Applied Microbiology and Biotechnology

, Volume 103, Issue 4, pp 1667–1680 | Cite as

Recent advancements in high-level synthesis of the promising clinical drug, prodigiosin

  • Chee-Hoo Yip
  • Orr Yarkoni
  • James Ajioka
  • Kiew-Lian Wan
  • Sheila NathanEmail author


Prodigiosin, a red linear tripyrrole pigment and a member of the prodiginine family, is normally secreted by the human pathogen Serratia marcescens as a secondary metabolite. Studies on prodigiosin have received renewed attention as a result of reported immunosuppressive, antimicrobial and anticancer properties. High-level synthesis of prodigiosin and the bioengineering of strains to synthesise useful prodiginine derivatives have also been a subject of investigation. To exploit the potential use of prodigiosin as a clinical drug targeting bacteria or as a dye for textiles, high-level synthesis of prodigiosin is a prerequisite. This review presents an overview on the biosynthesis of prodigiosin from its natural host Serratia marcescens and through recombinant approaches as well as highlighting the beneficial properties of prodigiosin. We also discuss the prospect of adopting a synthetic biology approach for safe and cost-effective production of prodigiosin in a more industrially compliant surrogate host.


Prodigiosin Beneficial secondary metabolite Gene cluster Bifurcated pathway High-level synthesis 


Funding information

We gratefully acknowledge Universiti Kebangsaan Malaysia for the funding provided (grant number ICONIC-2013-004) that initiated this collaboration and the Commonwealth Scholarship Commission for supporting C.H. Yip through the Commonwealth Split-Site PhD Award 2015 during his placement at Cambridge University.

Compliance with ethical standards

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Andreyeva IN, Ogorodnikova TI (2015) Pigmentation of Serratia marcescens and spectral properties of prodigiosin. Mikrobiologiia 84:43–49. Google Scholar
  2. Arivizhivendhan KV, Mahesh M, Boopathy R, Sekaran G (2016) A novel method for the extraction of prodigiosin from bacterial fermenter integrated with sequential batch extraction reactor using magnetic iron oxide. Process Biochem 51:1731–1737. Google Scholar
  3. Atsumi S, Hanai T, Liao JC (2008) Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Nature 451:86–89. Google Scholar
  4. Bae J, Moon H, Oh KK, Kim CH, Lee DS, Kim SW, Hong SI (2001) A novel bioreactor with an internal adsorbent for integrated fermentation and recovery of prodigiosin-like pigment produced from Serratia sp. KH-95. Biotechnol Lett 23:1315–1319. Google Scholar
  5. Campo P, Morata TC, Hong OS (2013) Chemical exposure and hearing loss. Dis Mon 59:119–138. Google Scholar
  6. Carbonell GV, Della Colleta HHM, Yano T, Darini ALC, Levy CE, Fonseca BAL (2000) Clinical relevance and virulence factors of pigmented Serratia marcescens. FEMS Immunol Med Microbiol 28:143–149. Google Scholar
  7. Castro AJ (1967) Antimalarial activity of prodigiosin. Nature 213:903–904. Google Scholar
  8. Casullo de Araújo HW, Fukushima K, Campos-Takaki GM (2010) Prodigiosin production by Serratia marcescens UCP 1549 using renewable-resources as low-cost substrate. Molecules 15:6931–6940. Google Scholar
  9. Chang MCY, Eachus RA, Trieu W, Ro DK, Keasling JD (2007) Engineering Escherichia coli for the production of functionalized terpenoids using plant P450s. Nat Chem Biol 3:274–277. Google Scholar
  10. Chang CC, Chen WC, Ho SF, Wu HS, Wei YH (2011) Development of natural anti-tumor drugs by microorganisms. J Biosci Bioeng 111:501–511. Google Scholar
  11. Chen WC, Yu WJ, Chang CC, Chang JS, Huang SH, Chang CH, Chen SY, Chien CC, Yao CL, Chen WM, Wei YH (2013) Enhancing production of prodigiosin from Serratia marcescens C3 by statistical experiment design and porous carrier addition strategy. Biochem Eng J 78:93–100. Google Scholar
  12. Chen WC, Tsai MJ, Soo PC, Wang LF, Tsai SL, Chang YK, Wei YH (2018) Construction and co-cultivation of two mutant strains harboring key precursor genes to produce prodigiosin. J Biosci Bioeng 126:783–789. Google Scholar
  13. Chiappori AA, Schreeder MT, Moezi MM, Stephenson JJ, Blakely J, Salgia R, Chu QS, Ross HJ (2012) A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer. Br J Cancer 106:839–845. Google Scholar
  14. Cunningham DS, Koepsel RR, Ataai M, Domach MM (2009) Factors affecting plasmid production in Escherichia coli from a resource allocation standpoint. Microb Cell Factories 8:27. Google Scholar
  15. Danevčič T, Vezjak MB, Zorec M, Stopar D (2016a) Prodigiosin-a multifaceted Escherichia coli antimicrobial agent. PLoS One 11.
