792
Views
2
CrossRef citations to date
0
Altmetric
Review Articles

Bioproduction of porphyrins, phycobilins, and their proteins using microbial cell factories: engineering, metabolic regulations, challenges, and perspectives

, , , , , & show all
Pages 373-387 | Received 07 Sep 2022, Accepted 03 Jan 2023, Published online: 12 Feb 2023

References

  • Auwarter W, Ecija D, Klappenberger F, et al. Porphyrins at interfaces. Nat Chem. 2015;7(2):105–120.
  • Dailey HA, Dailey TA, Gerdes S, et al. Prokaryotic Heme biosynthesis: multiple pathways to a common essential product. Microbiol Mol Biol Rev. 2017;81(1):e00048-16.
  • Ledermann B, Aras M, Frankenberg-Dinkel N. Biosynthesis of cyanobacterial light-harvesting pigments and their assembly into phycobiliproteins. Berlin: Springer; 2017.
  • Burgie ES, Vierstra RD. Phytochromes: an atomic perspective on photoactivation and signaling. Plant Cell. 2014;26(12):4568–4583.
  • Thomas DT, DelCimmuto NR, Flack KD, et al. Reactive oxygen species (ROS) and antioxidants as immunomodulators in exercise: implications for heme oxygenase and bilirubin. Antioxidants. 2022;11(2):179.
  • Liu Y, Liu CZ, Wang ZK, et al. Supramolecular organic frameworks improve the safety of clinically used porphyrin photodynamic agents and maintain their antitumor efficacy. Biomaterials. 2022;284:121467.
  • Cuesta V, Singh MK, Gutierrez-Fernandez E, III, et al. Porphyrin Was used as an electron acceptor for efficient organic solar cells. ACS Appl Mater Interfaces. 2022;14(9):11708–11717.
  • Hu H, Wang H, Yang Y, et al. A bacteria-responsive porphyrin for adaptable photodynamic/photothermal therapy. Angew Chem Int Ed Engl. 2022;61(23):e202200799.
  • Senge MO, Sergeeva NN, Hale KJ. Classic highlights in porphyrin and porphyrinoid total synthesis and biosynthesis. Chem Soc Rev. 2021;50(7):4730–4789.
  • In MJ, Kim DC, Chae HJ, et al. Effects of degree of hydrolysis and pH on the solubility of heme-iron enriched peptide in hemoglobin hydrolysate. Biosci Biotechnol Biochem. 2003;67(2):365–367.
  • Espinas NA, Kobayashi K, Takahashi S, et al. Evaluation of unbound free heme in plant cells by differential acetone extraction. Plant Cell Physiol. 2012;53(7):1344–1354.
  • Ding ZK, Xu YQ. Purification and characterization of biliverdin IXalpha from atlantic salmon (Salmo salar) bile. Biochemistry. 2002;67(8):927–932.
  • Li WJ, Su HN, Pu Y, et al. Phycobiliproteins: molecular structure, production, applications, and prospects. Biotechnol Adv. 2019;37(2):340–353.
  • Lee SY, Kim HU, Chae TU, et al. A comprehensive metabolic map for production of bio-based chemicals. Nat Catal. 2019;2(10):942–944.
  • Joo YC, You SK, Shin SK, et al. Bio-based production of dimethyl itaconate from rice wine waste-derived itaconic acid. Biotechnol J. 2017;12(11):1700114.
  • Baritugo KA, Kim HT, David Y, et al. Enhanced production of gamma-aminobutyrate (GABA) in recombinant Corynebacterium glutamicum strains from empty fruit bunch biosugar solution. Microb Cell Fact. 2018;17:129.
  • Joo YC, Ko YJ, You SK, et al. Creating a new pathway in Corynebacterium glutamicum for the production of taurine as a food additive. J Agric Food Chem. 2018;66(51):13454–13463.
  • Lee ME, Ko YJ, Hwang DH, et al. Surface display of enzyme complex on Corynebacterium glutamicum as a whole cell biocatalyst and its consolidated bioprocessing using fungal-pretreated lignocellulosic biomass. Bioresour Technol. 2022;362:127758.
