Prodigiosin: a fascinating and the most versatile bioactive pigment with diverse applications

Abstract

Synthetic pigments pose toxicity and harmful impacts on humans and environment. In this context, the exploration of microbial sources for producing natural pigments that are useful in various industrial applications is gaining prominence. Microbial pigments give nature its color and are a novel class of chemicals with diversity of biological functions including antibacterial, anti-mycotic, antimalarial, immuno-modulating, and anticancer properties. Microbial pigment sources have been acknowledged to be extraordinarily valuable and are in great demand, attributable to their varied uses in the food and cosmetic industries, textile, and pharmaceutical industries. Prodigiosin has recently been suggested as the most potential choice and promising biomolecule with multifaceted applications, including antimicrobial, immunosuppressive, antimalarial, antineoplastic, and anticancer properties. Prodigiosin has recently received a renewed interest owing to its reported characteristics of having profound biological activities. The focus of this review article is the most important qualities and prospective uses of prodigiosin pigment.

Keywords

Bioactive pigment / Prodigiosin / Biological activities / Anticancer / Antimicrobial / Antifungal

References

[1.] Mapari SA, Nielsen KF, Larsen TO, Frisvad JC, Meyer AS, Thrane U. Exploring fungal biodiversity for the production of water-soluble pigments as potential natural food colorants. Curr Opin Biotechnol, 2005, 16(2): 231-238.

[2.] Numan M, Bashir S, Mumtaz R, Tayyab S, Rehman NU, Khan AL, Shinwari ZK, Al-Harrasi A. Therapeutic applications of bacterial pigments: a review of current status and future opportunities. 3 Biotech, 2018, 8: 1-15.

[3.] Koyande AK, Show PL, Guo R, Tang B, Ogino C, Chang JS. Bio-processing of algal bio-refinery: a review on current advances and future perspectives. Bioengineered, 2019, 10(1): 574-592.

[4.] Chiba S, Tsuyoshi N, Fudou R, Ojika M, Murakami Y, Ogoma Y, Oguchi M, Yamanaka S. Magenta pigment produced by fungus. J Gen Appl Microbiol, 2006, 52(4): 201-207.

[5.] Ramesh C, Vinithkumar NV, Kirubagaran R, Venil CK, Dufossé L. Multifaceted applications of microbial pigments: current knowledge, challenges and future directions for public health implications. Microorganisms, 2019, 7(7): 186.

[6.] Darshan N, Manonmani HK. Prodigiosin and its potential applications. J Food Sci Technol, 2015, 52: 5393-5407.

[7.] Wang SL, Nguyen VB, Doan CT, Tran TN, Nguyen MT, Nguyen AD. Production and potential applications of bioconversion of chitin and protein-containing fishery byproducts into prodigiosin: a review. Molecules, 2020, 25(12): 2744.

[8.] Jeong YJ, Kim HJ, Kim S, et al. Enhanced large-scale production of Hahellachejuensis-derived prodigiosin and evaluation of its bioactivity. J Microbiol Biotechnol, 2021, 31(12): 1624-1631.

[9.] Paul T, Bandyopadhyay TK, Mondal A, et al. A comprehensive review on recent trends in production, purification, and applications of prodigiosin. Biomass Convers Biorefin, 2022, 12: 1409-1431.

[10.] Matsuyama T, Murakami T, Fujita M, Fujita S, Yano I. Extracellular vesicle formation and biosurfactant production by Serratia marcescens. Microbiology, 1986, 132(4): 865-875.

[11.] Kobayashi N, Ichikawa Y. Separation of the prodigiosin-localizing crude vesicles which retain the activity of protease and nuclease in Serratia marcescens. Microbiol Immunol, 1991, 35(8): 607-614.

[12.] Qadri SH, Williams RP. Role of methionine in biosynthesis of prodigiosin by Serratia marcescens. J Bacteriol, 1973, 116(3): 1191-1198.

[13.] Gerber NN. Prodigiosin-like pigments. CRC Crit Rev Microbiol, 1975, 3(4): 469-485.

[14.] Soto-Cerrato V, Llagostera E, Montaner B, Scheffer GL, Perez-Tomas R. Mitochondria-mediated apoptosis operating irrespective of multidrug resistance in breast cancer cells by the anticancer agent prodigiosin. Biochem Pharmacol, 2004, 68(7): 1345-1352.