  16. Danevčič T, Vezjak MB, Tabor M, Zorec M, Stopar D (2016b) Prodigiosin induces autolysins in actively grown Bacillus subtilis cells. Front Microbiol 7.
  17. Darshan N, Manonmani HK (2016) Prodigiosin inhibits motility and activates bacterial cell death revealing molecular biomarkers of programmed cell death. AMB Express 6:50. Google Scholar
  18. Dauenhauer SA, Hull RA, Williams RP (1984) Cloning and expression in Escherichia coli of Serratia marcescens genes encoding prodigiosin biosynthesis. J Bacteriol 158:1128–1132Google Scholar
  19. Davis JT (2010) Anion binding and transport by prodigiosin and its analog. In: Gale P, Dehaen W (eds) Anion recognition in supramolecular chemistry. Topics in heterocyclic chemistry, vol 24. Springer, Berlin, Heidelberg, pp 145–176Google Scholar
  20. Do HNA, Nguyen THK (2014) Studies on the prodigiosin production from Streptomyces coelicolor in liquid media by using heated Lactobacillus rhamnosus. J Appl Pharm Sci 4:21–24. Google Scholar
  21. Domrose A, Klein AS, Hage-Huismann J, Thies S, Svensson V, Classen T, Pietruszka J, Jaegar K, Drepper T, Loeschcke A (2015) Efficient recombinant production of prodigiosin in Pseudomonas putida. Front Microbiol 6.
  22. Dong T, Schellhorn HE (2010) Role of RpoS in virulence of pathogens. Infect Immun 78:887–897. Google Scholar
  23. Dozie-Nwachukwu SO, Danyuo Y, Obayemi JD, Odusanya OS, Malatesta K, Soboyejo WO (2017) Extraction and encapsulation of prodigiosin in chitosan microsphere for targeted drug delivery. Mater Sci Eng C 71:268–278. Google Scholar
  24. Drink E, Dugourd P, Dumont E, Aronssohn N, Antoine R, Loison C (2015) Optical properties of prodigiosin and obatoclax. Action spectroscopy and theorectical calculations. Phys Chem Chem Phys 17:25946–25955. Google Scholar
  25. Duzhak AB, Panfilova ZI, Duzhak TG, Vasyunina EA, Shternshis MV (2012) Role of prodigiosin and chitinases in antagonistic activity of the bacterium Serratia marcescens against the fungus Didymella applanata. Biochemistry 77:910–916. Google Scholar
  26. Elahian F, Moghimi B, Dinmohammadi F, Ghamghami M, Hamidi M, Mirzaei SA (2013) The anticancer agent prodigiosin is not a multidrug resistance protein substrate. DNA Cell Biol 32(3):90–97. Google Scholar
  27. El-Bialy HA, El-Nour SAA (2015) Physical and chemical stress on Serratia marcescens and studies on prodigiosin production. Ann Microbiol 65:59–68. Google Scholar
  28. Elkenawy NM, Yassin AS, Elhifnawy HN, Amin MA (2017) Optimization of prodigiosin production by Serratia marcescens using crude glycerol and enhancing production using gamma radiation. Biotechnol Rep 14:47–53. Google Scholar
  29. Engler C, Kandzia R, Marillonnet S (2008) A one pot, one step, precision cloning method with high throughput capability. PLoS One 3:e3647. Google Scholar
  30. Fender JE, Bender CM, Stella NA, Lahr RM, Kalivoda EJ, Shanks RMQ (2012) Serratia marcescens quinoprotein glucose dehydrogenase activity mediates acidification and inhibition of prodigiosin production by glucose. Appl Environ Microbiol 78:6225–6235. Google Scholar
  31. Feng J, Shi W, Zhang S, Zhang Y (2015) Identification of new compounds with high activity against stationary phase Borellia burgdorferi from the NCI compound collection. Emerg Microbes Infect 4:e31. Google Scholar
  32. Figueiredo AC, Barroso JG, Pedro LG, Scheffer JJC (2008) Factors affecting secondary metabolite production in plants: volatile components and essential oils. Flavour Fragr J 23:213–226. Google Scholar
  33. Garneau-Tsodikova S, Dorrestein P, Kelleher NL, Walsh CT (2006) Protein assembly line components in prodigiosin biosynthesis: characterization of PigA, G, H, I, J. J Am Chem Soc 128:12600–12601. Google Scholar