  • Ko YJ, Kim M, You SK, et al. Animal-free heme production for artificial meat in Corynebacterium glutamicum via systems metabolic and membrane engineering. Metab Eng. 2021;66:217–228.
  • Li WJ, Ma CB, Ge BS, et al. Biosynthesis and preparation of phycoerythrobilin in recombinant Escherichia coli. J Appl Phycol. 2021;33(3):1673–1683.
  • Ma CB, Li WJ, Ge BS, et al. Biosynthesis of phycocyanobilin in recombinant Escherichia coli. J Ocean Limnol. 2020;38(2):529–538.
  • Ma Q, Lan DM, Shao AN, et al. Red fluorescent protein from cyanobacteriochrome chromophorylated with phycocyanobilin and biliverdin. Anal Biochem. 2022;642:114557.
  • Nagano S, Sadeghi M, Balke J, et al. Improved fluorescent phytochromes for in situ imaging. Sci Rep. 2022;12(1):5587.
  • Zhao XR, Gao HX, Wang YQ, et al. Efficient synthesis of phycocyanobilin by combinatorial metabolic engineering in Escherichia coli. ACS Synth Biol. 2022;11(6):2089–2097.
  • Kuwasaki Y, Suzuki K, Yu G, et al. A red light-responsive photoswitch for deep tissue optogenetics. Nat Biotechnol. 2022;40(11):1672–1679.
  • Choi KR, Yu HE, Lee SY. Production of zinc protoporphyrin IX by metabolically engineered Escherichia coli. Biotechnol Bioeng. 2022;119:3319–3325.
  • Chen GYE, Canniffe DP, Barnett SFH, et al. Complete enzyme set for chlorophyll biosynthesis in Escherichia coli. Sci Adv. 2018;4(1):eaaq1407.
  • Ko YJ, Joo YC, Hyeon JE, et al. Biosynthesis of organic photosensitizer Zn-porphyrin by diphtheria toxin repressor (DtxR)-mediated global upregulation of engineered heme biosynthesis pathway in Corynebacterium glutamicum. Sci Rep. 2018;8:14460.
  • Zhao XR, Choi KR, Lee SY. Metabolic engineering of Escherichia coli for secretory production of free haem. Nat Catal. 2018;1(9):720–728.
  • Chen LH, Bai HT, Xu JF, et al. Supramolecular porphyrin photosensitizers: controllable disguise and photoinduced activation of antibacterial behavior. ACS Appl Mater Interfaces. 2017;9(16):13950–13957.
  • Choi KR, Yu HE, Lee H, et al. Improved production of heme using metabolically engineered Escherichia coli. Biotechnol Bioeng. 2022;119:3178–3193.
  • Hyeon JE, Jeong DW, Ko YJ, et al. Biomimetic magnetoelectric nanocrystals synthesized by polymerization of heme as advanced nanomaterials for biosensing application. Biosens Bioelectron. 2018;114:1–9.
  • Lee JH, Kim HR, Lee JH, et al. Enhanced in-vitro hemozoin polymerization by optimized process using histidine-rich protein II (HRPII). Polymers. 2019;11(7):1162.
  • Seok J, Ko YJ, Lee ME, et al. Systems metabolic engineering of Corynebacterium glutamicum for the bioproduction of biliverdin via protoporphyrin independent pathway. J Biol Eng. 2019;13:58.
  • Ge BS, Chen Y, Yu Q, et al. Regulation of the heme biosynthetic pathway for combinational biosynthesis of phycocyanobilin in Escherichia coli. Process Biochem. 2018;71:23–30.
  • Chen HX, Jiang P. Metabolic engineering of Escherichia coli for efficient biosynthesis of fluorescent phycobiliprotein. Microb Cell Fact. 2019;18:58.
  • Liu L, Martinez JL, Liu Z, et al. Balanced globin protein expression and heme biosynthesis improve production of human hemoglobin in Saccharomyces cerevisiae. Metab Eng. 2014;21:9–16.
  • Shankar S, Hoyt MA. Expression constructions and methods of genetically engineering methylotrophic yeast. WO 2016/183163A12017.
  • Shao YR, Xue CL, Liu WQ, et al. High-level secretory production of leghemoglobin in Pichia pastoris through enhanced globin expression and heme biosynthesis. Bioresour Technol. 2022;363:127884.