[15.] Lee JS, Kim YS, Park S, Kim J, Kang SJ, Lee MH, Ryu S, Choi JM, Oh TK, Yoon JH. Exceptional production of both prodigiosin and cycloprodigiosin as major metabolic constituents by a novel marine bacterium, Zooshikella rubidus S1–1. Appl Environ Microbiol, 2011, 77(14): 4967-4973.

[16.] Boric M, Danevcic T, Stopar D. Prodigiosin from Vibrio sp. DSM 14379; a new UV-protective pigment. Microb Ecol, 2011, 62: 528-536.

[17.] Park H, Lee SG, Kim TK, Han SJ, Yim JH. Selection of extraction solvent and temperature effect on stability of the algicidal agent prodigiosin. Biotechnol Bioprocess Eng, 2012, 17: 1232-1237.

[18.] Panesar R, Kaur S, Panesar PS. Production of microbial pigments utilizing agro-industrial waste: a review. Curr Opin Food Sci, 2015, 1: 70-76.

[19.] Genes C, Baquero E, Echeverri F, Maya JD, Triana O. Mitochondrial dysfunction in Trypanosoma cruzi: the role of Serratia marcescens prodigiosin in the alternative treatment of Chagas disease. Parasit Vectors, 2011, 4(1): 1-8.

[20.] Goncharova EA, Goncharov DA, Fehrenbach M, Khavin I, Ducka B, Hino O, Colby TV, Merrilees MJ, Haczku A, Albelda SM, Krymskaya VP. Prevention of alveolar destruction and airspace enlargement in a mouse model of pulmonary lymphangioleiomyomatosis (LAM). Sci Transl Med, 2012, 4(154): 154ra134.

[21.] Dong R, Gu L, Guo C, Xun F, Liu J. Effect of PGPR Serratia marcescens BC-3 and AMF Glomus intraradices on phytoremediation of petroleum contaminated soil. Ecotoxicology, 2014, 23: 674-680.

[22.] Danevcic T, Boric Vezjak M, Tabor M, Zorec M, Stopar D. Prodigiosin induces autolysins in actively grown Bacillus subtilis cells. Front Microbiol, 2016, 7: 27.

[23.] Davient B, Ng JPZ, Xiao Q, Li L, Yang L. Comparative Transcriptomics unravels Prodigiosin's potential cancer-specific activity between human small airway epithelial cells and lung adenocarcinoma cells. Front Oncol, 2018, 8: 573.

[24.] Venil CK, Zakaria ZA, Ahmad WA. Bacterial pigments and their applications. Process Biochem, 2013, 48(7): 1065-1079.

[25.] Ren Y, Fu R, Fang K, Xie R, Hao L, Chen W, Shi Z. Clean dyeing of acrylic fabric by sustainable red bacterial pigment based on nano-suspension system. J Clean Prod, 2021, 281.

[26.] Liu J, Yang M, Tan J, Yin Y, Yang Y, Wang C. pH-responsive discoloration silk fibroin films based on prodigiosin from microbial fermentation. Dyes Pigm, 2022, 198.

[27.] Klein AS, Domröse A, Bongen P, Brass HU, Classen T, Loeschcke A, Drepper T, Laraia L, Sievers S, Jaeger KE, Pietruszka J. New prodigiosin derivatives obtained by mutasynthesis in Pseudomonas putida. ACS Synth Biol, 2017, 6(9): 1757-1765.

[28.] Perez-Tomas R, Montaner B, Llagostera E, Soto-Cerrato V. The prodigiosins, proapoptotic drugs with anticancer properties. Biochem Pharmacol, 2003, 66(8): 1447-1452.

[29.] Williamson NR, Fineran PC, Gristwood T, Chawrai SR, Leeper FJ, Salmond GP. Anticancer and immunosuppressive properties of bacterial prodiginines. Future Microbiol, 2007, 2: 605-618.

[30.] Soto-Cerrato V, Viñals F, Lambert JR, Pérez-Tomás R. The anticancer agent prodigiosin induces p21WAF1/CIP1 expression via transforming growth factor-beta receptor pathway. Biochem Pharmacol, 2007, 74(9): 1340-1349.