  34. Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA III, Smith HO (2009) Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 6:343–345. Google Scholar
  35. Giri AV, Anandkumar N, Muthukumaran G, Pennathur G (2004) A novel medium for the enhanced cell growth and production of prodigiosin from Serratia marcescens isolated from soil. BMC Microbiol 4:11. Google Scholar
  36. Gulani C, Bhattacharya S, Das A (2012) Assessment of process parameters influencing the enhanced production of prodigiosin from Serratia marcescens and evaluation of its antimicrobial, antioxidant and dyeing potential. Malays J Microbiol 8:116–122. Google Scholar
  37. Guryanov ID, Karamova NS, Yusupova DV, Gnezdilov OI, Koshkarova LA (2013) Bacterial pigment prodigiosin and its genotoxic effect. Bioorg Khim 39:106–111. Google Scholar
  38. Haddix PL, Werner TF (2000) Spectrophotometric assay of gene expression: Serratia marcescens pigmentation. Bioscene 26:3–13Google Scholar
  39. Harris APK, Williamson NR, Slater H, Cox A, Abbasi S, Foulds I, Simonsen HT, Leeper FJ, Salmond GP (2004) The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation. Microbiology 150:3547–3560. Google Scholar
  40. Haseloff J, Ajioka J (2009) Synthetic biology: history, challenges and prospects. J R Soc Interface 6:S389–S391. Google Scholar
  41. Heidari N, Hicks MA, Harada H (2010) GX15-070 (obatoclax) overcomes glucocorticoid resistance in acute lymphoblastic leukemia through induction of apoptosis and autophagy. Cell Death Dis 1:e76. Google Scholar
  42. Hong B, Prabhu VV, Zhang S, van den Heuvel AP, Dicker DT, Kopelovich L, El-Deiry WS (2014) Prodigiosin rescues deficient p53 signaling and anti-tumor effects via up-regulating p73 and disrupting its interaction with mutant p53. Cancer Res 74:1153–1165. Google Scholar
  43. Ibrahim D, Nazari TF, Kassim J, Lim SH (2014) Prodigiosin-an antibacterial red pigment produced by Serratia marcescens IBRL USM 84 associated with a marine sponge Xestospongia testudinaria. J Appl Pharm Sci 4:1–6. Google Scholar
  44. Jolicoeur B, Lubell WD (2008) Prodigiosin synthesis with electron rich 2,2′-bipyrroles. Can J Chem 86:213–218. Google Scholar
  45. Juang RS, Yeh CL (2014) Adsorptive recovery and purification of prodigiosin from methanol/water solutions of Serratia marcescens fermentation broth. Biotechnol Bioprocess Eng 19:159–168. Google Scholar
  46. Juhas M, Ajioka JW (2015a) Flagellar region 3b supports strong expression of integrated DNA and the highest chromosomal integration efficiency of the Escherichia coli flagellar regions. Microb Biotechnol 8:726–738. Google Scholar
  47. Juhas M, Ajioka JW (2015b) Identification and validation of novel chromosomal integration and expression loci in Escherichia coli flagellar region 1. PLoS One 10:e0123007. Google Scholar
  48. Juhas M, Ajioka JW (2016a) High molecular weight DNA assembly in vivo for synthetic biology applications. Crit Rev Biotechnol 37:277–286. Google Scholar
  49. Juhas M, Ajioka JW (2016b) Integrative bacterial artificial chromosomes for DNA integration into the Bacillus subtilis chromosome. J Microbiol Methods 125:1–7. Google Scholar
  50. Juhas M, Evans LDB, Frost J, Davenport PW, Yarkoni O, Gillian MF, Ajioka JW (2014) Escherichia coli flagellar genes as target sites for integration and expression of genetic circuits. PLoS One 9:e111451. Google Scholar
  51. Kamble KD, Hiwarale VD (2012) Prodigiosin production from Serratia marcescens strain obtained from farm soil. Int J Environ Sci 3:631–638. Google Scholar
  52. Kavitha R, Aiswariya S, Ratnavali CMG (2010) Anticancer activity of red pigment from Serratia marcescens in human cervix carcinoma. Int J Pharmtech Res 2:784–787Google Scholar