  • Perkins LJ, Weaver BR, Buller AR, et al. De novo biosynthesis of a nonnatural cobalt porphyrin cofactor in E. coli and incorporation into hemoproteins. Proc Natl Acad Sci U S A. 2021;118(16):e2017625118.
  • Shin AY, Han YJ, Song PS, et al. Expression of recombinant full-length plant phytochromes assembled with phytochromobilin in Pichia pastoris. FEBS Lett. 2014;588(17):2964–2970.
  • Liu S, Chen H, Qin S, et al. Highly soluble and stable recombinant holo-phycocyanin alpha subunit expressed in Escherichia coli. Biochem Eng J. 2009;48(1):58–64.
  • Puzorjov A, Dunn KE, McCormick AJ. Production of thermostable phycocyanin in a mesophilic cyanobacterium. Metab Eng Commun. 2021;13:e00175.
  • Wang L, Elliott M, Elliott T. Conditional stability of the HemA protein (glutamyl-tRNA reductase) regulates heme biosynthesis in Salmonella typhimurium. J Bacteriol. 1999;181(4):1211–1219.
  • Srivastava A, Beale SI. Glutamyl-tRNA reductase of Chlorobium vibrioforme is a dissociable homodimer that contains one tightly bound heme per subunit. J Bacteriol. 2005;187(13):4444–4450.
  • Levican G, Katz A, de Armas M, et al. Regulation of a glutamyl-tRNA synthetase by the heme status. Proc Natl Acad Sci U S A. 2007;104(9):3135–3140.
  • Burnham BF, Pierce WS, Williams KR, et al. Control of porphyrin biosynthesis through a negative-feedback mechanism - studies with preparations of delta-aminolaevulate synthetase and delta-aminolaevulate dehydratase from Rhodopseudomonas spheroides. Biochem J. 1963;87(3):462–472.
  • Ikushiro H, Nagami A, Takai T, et al. Heme-dependent inactivation of 5-aminolevulinate synthase from Caulobacter crescentus. Sci Rep. 2018;8(1):14228.
  • Yu XL, Jin HY, Liu WJ, et al. Engineering Corynebacterium glutamicum to produce 5-aminolevulinic acid from glucose. Microb Cell Fact. 2015;14:183.
  • Sasaki K, Watanabe M, Nishio N. Inhibition of 5-aminolevulinic acid (ALA) dehydratase by undissociated levulinic acid during ALA extracellular formation by Rhodobacter sphaeroides. Biotechnol Lett. 1997;19(5):421–424.
  • Nunez L, Rodriguez-Torres A, Cerdan ME. Regulatory elements in the KlHEM1 promoter. Biochim Biophys Acta Gene Regul Mech. 2008;1779(2):128–133.
  • Lee DH, Jun WJ, Kim KM, et al. Inhibition of 5-aminolevulinic acid dehydratase in recombinant Escherichia coli using D-glucose. Enzyme Microb Technol. 2003;32(1):27–34.
  • Zhang JL, Kang Z, Chen J, et al. Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli. Sci Rep. 2015;5:8584.
  • Keng T. HAP1 and ROX1 form a regulatory pathway in the repression of HEM13 transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1992;12(6):2616–2623.
  • Nellen-Anthamatten D, Rossi P, Preisig O, et al. Bradyrhizobium japonicum FixK2, a crucial distributor in the FixLJ-dependent regulatory Cascade for control of genes inducible by low oxygen levels. J Bacteriol. 1998;180(19):5251–5255.
  • Smart JL, Willett JW, Bauer CE. Regulation of hem gene expression in Rhodobacter capsulatus by redox and photosystem regulators RegA, CrtJ, FnrL, and AerR. J Mol Biol. 2004;342(4):1171–1186.
  • Smart JL, Bauer CE. Tetrapyrrole biosynthesis in Rhodobacter capsulatus is transcriptionally regulated by the heme-binding regulatory protein, HbrL. J Bacteriol. 2006;188(4):1567–1576.
  • Ranson-Olson B, Jones DF, Donohue TJ, et al. In vitro and in vivo analysis of the role of PrrA in Rhodobacter sphaeroides 2.4.1 hemA gene expression. J Bacteriol. 2006;188(9):3208–3218.