[31.] Perez-Tomas R, Vinas M. New insights on the antitumoral properties of prodiginines. Curr Med Chem, 2010, 17(21): 2222-2231.

[32.] Stankovic N, Senerovic L, Ilic-Tomic T, Vasiljevic B, Nikodinovic-Runic J. Properties and applications of undecylprodigiosin and other bacterial prodigiosins. Appl Microbiol Biotechnol, 2014, 98: 3841-3858.

[33.] Sudhakar C, Shobana C, Selvankumar T, Selvam K. Prodigiosin production from Serratia marcescens strain CSK and their antioxidant, antibacterial, cytotoxic effect and in silico study of caspase-3 apoptotic protein. Biotechnol Appl Biochem, 2022, 69(5): 1984-1997.

[34.] Kimyon Ö, Das T, Ibugo AI, Kutty SK, Ho KK, Tebben J, Kumar N, Manefield M. Serratia secondary metabolite prodigiosin inhibits Pseudomonas aeruginosa biofilm development by producing reactive oxygen species that damage biological molecules. Front Microbiol, 2016, 7: 972.

[35.] Zhang H, Peng Y, Zhang S, Cai G, Li Y, Yang X, Yang K, Chen Z, Zhang J, Wang H, Zheng T. Algicidal effects of prodigiosin on the harmful algae Phaeocystis globosa. Front Microbiol, 2016, 7: 602.

[36.] Azambuja P, Feder D, Garcia ES. Isolation of Serratia marcescens in the midgut of Rhodnius prolixus: impact on the establishment of the parasite Trypanosoma cruzi in the vector. Exp Parasitol, 2004, 107(1–2): 89-96.

[37.] Alihosseini F, Ju K, Lango J, Hammock BD, Sun G. Antibacterial colorants: characterization of prodiginines and their applications on textile materials. Biotechnol Prog, 2008, 24: 742-747.

[38.] Songia S, Mortellaro A, Taverna S, Fornasiero C, Scheiber EA, Erba E, Colotta F, Mantovani A, Isetta AM, Golay J. Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets. J Immunol (Baltimore, Md.: 1950), 1997, 158(8): 3987-3995.

[39.] Someya N, Nakajima M, Watanabe K, Hibi T, Akutsu K. Influence of bacteria isolated from rice plants and rhizospheres on antibiotic production by the antagonistic bacterium Serratia marcescens strain B2. J Gen Plant Pathol, 2003, 69: 342-347.

[40.] You Z, Zhang S, Liu X, Zhang J, Wang Y, Peng Y, Wu W. Insights into the anti-infective properties of prodiginines. Appl Microbiol Biotechnol, 2019, 103: 2873-2887.

[41.] Guryanov I, Naumenko E, Akhatova F, Lazzara G, Cavallaro G, Nigamatzyanova L, Fakhrullin R. Selective cytotoxic activity of prodigiosin@ halloysite nanoformulation. Front Bioeng Biotechnol, 2020, 8: 424.

[42.] Pandey R, Chander R, Sainis KB. Prodigiosins as anti cancer agents: Living upto their name. Curr Pharm Des, 2009, 15(7): 732-741.

[43.] Williams RP, Gott CL, Qadri SH. Induction of pigmentation in nonproliferating cells of Serratia marcescens by addition of single amino acids. J Bacteriol, 1971, 106(2): 444-448.

[44.] Witney FR, Failla ML, Weinberg ED. Phosphate inhibition of secondary metabolism in Serratia marcescens. Appl Environ Microbiol, 1977, 33(5): 1042-1046.

[45.] Sole M, Francia A, Rius N, Loren JG. The role of pH in the ‘glucose effect’on prodigiosin production by non-proliferating cells of Serratia marcescens. Lett Appl Microbiol, 1997, 25(2): 81-84.

[46.] Slater H, Crow M, Everson L, Salmond GP. Phosphate availability regulates biosynthesis of two antibiotics, prodigiosin and carbapenem, in Serratia via both quorum-sensing-dependent and-independent pathways. Mol Microbiol, 2003, 47(2): 303-320.

[47.] Wang SL, Wang CY, Yen YH, Liang TW, Chen SY, Chen CH. Enhanced production of insecticidal prodigiosin from Serratia marcescens TKU011 in media containing squid pen. Process Biochem, 2012, 47(11): 1684-1690.