  53. Kawasaki T, Sakurai F, Hayakawa Y (2008) A prodigiosin from the roseophilin producer Streptomyces griseoviridis. J Nat Prod 71:1265–1267. Google Scholar
  54. Keasling JD (2008) Synthetic biology for synthetic chemistry. ACS Chem Biol 3:64–76. Google Scholar
  55. Khanam B, Chandra R (2018) Comparative analysis of prodigiosin isolated from endophyte Serratia marcescens. Lett Appl Microbiol 66:194–201. Google Scholar
  56. Kim D, Park YK, Lee JS, Kim JF, Jeong H, Kim BS, Lee CH (2006) Analysis of a prodigiosin biosynthetic gene cluster from the marine bacterium Hahella chejuensis KCTC 2396. J Microbiol Biotechnol 16:1912–1918Google Scholar
  57. Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, Han L, He J, He S, Shoemaker BA, Wang J, Yu B, Zhang J, Bryant SH (2016) PubChem substance and compound databases. Nucleic Acids Res 44:D1202–D1213. Google Scholar
  58. Kimyon O, Das T, Ibugo AI, Kutty SK, Ho KK, Tebben J, Kumar N, Manefield M (2016) Serratia secondary metabolite prodigiosin inhibits Pseudomonas aeruginosa biofilm development by producing reactive oxygen species that damage biological molecules. Front Microbiol 7.
  59. Kurbanoglu EB, Ozdal M, Ozdal OG, Algur OF (2015) Enhanced production of of prodigiosin by Serratia marcescens MO-1 using ram horne peptone. Braz J Microbiol 46:631–637. Google Scholar
  60. Kwon SK, Park YK, Kim JF (2010) Genome-wide screening and identification of factors affecting the biosynthesis of prodigiosin by Hahella chejuensis, using Escherichia coli as a surrogate host. Appl Environ Microbiol 76:1661–1668. Google Scholar
  61. Lapenda JC, Maciel CCS, Xavier HS, Alves da Silva CA, Campos-Takaki CM (2014) Production and toxicology evaluation of prodigiosin from Serratia marcescens UCP/WFCC1549 on mannitol solid medium. Int J Appl Res Nat Prod 7:32–38Google Scholar
  62. Lapenda JC, Silva PA, Vicalvi MC, Sena KXFR, Nascimento SC (2015) Antimicrobial activity of prodigiosin isolated from Serratia marcescens UFPEDA 398. World J Microbiol Biotechnol 31:399–406. Google Scholar
  63. Lee JS, Kim YS, Park S, Kim J, Kang SJ, Lee MH, Ryu S, Choi JM, Oh TK, Yoon JH (2011) Exceptional production of both prodigiosin and cycloprodigiosin as major metabolic constituents by a novel marine bacterium, Zooshikella rubidus S1-1. Appl Environ Microbiol 77:4967–4973. Google Scholar
  64. Li PP, Kwok AHY, Jiang JW, Ran TT, Xu DQ, Wang WW, Leung FC (2015) Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential. PLoS One 10.
  65. Liu GY, Nizet V (2009) Color me bad: microbial pigments as virulence factors. Trends Microbiol 17:406–413. Google Scholar
  66. Liu PP, Zhu H, Zheng GS, Jiang WH, Lu YH (2017) Metabolic engineering of Streptomyces coelicolor for enhanced prodigiosins (RED) production. Sci China Life Sci 60:948–957. Google Scholar
  67. Mahlen SD (2011) Serratia infections: from military experiments to current practice. Clin Microbiol Rev 24:755–791. Google Scholar
  68. Melvin MS, Tomlinson JT, Saluta GR, Kucera GL, Lindquist N, Manderville RA (2000) Double strand DNA cleavage by copper-prodigiosin. J Am Chem Soc 122:6333–6334. Google Scholar
  69. Montaner B, Navarro S, Piqué M, Vilaseca M, Martinell M, Giralt E, Gil J, Perez-Tomas P (2000) Prodigiosin from the supernatant of Serratia marcescens induces apoptosis in haematopoietic cancer cell lines. Br J Pharmacol 131:585–593. Google Scholar
  70. Nakashima T, Tamura T, Kurachi M, Yamaguchi K, Oda T (2005) Apoptosis-mediated cytotoxicity of prodigiosin-like red pigments produced by gamma-Proteobacterium and its multiple bioactivities. Biol Pharm Bull 28:2289–2295. Google Scholar
  71. Neidle S (2013) Prodigiosin. In: Neidle S (ed) Cancer drug design and discovery. School of Pharmacy, University College London, London, pp 104–105Google Scholar
