (2015) 5-Aminolevulinic acid production in engineered Corynebacterium glutamicum via C5 biosynthesis pathway. Enzyme Microb Technol 81:1–7 Sasaki K, Watanabe M, Tanaka T (2002) Biosynthesis, biotechnological production and applications of 5-aminolevulinic acid. Appl Microbiol Biotechnol 58:23–29 Sasikala C, Ramana CV, Rao PR (1994) 5-aminolevulinic acid: a potential herbicide/insecticide from microorganisms. Biotechnol Prog 10:451–459 Sato K, Ishida K, Mutsushika O, Shimizu S (1985) Purification and some properties of δ-aminolevulinic acid synthases from Protaminobacter ruber and Rhodopseudomonas spheroides. Agric Biol Chem 49:3415–3421 Schauer S, Chaturvedi S, Randau L, Moser J, Kitabatake M, Lorenz S et al (2002) Escherichia coli glutamyl-tRNA reductase trapping the thioester intermediate. Int J Biol Chem 277:48657–48663 Schneegurt MA, Beale SI (1988) Characterization of the RNA required for biosynthesis of δ-aminolevulinic acid from glutamate: purification by anticodon-based affinity chromatography and determination that the UUC glutamate anticodon is a general requirement for function in ALA biosynthesis. Plant Physiol 86:497–504 Shih IT, Yi YC, Ng IS (2021) Plasmid-Free System and modular design for efficient 5-aminolevulinic acid production by engineered Escherichia coli. Appl Biochem Biotechnol 193:1–14 Shinoda Y, Kato D, Ando R, Endo H, Takahashi T, Tsuneoka Y, Fujiwara Y (2021) Systematic review and meta-analysis of in vitro anti-human cancer experiments investigating the use of 5-aminolevulinic acid (5-ALA) for photodynamic therapy. Pharmaceuticals 14:229 Sørensen HP, Mortensen KK (2005) Advanced genetic strategies for recombinant protein expression in Escherichia coli. J Biotechnol 115:113–128 Stojanovski BM, Ferreira GC (2015) Asn-150 of murine erythroid 5-aminolevulinate synthase modulates the catalytic balance between the rates of the reversible reaction. J Biol Chem 290:30750–30761 Stojanovski BM, Hunter GA, Jahn M, Jahn D, Ferreira GC (2014) Unstable reaction intermediates and hysteresis during the catalytic cycle of 5-aminolevulinate synthase implications from using pseudo and alternate substrates and a promiscuous enzyme variant. J Biol Chem 289:22915–22925 Su T, Guo Q, Zheng Y, Liang Q, Wang Q, Qi Q (2019) Fine-tuning of hemB using CRISPRi for increasing 5-aminolevulinic acid production in Escherichia coli. Front Microbiol 10:1731 Tan SI, Ng IS (2021) Stepwise optimization of genetic RuBisCO-equipped Escherichia coli for low carbon-footprint protein and chemical production. Green Chem. https://doi.org/10.1039/D1GC00456E Tan SI, You SC, Shih IT, Ng IS (2020a) Quantification, regulation and production of 5-aminolevulinic acid by green fluorescent protein in recombinant Escherichia coli. J Biosci Bioeng 129:387–394 Tan SI, Yu PJ, Ng IS (2020b) CRISPRi-mediated programming essential gene can as a direct enzymatic performance evaluation & determination (DEPEND) system. Biotechnol Bioeng 117:2842–2851 Tangprasittipap A, Prasertsan P, Choorit W, Sasaki K (2007) Biosynthesis of intracellular 5-aminolevulinic acid by a newly identified halotolerant Rhodobacter sphaeroides. Biotechnol Lett 29:773–778 Tran NT, Pham DN, Kim CJ (2019) Production of 5-aminolevulinic acid by recombinant Streptomyces coelicolor expressing hemA from Rhodobacter sphaeroides. Biotechnol Bioprocess Eng 24:488–499 Tripetch P, Srzednicki G, Borompichaichartkul C (2013) Separation process of 5-aminolevulinic acid from Rhodobacter spaeroides for increasing value of agricultural product by ion exchange chromatography. Acta Hortic 1011:265–271 Van der Werf MJ, Zeikus JG (1996) 5-Aminolevulinate production by Escherichia coli containing the Rhodobacter sphaeroides hemA gene. Appl Environ Microbiol 62:3560–3566 Venosa DG, Fukuda H, Perotti C, Batlle A, Casas A (2004) A method for separating ALA from ALA derivatives using ionic exchange extraction. J Photochem Photobiol B: Biol 75:157–163 Verderber E, Lucast LJ, Van Dehy JA, Cozart P, Etter JB, Best EA (1997) Role of the hemA gene product and delta-aminolevulinic acid in regulation of Escherichia coli heme synthesis. J Bacteriol Res 179:4583–4590 Volland C, Felix F (1984) Isolation and properties of 5-aminolevulinate synthase from the yeast Saccharomyces cerevisiae. Eur J Biochem 142:551–557 Wang WY, Huang DD, Stachon D, Gough SP, Kannangara CG (1984) Purification, characterization, and fractionation of the δ-aminolevulinic acid synthesizing enzymes from light-grown Chlamydomonas reinhardtii cells. Plant Physiol 74:569–575 Wild PJ, Krieg RC, Seidl J, Stoehr R, Reher K, Hofmann C et al (2005) RNA expression profiling of normal and tumor cells following photodynamic therapy with 5-aminolevulinic acid–induced protoporphyrin IX in vitro. Mol Cancer Ther 4:516–528 Wu Y, Jin X, Liao W, Hu L, Dawuda MM, Zhao X et al (2018) 5-Aminolevulinic acid (ALA) alleviated salinity stress in cucumber seedlings by enhancing chlorophyll synthesis pathway. Front Plant Sci 9:635 Xie L, Hall D, Eiteman MA, Altman E (2003) Optimization of recombinant aminolevulinate synthase production in Escherichia coli using factorial design. Appl Microbiol Biotechnol 63:267–273 Xue C, Yu TH, Ng IS (2021) Engineering pyridoxal kinase PdxY-integrated Escherichia coli strain and optimization for high-level 5-aminolevulinic acid production. J Taiwan Inst Chem Eng 120:49–58 Yang J, Li Z, Fu W, Lin Y, Lin J, Cen P (2013) Improved 5-aminolevulinic acid production with recombinant Escherichia coli by a short-term dissolved oxygen shock in fed-batch fermentation. Chin J Chem Eng 21:1291–1295 Yang X, Palasuberniam P, Kraus D, Chen B (2015) Aminolevulinic acid-based tumor detection and therapy: molecular mechanisms and strategies for enhancement. Int J Mol Sci 16:25865–25880 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. Appl Environ Microbiol 82:2709–2717 Yang HJ, Lee KH, Lim HJ, Kim DM (2019) Tandem cell-free protein synthesis as a tool for rapid screening of optimal molecular chaperones. Biotechnol J 14:e1800523 Yang Y, Zhang Y, Zou X, Guo X, Lin H (2019b) Perspective clinical study on effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating condylomata acuminata in pregnancy. Photodiagn Photodyn Ther 25:63–65 Yang D, Park SY, Park YS, Eun H, Lee SY (2020) Metabolic engineering of Escherichia coli for natural product biosynthesis. Trends Biotechnol 38:745–765 Yi YC, Ng IS (2020) Establishment of toolkit and T7RNA polymerase/promoter system in Shewanella oneidensis MR-1. J Taiwan Inst Chem Eng 109:8–14 Yi YC, Ng IS (2021) Redirection of metabolic flux in Shewanella oneidensis MR-1 by CRISPRi and modular design for 5-aminolevulinic acid production. Bioresour Bioprocess 8:1–11 Yu X, Jin H, Liu W, Wang Q, Qi Q (2015) Engineering Corynebacterium glutamicum to produce 5-aminolevulinic acid from glucose. Microb Cell Fact 14:183 Yu TH, Yi YC, Shih IT, Ng IS (2020) Enhanced 5-aminolevulinic acid production by co-expression of codon-optimized hemA gene with chaperone in genetic engineered Escherichia coli. Appl Biochem Biotechnol 191:299–312 Zhang L, Chen J, Chen N, Sun J, Zheng P, Ma Y (2013) Cloning of two 5-aminolevulinic acid synthase isozymes HemA and HemO from Rhodopseudomonas palustris with favorable characteristics for 5-aminolevulinic acid production. Biotechnol Lett 35:763–768 Zhang J, Kang Z, Chen J, Du G (2015) Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli. Sci Rep 5:8584 Zhang J, Kang Z, Ding W, Chen J, Du G (2016) Integrated optimization of the in vivo heme biosynthesis pathway and the in vitro iron concentration for 5-aminolevulinate production. Appl Biochem 178:1252–1262 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 8:424–427 Zhang J, Rang Z, Qian S, Qiu L, Chen J, Du G (2018a) Construction of recombinant Saccharomyces cerevisiae for production of 5-aminolevulinic acid. J Food Sci Biotechnol 37:232–239 Zhang X, Zhang J, Xu J, Zhao Q, Wang Q, Qi Q (2018b) Engineering Escherichia coli for efficient coproduction of polyhydroxyalkanoates and 5-aminolevulinic acid. J Ind Microbiol Biotechnol 45:43–51 Zhang J, Weng H, Zhou Z, Du G, Kang Z (2019) Engineering of multiple modular pathways for high-yield production of 5-aminolevulinic acid in Escherichia coli. Bioresour Technol 274:353–360 Zhang B, Ye BC (2018) Pathway engineering in Corynebacterium glutamicum S9114 for 5-aminolevulinic acid production. 3 Biotech 8:247 Zhang J, Wang Z, Su T, Sun H, Zhu Y, Qi Q, Wang Q (2020) Tuning the binding affinity of heme-responsive biosensor for precise and dynamic pathway regulation. iScience 23(5):101067 Zhang C, Li Y, Zhu F, Li Z, Lu N, Li Y et al (2020) Metabolic engineering of an auto-regulated Corynebacterium glutamicum chassis for biosynthesis of 5-aminolevulinic acid. Bioresour Technol 318:124064 Zhao XR, Choi KR, Lee SY (2018) Metabolic engineering of Escherichia coli for secretory production of free haem. Nat Catal 1:720–728 Zhou L, Ren J, Li Z, Nie J, Wang C, Zeng AP (2019) Characterization and engineering of a Clostridium glycine riboswitch and its use to control a novel metabolic pathway for 5-aminolevulinic acid production in Escherichia coli. ACS Synth Biol 8:2327–2335 Zhu C, Chen J, Wang Y, Wang L, Guo X, Chen N et al (2019) Enhancing 5-aminolevulinic acid tolerance and production by engineering the antioxidant defense system of Escherichia coli. Biotechnol Bioeng 116:2018–2028 Zhu Y, Zhou C, Wang Y, Li C (2020) Transporter engineering for microbial manufacturing. Biotechnol J. 15:1900494 Zou Y, Chen T, Feng L, Zhang S, Xing D, Wang Z (2017) Enhancement of 5-aminolevulinic acid production by metabolic engineering of the glycine biosynthesis pathway in Corynebacterium glutamicum. Biotechnol Lett 39:1369–1374