[48.] Ryazantseva IN, Saakov VS, Andreyeva IN, Ogorodnikova TI, Zuev YF. Response of pigmented Serratia marcescens to the illumination. J Photochem Photobiol B, 2012, 106: 18-23.

[49.] Giri AV, Anandkumar N, Muthukumaran G, Pennathur G. A novel medium for the enhanced cell growth and production of prodigiosin from Serratia marcescens isolated from soil. BMC Microbiol, 2004, 4(1): 1-10.

[50.] Wei YH, Chen WC. Enhanced production of prodigiosin-like pigment from Serratia marcescens SMΔR by medium improvement and oil-supplementation strategies. J Biosci Bioeng, 2005, 99(6): 616-622.

[51.] Araujo HW, Fukushima K, Takaki GM. Prodigiosin production by Serratia marcescens UCP 1549 using renewable-resources as a low cost substrate. Molecules, 2010, 15: 6931-7694.

[52.] Cang S, Sanada M, Johdo O, Ohta S, Nagamatsu Y, Yoshimoto A. High production of prodigiosin by Serratia marcescens grown on ethanol. Biotechnol Lett, 2000, 22: 1761-1765.

[53.] Siva R, Subha K, Bhakta D, Ghosh AR, Babu S. Characterization and enhanced production of prodigiosin from the spoiled coconut. Appl Biochem Biotechnol, 2012, 166: 187-196.

[54.] Pryce LH, Terry FW. Spectrophotometric assay of gene expression: Serratia marcescens pigmentation. Bioscene, 2000, 26(4): 3-13.

[55.] Sujitha S, Rajanarayanan S. Isolation, characterization of 55. Serratia marcescens from marine sediments and evaluation of potentail biological applications. J AdvSci Res., 2020, 11(04 Suppl 9): 51-9.

[56.] Gulani C, Bhattacharya S, Das A. Assessment of process parameters influencing the enhanced production of prodigiosin from Serratia marcescens and evaluation of its antimicrobial, antioxidant and dyeing potentials. Malays J Microbiol, 2012, 8(2): 116-122.

[57.] Liaaen-Jensen S. Isler O. Isolation, reactions. Carotenoids, 1971 Basel Birkhauser Verlag 61-188.

[58.] Hu DX, Withall DM, Challis GL, Thomson RJ. Structure, chemical synthesis, and biosynthesis of prodiginine natural products. Chem Rev, 2016, 116(14): 7818-7853.

[59.] Kimata S, Izawa M, Kawasaki T, Hayakawa Y. Identification of a prodigiosin cyclization gene in the roseophilin producer and production of a new cyclized prodigiosin in a heterologous host. J Antibiot, 2017, 70(2): 196-199.

[60.] Elkenawy NM, Yassin AS, Elhifnawy HN, Amin MA. Optimization of prodigiosin production by Serratia marcescens using crude glycerol and enhancing production using gamma radiation. Biotechnol Rep, 2017, 14: 47-53.

[61.] Gummadidala PM, Chen YP, Beauchesne KR, Miller KP, Mitra C, Banaszek N, Velez-Martinez M, Moeller PD, Ferry JL, Decho AW, Chanda A. Aflatoxin-exposure of Vibrio gazogenes as a novel system for the generation of aflatoxin synthesis inhibitors. Front Microbiol, 2016, 7: 814.

[62.] Kumar TS, Aparna H. Anti-biofouling activity of Prodigiosin, a pigment extracted from Serratia marcescens. Int J Curr Microbiol App Sci, 2014, 3(5): 712-725.

[63.] Sumathi C, MohanaPriya D, Swarnalatha S, Dinesh MG, Sekaran G. Production of prodigiosin using tannery fleshing and evaluating its pharmacological effects. Sci World J, 2014, 2014: 1.

[64.] Siva R, Subha K, Bhakta D, Ghosh AR, Babu S. Characterization and enhanced production of prodigiosin from the spoiled coconut. Appl Biochem Biotechnol., 2012, 6(1): 187-96.

[65.] Paul T, Bandyopadhyay TK, Mondal A, Tiwari ON, Muthuraj M, Bhunia B. A comprehensive review on recent trends in production, purification, and applications of prodigiosin. Biomass Convers Biorefin, 2020, 12: 1409-1431.