  72. O’ Brien SM, Claxton DF, Crump M, Faderi S, Kipps T, Keating MJ, Viallet J, Cheson BD (2009) Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia. Blood 113:299–305. Google Scholar
  73. Pandey R, Chander R, Sainis KB (2009) Prodigiosins as anticancer agents: living upto their name. Curr Pharm Des 15:732–741. Google Scholar
  74. Papireddy K, Smilkstein M, Kelly JX, Salem SM, Alhamadsheh M, Haynes SW, Challis GL, Reynolds KA (2011) Antimalarial activity of natural and synthetic prodiginines. J Med Chem 54:5296–5306. Google Scholar
  75. Park G, Tomlinson JT, Melvin MS, Wright MW, Day CS, Manderville RA (2003) Zinc and copper complexes of prodigiosin: implications for copper-mediated double-strand DNA cleavage. Org Lett 5:113–116. Google Scholar
  76. Patil CD, Patil SV, Salunke BK, Salunkhe RB (2011) Prodigiosin produced by Serratia marcescens NMCC46 as a mosquito larvicidal agent against Aedes aegypti and Anopheles stephensi. Parasitol Res 109:1179–1187. Google Scholar
  77. Raj DN, Dhanasekaran D, Thajuddin N, Panneerselvam A (2009) Production of prodigiosin from Serratia marcescens and its cytotoxicity activity. J Pharm Res 2:590–593Google Scholar
  78. Ramani D, Nair A, Krithika K (2014) Optimization of cultural conditions for the production of prodigiosin by Serratia marcescens and screening of the antimicrobial activity of prodigiosin. Int J Pharm Bio Sci 5:383–392Google Scholar
  79. Roy P, Ahmed NH, Grover RK (2014) Non-pigmented strain of Serratia marcescens: an unusual pathogen causing pulmonary infection in a patient with malignancy. J Clin Diagn Res 8:DD05–DD06. Google Scholar
  80. Seah SW, Nathan S, Wan KL (2016) Toxicity evaluation of prodigiosin from Serratia marcescens in a Caenorhabditis elegans model. AIP Conf Proc 1784:020015. Google Scholar
  81. Seganish JL, Davis JT (2005) Prodigiosin is a chloride carrier that can function as an anion exchanger. Chem Commun (Camb) 46:5781–5783. Google Scholar
  82. Shaikh Z (2016) Biosynthesis of prodigiosin and its applications. IOSR J Pharm Biol Sci 11:1–28. Google Scholar
  83. Siva R, Subha K, Bhakta Ghosh AR, Babu S (2011) Characterization and enhanced production of prodigiosin from the spoiled coconut. Appl Biochem Biotechnol 166:187–196. Google Scholar
  84. Solovyev V, Salamov A (2011) Automatic annotation of microbial genomes and metagenomic sequences. In: Li RW (ed) Metagenomics and its applications in agriculture, biomedicine and environmental studies. Nova Science Publishers, New York, pp 61–78Google Scholar
  85. Song MJ, Bae J, Lee DS, Kim CH, Kim JS, Kim SW, Hong SI (2006) Purification and characterization of prodigiosin produced by integrated bioreactor from Serratia sp. KH-95. J Biosci Bioeng 101:157–161. Google Scholar
  86. Soto-Cerrato V, Vinals F, Lambert JR, Perez-Tomas R (2007) The anticancer prodigiosin induces p21WAF1/CIP1 expression via transforming growth factor-beta receptor pathway. Biochem Pharmacol 74:1340–1349. Google Scholar
  87. Spiteller P, Kern W, Reiner J, Spiteller G (2001) Aldehydic lipid peroxidation products derived from linoleic acid. Biochim Biophys Acta 1531:188–208. Google Scholar
  88. Stankovic N, Senerovic L, Ilic-Tomic T, Vasiljevic B, Nikodinovic-Runic J (2014) Properties and applications of undecylprodigiosin and other bacterial prodigiosins. Appl Microbiol Biotechnol 98:3841–3858. Google Scholar
  89. Sumathi C, MohanaPriya D, Swarnalatha S, Dinesh MG, Sekaran G (2014) Production of prodigiosin using tannery fleshing and evaluating its pharmacological effects. ScientificWorldJournal 2014:1–8. Google Scholar
  90. Sun SQ, Wang YJ, Xu W, Zhu CJ, Liu XX (2015) Optimizing ultrasound-assisted extraction of prodigiosin by response surface methodology. Prep Biochem Biotechnol 45:101–108. Google Scholar