  • Yang J, Panek HR, O'Brian MR. Oxidative stress promotes degradation of the Irr protein to regulate haem biosynthesis in Bradyrhizobium japonicum. Mol Microbiol. 2006;60(1):209–218.
  • Bibb LA, Kunkle CA, Schmitt MP. The ChrA-ChrS and HrrA-HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae. Infect Immun. 2007;75(5):2421–2431.
  • Frunzke J, Gatgens C, Brocker M, et al. Control of heme homeostasis in Corynebacterium glutamicum by the two-component system HrrSA. J Bacteriol. 2011;193(5):1212–1221.
  • Mancini S, Imlay JA. The induction of two biosynthetic enzymes helps Escherichia coli sustain heme synthesis and activate catalase during hydrogen peroxide stress. Mol Microbiol. 2015;96(4):744–763.
  • Li F, Wang Y, Gong K, et al. Constitutive expression of RyhB regulates the heme biosynthesis pathway and increases the 5-aminolevulinic acid accumulation in Escherichia coli. FEMS Microbiol Lett. 2014;350(2):209–215.
  • Sobotka R, Dühring U, Komenda J, et al. Importance of the cyanobacterial GUN4 protein for chlorophyll metabolism and assembly of photosynthetic complexes. J Biol Chem. 2008;283(38):25794–25802.
  • Liu S, Zhang G, Li X, et al. Microbial production and applications of 5-aminolevulinic acid. Appl Microbiol Biotechnol. 2014;98(17):7349–7357.
  • Fuchs J, Weber S, Kaufmann R. Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy. Free Radical Biol Med. 2000;28(4):537–548.
  • Hoppe M, Brun B, Larsson MP, et al. Heme iron-based dietary intervention for improvement of iron status in young women. Nutrition. 2013;29(1):89–95.
  • Anderson KE, Collins SD. Hemin treatment for acute porphyria: implications for clinical practice of an open-label study of 130 patients. J Invest Med. 2006;54(1):S290–S290.
  • Waltz E. Appetite grows for biotech foods with health benefits. Nat Biotechnol. 2019;37(6):573–575.
  • Amos-Tautua BM, Songca SP, Oluwafemi OS. Application of porphyrins in antibacterial photodynamic therapy. Molecules. 2019;24(13):2456.
  • Wainwright M, Smalley H, Flint C. The use of photosensitisers in acne treatment. J Photochem Photobiol B. 2011;105(1):1–5.
  • Takasaki AA, Aoki A, Mizutani K, et al. Application of antimicrobial photodynamic therapy in periodontal and peri-implant diseases. Periodontol. 2009;51:109–140.
  • Zou Q, Abbas M, Zhao L, et al. Biological photothermal nanodots based on self-assembly of peptide-porphyrin conjugates for antitumor therapy. J Am Chem Soc. 2017;139(5):1921–1927.
  • Toriya M, Yamamoto M, Saeki K, et al. Antitumor effect of photodynamic therapy with zincphyrin, zinc-coproporphyrin III, in mice. Biosci Biotechnol Biochem. 2001;65(2):363–370.
  • Alibabaei L, Wang MK, Giovannetti R, et al. Application of Cu(II) and Zn(II) coproporphyrins as sensitizers for thin film dye sensitized solar cells. Energy Environ Sci. 2010;3(7):956–961.
  • Mathew S, Yella A, Gao P, et al. Dye-sensitized solar cells with 13% efficiency achieved through the molecular engineering of porphyrin sensitizers. Nat Chem. 2014;6(3):242–247.
  • Park JM, Lee JH, Jang WD. Applications of porphyrins in emerging energy conversion technologies. Coord Chem Rev. 2020;407:213157.
  • Natali M, Deponti E, Vilona D, et al. A Bioinspired system for light-driven water oxidation with a porphyrin sensitizer and a tetrametallic molecular catalyst. Eur J Inorg Chem. 2015;2015(21):3467–3477.
  • Ryu WH, Gittleson FS, Thomsen JM, et al. Heme biomolecule as redox mediator and oxygen shuttle for efficient charging of lithium-oxygen batteries. Nat Commun. 2016;7:12925.