[66.] Rakh RR, Dalvi SM, Musle BB, Raut LS. Production, extraction and characterization of red pigment produced by Serratia rubidaea JCM 1240T isolated from soil. Int J Curr Microbiol App Sci, 2017, 6(1): 143-154.

[67.] Andreyeva IN, Ogorodnikova TI. Pigmentation of Serratia marcescens and spectral properties of prodigiosin. Microbiology, 2015, 84(1): 28-33.

[68.] Haddix P, Wenner TF. Spectrophotometric assay of gene expression: Serratia marcescens pigmentation. Bioscene, 2000, 26(4): 3-13.

[69.] Andreeva IN, Ogorodnikova TI. Pigmentation of Serratia marcescens and spectral properties of prodigiosin. Mikrobiologiia., 2015, 84(1): 43-9.

[70.] Andreyeva IN, Gorodnikova TI. Pigmentation of Serratia marcescens and spectral properties of prodigiosin. Microbiology., 2015, 84: 28-33.

[71.] Williamson NR, Fineran PC, Leeper FJ, Salmond GP. The biosynthesis and regulation of bacterial prodiginines. Nat Rev Microbiol, 2006, 4(12): 887-899.

[72.] Weinberg ED. Advan. Microb Physiol, 1970, 4(1): 303-320.

[73.] Yip CH, Yarkoni O, Ajioka J, Wan KL, Nathan S. Recent advancements in high-level synthesis of the promising clinical drug, prodigiosin. Appl Microbiol Biotechnol, 2019, 103: 1667-1680.

[74.] Boger DL, Patel M. Total synthesis of prodigiosin, prodigiosene, and desmethoxyprodigiosin: Diels-Alder reactions of heterocyclic azadienes and development of an effective palladium(II)-promoted 2, 2′-bipyrrole coupling procedure. J Org Chem, 1988, 53(7): 1405-1415.

[75.] Elahian F, Moghimi B, Dinmohammadi F, Ghamghami M, Hamidi M, Mirzaei SA. The anticancer agent prodigiosin is not a multidrug resistance protein substrate. DNA Cell Biol, 2013, 32(3): 90-97.

[76.] Goldschmidt MC, Williams RP. Thiamine-induced formation of the monopyrrole moiety of prodigiosin. J Bacteriol, 1968, 96(3): 609-616.

[77.] Harris AK, Williamson NR, Slater H, Cox A, Abbasi S, Foulds I, Simonsen HT, Leeper FJ, Salmond GP. The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species-and strain-dependent genome context variation. Microbiology, 2004, 150(11): 3547-3560.

[78.] Williamson NR, Simonsen HT, Ahmed RA, Goldet G, Slater H, Woodley L, Leeper FJ, Salmond GP. Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces. Mol Microbiol, 2005, 56(4): 971-989.

[79.] Garneau-Tsodikova S, Dorrestein PC, Kelleher NL, Walsh CT. Protein assembly line components in prodigiosin biosynthesis: characterization of PigA, G, H, I, J. J Am Chem Soc, 2006, 128(39): 12600-12601.

[80.] Feitelson JS, Hopwood DA. Cloning of a Streptomyces gene for an O-methyltransferase involved in antibiotic biosynthesis. Mol Gen Genet MGG, 1983, 190(3): 394-398.

[81.] Sakai-Kawada FE, Yakym CJ, Helmkampf M, Hagiwara K, Ip CG, Antonio BJ, Armstrong E, Ulloa WJ, Awaya JD. Draft genome sequence of marine sponge symbiont Pseudoalteromonas luteoviolacea IPB1, isolated from Hilo, Hawaii. Genome Announc, 2016, 4(5): e01002-e1016.

[82.] Mnif S, Jardak M, Bouizgarne B, Aifa S. Prodigiosin from Serratia: synthesis and potential applications. Asian Pac J Trop Biomed, 2022, 12(6): 233.

[83.] Okamoto H, Sato Z, Sato M, Koiso Y, Iwasaki S, Isaka M. Identification of antibiotic red pigments of Serratia marcescens F-1-1, a biocontrol agent of damping-off of cucumber, and antimicrobial activity against other plant pathogens. Ann Phytopathol Soc Jpn, 1998, 64: 294-298.