  91. Suryawanshi RK, Patil CD, Koli SH, Hallsworth JE, Patil SV (2016) Antimicrobial activity of prodigiosin is attributed to plasma-membrane damage. Nat Prod Res 31:572–577. Google Scholar
  92. Urtishak KA, Edwards AY, Wang LS, Hudome A, Robinson BW, Barrett JS, Cao K, Cory L, Moore JS, Bantly AD, Yu QC, Chen IM, Atlas SR, Willman CL, Kundu M, Carroll AJ, Heerema NA, Devidas M, Hilden JM, Dreyer ZE, Hunger SP, Reaman GH, Felix CA (2013) Potent obatoclax cytotoxicity and activation of triple death mode killing across infant acute lymphoblastic leukemia. Blood 121:2689–2703. Google Scholar
  93. Venil CK, Velmurugam P, Lakshmanaperumalsamy P (2009) Genomic environment of cueR and copA genes for prodigiosin biosynthesis by Serratia marcescens SB08. Rom Biotechnol Lett 14:4812–4819Google Scholar
  94. Wang B, Lin L, Lu L, Chen W (2012a) Optimization of β-carotene production by newly isolated Serratia marcescens strain. Electron J Biotechnol 15.
  95. Wang SL, Wang CY, Yen YH, Liang TW, Chen SY, Chen CH (2012b) Enhanced production of insecticidal prodigiosin from Serratia marcescens TKU011 in media containing squid pen. Process Biochem 47:1684–1690. Google Scholar
  96. Wang F, Luo HL, Song GH, Liu C, Wang JG, Xu JL, Su XH, Ma XY (2013) Prodigiosin found in Serratia marcescens y2 initiates phototoxicity in the cytomembrane. Electron J Biotechnol 16.
  97. Wilft NM, Salmond GPC (2012) The stationary phase sigma factor, RpoS, regulates the production of a carbapenem antibiotic, a bioactive prodigiosin and virulence in the enterobacterial pathogen Serratia sp. ATCC 39006. Microbiology 158:648–658. Google Scholar
  98. Williamson NR, Simonsen HT, Ahmed RAA, Goldet G, Slater H, Woodley L, Leeper FJ, Salmond GP (2005) 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 56:971–989. Google Scholar
  99. Williamson NR, Fineran PC, Leeper FJ, Salmond GPC (2006a) The biosynthesis and regulation of bacterial prodiginines. Nat Rev Microbiol 4:887–899. Google Scholar
  100. Williamson NR, Simonsen HT, Harris AKP, Leeper FJ, Salmond GPC (2006b) Disruption of the copper efflux pump (CopA) of Serratia marcescens ATCC 274 pleiotropically affects copper sensitivity and production of the tripyrrole secondary metabolite, prodigiosin. J Ind Microbiol Biotechnol 33:151–158. Google Scholar
  101. Yip CH, Yarkoni O, Ajioka J, Wan KL, Nathan S (2018) Development of a codon optimization strategy using the eforRED reporter gene as a test case. AIP Conf Proc 1940:020080. Google Scholar
  102. Yip CH, Yarkoni O, Mario J, Ajioka J, Wan KL, Nathan S (in press) The Escherichia coli motA flagellar gene as a potential integration site for large synthetic DNA. Sains MalaysGoogle Scholar
  103. You ZY, Zhang SP, Liu XX, Wang YJ (2018) Enhancement of prodigiosin synthetase (PigC) production from recombinant Escherichia coli through optimization of induction strategy and media. Prep Biochem Biotechnol 48:226–233. Google Scholar
  104. Zhang B, Zhang L, Dai RX, Yu MY, Zhao GP, Ding XM (2013) An efficient procedure for marker-free mutagenesis of S. coelicolor by site-specific recombination for secondary metabolite overproduction. PLoS One 8:e55906. Google Scholar
  105. Zhou W, Li JH, Chen J, Liu XY, Xiang TT, Zhang L, Wan YJ (2016) The red pigment prodigiosin is not an essential virulence factor in entomopathogenic Serratia marcescens. J Invertebr Pathol 136:92–94. Google Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Biosciences and Biotechnology, Faculty of Science and TechnologyUniversiti Kebangsaan MalaysiaBangiMalaysia
  2. 2.Department of PathologyUniversity of CambridgeCambridgeUK

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