  • Ziberna L, Martelanc M, Franko M, et al. Bilirubin is an endogenous antioxidant in human vascular endothelial cells. Sci Rep. 2016;6:29240.
  • Sonani RR, Rastogi RP, Patel R, et al. Recent advances in production, purification and applications of phycobiliproteins. WJBC. 2016;7(1):100–109.
  • Shu X, Royant A, Lin MZ, et al. Mammalian expression of infrared fluorescent proteins engineered from a bacterial phytochrome. Science. 2009;324(5928):804–807.
  • Uda Y, Goto Y, Oda S, et al. Efficient synthesis of phycocyanobilin in mammalian cells for optogenetic control of cell signaling. Proc Natl Acad Sci U S A. 2017;114(45):11962–11967.
  • Ramzi AB, Hyeon JE, Kim SW, et al. 5-Aminolevulinic acid production in engineered Corynebacterium glutamicum via C5 biosynthesis pathway. Enzyme Microb Technol. 2015;81:1–7.
  • Anzaldi LL, Skaar EP. Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens. Infect Immun. 2010;78(12):4977–4989.
  • Mike LA, Dutter BF, Stauff DL, et al. Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus. Proc Natl Acad Sci U S A. 2013;110(20):8206–8211.
  • Chiu FY, Chen YR, Tu SL. Electrostatic interaction of phytochromobilin synthase and ferredoxin for biosynthesis of phytochrome chromophore. J Biol Chem. 2010;285(7):5056–5065.
  • Kim GB, Kim WJ, Kim HU, et al. Machine learning applications in systems metabolic engineering. Curr Opin Biotechnol. 2020;64:1–9.
  • Kim GB, Gao Y, Palsson BO, et al. DeepTFactor: a deep learning-based tool for the prediction of transcription factors. Proc Natl Acad Sci USA. 2021;118(2):e2021171118.
  • Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–589.
  • Choi KR, Jang WD, Yang D, et al. Systems metabolic engineering strategies: integrating systems and synthetic biology with metabolic engineering. Trends Biotechnol. 2019;37(8):817–837.
  • Toriya M, Yaginuma S, Murofushi S, et al. Zincphyrin, a novel coproporphyrin-III with zinc from Streptomyces sp. J Antibiot. 1993;46(1):196–200.
  • Lee MJ, Kim HJ, Lee JY, et al. Effect of gene amplifications in porphyrin pathway on heme biosynthesis in a recombinant Escherichia coli. J Microbiol Biotechnol. 2013;23(5):668–673.
  • Kwon SJ, de Boer AL, Petri R, et al. 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. 2003;69(8):4875–4883.
  • Kwon OH, Kim S, Hahm DH, et al. Potential application of the recombinant Escherichia coli-synthesized heme as a bioavailable iron source. J Microbiol Biotechnol. 2009;19(6):604–609.
  • Choi SI, Park J, Kim P. Heme derived from Corynebacterium glutamicum: a potential iron additive for swine and an electron carrier additive for lactic acid bacterial culture. J Microbiol Biotechnol. 2017;27(3):500–506.
  • Chen D, Brown JD, Kawasaki Y, et al. Scalable production of biliverdin IX alpha by Escherichia coli. BMC Biotechnol. 2012;12:89.
  • Ge B, Li Y, Sun H, et al. Combinational biosynthesis of phycocyanobilin using genetically-engineered Escherichia coli. Biotechnol Lett. 2013;35(5):689–693.
  • Stiefelmaier J, Ledermann B, Sorg M, et al. Pink bacteria-production of the pink chromophore phycoerythrobilin with Escherichia coli. J Biotechnol. 2018;274:47–53.
  • Chen YR, Su YS, Tu SL. Distinct phytochrome actions in nonvascular plants revealed by targeted inactivation of phytobilin biosynthesis. Proc Natl Acad Sci U S A. 2012;109(21):8310–8315.
  • Ledermann B, Beja O, Frankenberg-Dinkel N. New biosynthetic pathway for pink pigments from uncultured oceanic viruses. Environ Microbiol. 2016;18(12):4337–4347.
  • Rockwell NC, Martin SS, Li FW, et al. The phycocyanobilin chromophore of streptophyte algal phytochromes is synthesized by HY2. New Phytol. 2017;214(3):1145–1157.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.