[84.] Lapenda JC, Silva PA, Vicalvi MC, Sena KXFR, Nascimento SC. Antimicrobial activity of prodigiosin isolated from Serratia marcescens UFPEDA 398. World J MicrobBiot, 2015, 31: 399-406.

[85.] Mumtaz R, Bashir S, Numan M, Shinwari ZK, Ali M. Pigments from soil bacteria and their therapeutic properties: a mini review. Curr Microbiol, 2019, 76: 783-790.

[86.] Suryawanshi RK, Patil CD, Koli SH, Hallsworth JE, Patil SV. Antimicrobial activity of prodigiosin is attributable to plasma-membrane damage. Nat Prod Res, 2017, 31: 572-577.

[87.] Nwankwo IU, Itaman VO, Chidiebere OL, Nwachukwu MP. Evaluation of antimicrobial activity of prodigiosin produced from Serratia marcescens against some pathogenic bacteria. Futo J Ser, 2017, 3:93-102.

[88.] Stankovic N, Radulovic V, Petkovic M, Vuckovic I, Jadranin M, Vasiljevic B, Nikodinovic-Runic J. Streptomyces sp. JS520 produces exceptionally high quantities of undecylprodigiosin with antibacterial, antioxidative, and UV-protective properties. Appl Microbiol Biotechnol, 2012, 96: 1217-1231.

[89.] Berlanga M, Ruiz N, Hernandez-Borrell J, et al. Role of the outer membrane in the accumulation of quinolones by Serratia marcescens. Can J Microbiol, 2000, 46: 716-722.

[90.] Jimtha CJ, Jishma P, Sreelekha S, Chithra S, Radhakrishnan EK. Antifungal properties of prodigiosin producing rhizospheric Serratia sp. Rhizosphere, 2017, 3: 105-108.

[91.] Li D, Liu J, Wang X, Kong D, Du W, Li H, Hse CY, Shupe T, Zhou D, Zhao K. Biological potential and mechanism of prodigiosin from Serratia marcescens subsp. lawsoniana in human choriocarcinoma and prostate cancer cell lines. Int J Mol Sci, 2018, 19(11): 3465.

[92.] Kim D, Kim JF, Yim JH, Kwon SK, Lee CH, Lee HK. Red to red - the marine bacterium Hahella chejuensis andits product prodigiosin for mitigation of harmful algal blooms. J Microbiol Biotechnol., 2008, 18(10): 1621-9.

[93.] Su C, Xiang Z, Liu Y, Zhao X, Sun Y, Li Z, Li L, Chang F, Chen T, Wen X, Zhou Y, Zhao F. Analysis of the genomic sequences and metabolites of Serratia surfactantfaciensspnov YD25(T) that simultaneously produces prodigiosin and serrawettin W2. BMC Genom, 2016, 17(1): 865.

[94.] You Z, Wang Y, Sun S, Liu X. Progress in microbial production of prodigiosin. Sheng Wu Gong Cheng Xue Bao, 2016, 32(10): 1332-1347.

[95.] Yu C, Ou J, Wang M, Jialielihan N, Liu Y. Elevated survivin mediated multidrug resistance and reduced apoptosis in breast cancer stem cells. J Balkan Union Oncol, 2015, 20(5): 1287-1294.

[96.] Montaner B, Pérez-Tomas R. Prodigiosin-induced apoptosis in human colon cancer cells. Life Sci, 2001, 68: 2025-2036.

[97.] Maheswarappa G, Kavitha D, Vijayarani K, Kumanan K. Prodigiosin as anticancer drug produced from bacteria of termite gut. Indian J Basic Appl Med Res, 2013, 3:257-266.

[98.] Campas C, Dalmau M, Montaner B, et al. Prodigiosin induces apoptosis of B and T cells from B-cell chronic lymphocytic leukemia. Leukemia, 2003, 17(4): 746-750.

[99.] Montaner B, Perez-Tomas R. The prodigiosins: a new family of anticancer drugs. Curr Cancer Drug Targets, 2003, 3: 57-65.

[100.] Perez-Tomas R, Montaner B, Llagostera E, Soto-Cerrato V. The prodigiosins, proapoptotic drugs with anticancer properties. Biochem Pharmacol, 2003, 66: 1447-1452.

[101.] Lin S-R, Chen Y-H, Tseng F-J, Weng C-F. The production and bioactivity of prodigiosin: Quo vadis?. Drug Discov Today, 2020, 25: 828-836.

[102.] Francisco R, Perez-Tomas R, Gimenez-Bonafe P, Soto-Cerrato V, Gimenez-Xavier P, Ambrosio S. Mechanisms of prodigiosin cytotoxicity in human neuroblastoma cell lines. Eur J Pharmacol, 2007, 572: 111-119.

[103.] Picha P, Kale D, Dave I, Pardeshi S. Comparative studies on prodigiosin production by Serratia marcescens using various crude fatty acid sources—its characterization and application. Int J Curr Microbiol Appl Sci, 2015, 2:254-267.

[104.] Lazaro JE, Nitcheu J, Predicala RZ, Mangalindan GC, Nesslany F, Marzin D, Concepcion GP, Diquet B. Heptyl prodigiosin, a bacterial metabolite, is anti-malarial in vivo and nonmutagenic in vitro. J Nat Toxins, 2002, 11: 367-377.

[105.] Kim CH, Kim SW, Hong SI. An integrated fermentation–separation process for the production of red pigment by Serratia sp. KH-95. Process Biochem., 1999, 35(5): 485-90.

[106.] Woodhams DC, LaBumbard BC, Barnhart KL, Becker MH, Bletz MC, Escobar LA, Flechas SV, Forman ME, Iannetta AA, Joyce MD, Rabemananjara F, Gratwicke B, Vences M, Minbiole KPC. Prodigiosin, violacein, and volatile organic compounds produced by widespread cutaneous bacteria of amphibians can inhibit two batrachochytrium fungal pathogens. Microb Ecol, 2018, 75(4): 1049-1062.

[107.] Han SB, Park SH, Jeon YJ, Kim YK, Kim HM, Yang KH. Prodigiosin blocks T cell activation by inhibiting interleukin-2Rα expression and delays progression of autoimmune diabetes and collagen-induced arthritis. J Pharmacol Exp Ther, 2001, 299(2): 415-425.

[108.] Kumar A, Vishwakarma HS, Singh J, Dwivedi S, Kumar M. Microbial pigments: production and their applications in various industries. Int J Pharm Chem Biol Sci, 2015, 5:203-212.

[109.] Venil CK, Zakaria ZA, Ahmad WA. Bacterial pigments and their applications. Process Biochem, 2013, 48: 1065-1079.

[110.] Yusof NZ. Isolation and applications of red pigment from Serratia marcescens, 2008 Malaysia UniversitiTeknologi Malaysia

[111.] Venil CK, Dufossé L, Velmurugan P, Malathi M, Lakshmanaperumalsamy P. Extraction and application of pigment from Serratia marcescens SB08, an insect enteric gut bacterium, for textile dyeing. Textiles, 2021, 1: 3.

[112.] Ren Y, Gong J, Wang F, Li Z, Zhang J, Fu R, Lou J. Effect of dye bath pH on dyeing and functional properties of wool fabric dyed with tea extract. Dyes Pigm., 2016, 134: 334-341.

[113.] Ren Y, Gong J, Fu R, Zhang J, Fang K, Liu X. Antibacterial dyeing of silk with prodigiosinssuspention produced by liquid fermentation. J Clean Prod, 2018, 201: 648-656.

[114.] Metwally RA, El Sikaily A, El-Sersy NA, Ghozlan HA, Sabry SA. Antimicrobial activity of textile fabrics dyed with prodigiosin pigment extracted from marine Serratia rubidaea RAM_Alex bacteria. Egypt J Aquat Res, 2021, 47: 301-305.

[115.] Kramar AD, Ilic-Tomic TR, Lađarević JM, Nikodinovic-Runic JB, Kostic MM. Halochromic cellulose textile obtained via dyeing with biocolorant isolated from Streptomyces sp. strain NP4. Cellulose, 2021, 28: 8771-8784.

[116.] Ren Y, Gong J, Fu R, Li Z, Li Q, Zhang J, Yu Z, Cheng X. Dyeing and antibacterial properties of cotton dyed with prodigiosinsnanomicelles produced by microbial fermentation. Dyes Pigm, 2017, 138: 147-153.

[117.] Ryazantseva I, Andreyeva I. Application of prodigiosin as a colorant for polyolefines. Adv Biol Chem, 2014, 04: 20-25.

[118.] Krishna JG, Basheer SM, Beena PS, Chandrasekaran M. Marine bacteria as source of pigment for application as dye in textile industry. In: Proc Internatl Conf BiodivConservMgt, Vol. 1; 2008. p. 743–744.

[119.] Shirata A, Tsukamoto T, Yasui H, et al. Isolation of bacteria producing bluish–purple pigment and use for dyeing. Jpn Agric Res Q, 2000, 34(2): 131-140.

[120.] Ahmad WA, Wan Ahmad WY, Zakaria ZA, Yusof NZ, Ahmad WA, Ahmad WYW, Zakaria ZA, Yusof NZ. Application of bacterial pigments as colorant, 2012 Berlin Springer 57-74.

[121.] Mekhael RAMINA, Yousif SY. The role of red pigment produced by Serratia marcescens as antibacterial and plasmid curing agent. J Duhok Univ, 2009, 12(1): 268-274.

[122.] Huang CH, Pan JH, Chen B, Yu M, Huang HB, Zhu X, Lin YC. Three bianthraquinone derivatives from the mangrove endophytic fungus Alternaria sp. ZJ9–6B from the South China Sea. Mar Drugs, 2011, 9(5): 832-843.

[123.] Khanafari A, Assadi MM, Fakhr FA. Review of prodigiosin, pigmentation in Serratia marcescens Qods Sqr. Tajrish Sqr. Tehran, Iran Department of Forest Sciences, Faculty of Forestry, The University of British Columbia, 4th Floor Forest Sciences Centre; 2006. p 4320–4424.

[124.] Song Y, Liu G, Li J, Huang H, Zhang X, Zhang H, Ju J. Cytotoxic and antibacterial angucycline- and prodigiosinanalogues from the deep-sea derived Streptomyces sp. SCSIO 11594. Mar Drugs, 2015, 13: 1304-2131.

[125.] Sen T, Barrow CJ, Deshmukh SK. Microbial pigments in the food industry—challenges and the way forward. Front Nutr, 2019, 6: 7.

[126.] Lee JC, Kim Y-S, Park S, Kim J, Kang S-J, Lee M-H, Ryu S, Choi JM, Oh T-K, Yoon J-H. Exceptional production of both prodigiosin and cycloprodigiosin as major metabolic constituents by a novel marine bacterium, Zooshikella rubidus S1–1. Appl Environ Microbiol, 2011, 77: 4967-4973.

[127.] Gerber NN, Gauthier MJ. New prodigiosin-like pigment from Alteromonas rubra. Appl Environ Microbiol, 1979, 37(6): 1176-1179.

[128.] Kim D, Lee JS, Park YK, Kim JF, Jeong H, Oh TK, Kim BS, Lee CH. Biosynthesis of antibiotic prodiginines in the marine bacterium Hahella chejuensis KCTC 2396. J Appl Microbiol, 2007, 102(4): 937-944.

[129.] Yamamoto C, Takemoto H, Kuno K, Yamamoto D, Tsubura A, Kamata K, Hirata H, Yamamoto A, Kano H, Seki T, Inoue K. Cycloprodigiosin hydrochloride, a new H+/Cl− symporter, induces apoptosis in human and rat hepatocellular cancer cell lines in vitro and inhibits the growth of hepatocellular carcinoma xenografts in nude mice. Hepatology, 1999, 30(4): 894-902.

[130.] Kawauchi K, Shibutani K, Yagisawa H, Kamata H, Nakatsuji SI, Anzai H, Yokoyama Y, Ikegami Y, Moriyama Y, Hirata H. A possible immunosuppressant, cycloprodigiosin hydrochloride, obtained from Pseudoalteromonas denitrificans. Biochem Biophys Res Commun, 1997, 237(3): 543-547.

[131.] Metwally RA, Abeer A, El-Sikaily A, El-Sersy NA, Ghozlan H, Sabry S. Biological activity of prodigiosin from Serratia rubidaea RAM_Alex. Res J Biotechnol, 2019, 14:100

[132.] Setiyono E, Adhiwibawa MAS, Indrawati R, Prihastyanti MNU, Shioi Y, Brotosudarmo THP. An Indonesian marine bacterium, Pseudoalteromonas rubra, produces antimicrobial prodiginine pigments. ACS Omega, 2020, 5: 4626-4635.