Applied Microbiology and Biotechnology

, Volume 98, Issue 10, pp 4355–4368 | Cite as

Metabolic engineering for the microbial production of carotenoids and related products with a focus on the rare C50 carotenoids

  • Sabine A. E. Heider
  • Petra Peters-Wendisch
  • Volker F. Wendisch
  • Jules Beekwilder
  • Trygve Brautaset


Carotenoids, a subfamily of terpenoids, are yellow- to red-colored pigments synthesized by plants, fungi, algae, and bacteria. They are ubiquitous in nature and take over crucial roles in many biological processes as for example photosynthesis, vision, and the quenching of free radicals and singlet oxygen. Due to their color and their potential beneficial effects on human health, carotenoids receive increasing attention. Carotenoids can be classified due to the length of their carbon backbone. Most carotenoids have a C40 backbone, but also C30 and C50 carotenoids are known. All carotenoids are derived from isopentenyl pyrophosphate (IPP) as a common precursor. Pathways leading to IPP as well as metabolic engineering of IPP synthesis and C40 carotenoid production have been reviewed expertly elsewhere. Since C50 carotenoids are synthesized from the C40 carotenoid lycopene, we will summarize common strategies for optimizing lycopene production and we will focus our review on the characteristics, biosynthesis, glycosylation, and overproduction of C50 carotenoids.


Metabolic engineering of carotenoids C50 carotenoids Lycopene elongase C50 carotenoid cyclase C50 carotenoid glucosyltransferase 



SAEH, PPW and VFW acknowledge the support in part by grants from BMBF project 0316017A and from EU project PROMYSE. JB acknowledges the “Platform Green Synthetic Biology” program ( funded by the Netherlands Genomics Initiative for financial support. TB acknowledges the support in part by EU project PROMYSE.


  1. Abbes M, Baati H, Guermazi S, Messina C, Santulli A, Gharsallah N, Ammar E (2013) Biological properties of carotenoids extracted from Halobacterium halobium isolated from a Tunisian solar saltern. BMC Complement Alternat Med 13:255. doi: 10.1186/1472-6882-13-255 Google Scholar
  2. Alper H, Miyaoku K, Stephanopoulos G (2006) Characterization of lycopene-overproducing E. coli strains in high cell density fermentations. Appl Microbiol Biotechnol 72(5):968–974. doi: 10.1007/s00253-006-0357-y PubMedGoogle Scholar
  3. Andrewes AG, Starr MP (1976) (3R,3′R)-astaxanthin from the yeast Phaffia rhodozyma. Phytochemistry 15(6):1009–1011. doi: 10.1016/S0031-9422(00)84391-5 Google Scholar
  4. Araya-Garay JM, Ageitos JM, Vallejo JA, Veiga-Crespo P, Sanchez-Perez A, Villa TG (2012) Construction of a novel Pichia pastoris strain for production of xanthophylls. AMB Express 2(1):24. doi: 10.1186/2191-0855-2-24 PubMedCentralPubMedGoogle Scholar
  5. Armstrong GA (1994) Eubacteria show their true colors: genetics of carotenoid pigment biosynthesis from microbes to plants. J Bacteriol 176(16):4795–4802PubMedCentralPubMedGoogle Scholar
  6. Armstrong GA, Hearst JE (1996) Carotenoids 2: genetics and molecular biology of carotenoid pigment biosynthesis. FASEB J 10(2):228–237PubMedGoogle Scholar
  7. Arpin N, Liaaen-Jensen S, Trouilloud M (1972) Bacterial carotenoids. 38. C50-carotenoids. 9. Isolation of decaprenoxanthin mono- and diglucoside from an Arthrobacter sp. Acta Chem Scand 26(6):2524–2526PubMedGoogle Scholar
  8. Aschoff S (1818) Beiträge zur Kenntnis des Saffrans. Berl Jb Pharm 19:142–157Google Scholar
  9. Bari R, Jones JD (2009) Role of plant hormones in plant defence responses. Plant Mol Biol 69(4):473–488. doi: 10.1007/s11103-008-9435-0 PubMedGoogle Scholar
  10. Beekwilder J, van der Meer IM, Simic A, Uitdewilligen J, van Arkel J, de Vos RC, Jonker H, Verstappen FW, Bouwmeester HJ, Sibbesen O, Qvist I, Mikkelsen JD, Hall RD (2008) Metabolism of carotenoids and apocarotenoids during ripening of raspberry fruit. Biofactors 34(1):57–66PubMedGoogle Scholar
  11. Beuttler H, Hoffmann J, Jeske M, Hauer B, Schmid RD, Altenbuchner J, Urlacher VB (2011) Biosynthesis of zeaxanthin in recombinant Pseudomonas putida. Appl Microbiol Biotechnol 89(4):1137–1147. doi: 10.1007/s00253-010-2961-0 PubMedGoogle Scholar
  12. Bhosale P, Bernstein PS (2005) Microbial xanthophylls. Appl Microbiol Biotechnol 68(4):445–455. doi: 10.1007/s00253-005-0032-8 PubMedGoogle Scholar
  13. Boussiba S, Vonshak A, Cohen Z, Richmond A (2000) Procedure for large-scale production of astaxanthin from Haematococcus. US Patent 6022701Google Scholar
  14. Bouvier F, Dogbo O, Camara B (2003) Biosynthesis of the food and cosmetic plant pigment bixin (annatto). Science 300(5628):2089–2091. doi: 10.1126/science.1085162300/5628/2089 PubMedGoogle Scholar
  15. Brandi F, Bar E, Mourgues F, Horvath G, Turcsi E, Giuliano G, Liverani A, Tartarini S, Lewinsohn E, Rosati C (2011) Study of ‘Redhaven’ peach and its white-fleshed mutant suggests a key role of CCD4 carotenoid dioxygenase in carotenoid and norisoprenoid volatile metabolism. BMC Plant Biol 11:24. doi: 10.1186/1471-2229-11-24 PubMedCentralPubMedGoogle Scholar
  16. Britton G (2008) Functions of intact carotenoids. In: Britton, Liaaen-Jensen, Pfander (eds) Carotenoids: natural functions, vol 4. Birkhäuser Verlag, Basel, pp 189–212Google Scholar
  17. Chae HS, Kim KH, Kim SC, Lee PC (2010) Strain-dependent carotenoid productions in metabolically engineered Escherichia coli. Appl Biochem Biotechnol 162(8):2333–2344. doi: 10.1007/s12010-010-9006-0 PubMedGoogle Scholar
  18. Chen YY, Shen HJ, Cui YY, Chen SG, Weng ZM, Zhao M, Liu JZ (2013) Chromosomal evolution of Escherichia coli for the efficient production of lycopene. BMC Biotechnol 13:6. doi: 10.1186/1472-6750-13-6 PubMedCentralPubMedGoogle Scholar
  19. Cheng X, Ruyter-Spira C, Bouwmeester H (2013) The interaction between strigolactones and other plant hormones in the regulation of plant development. Front Plant Sci 4:199. doi: 10.3389/fpls.2013.00199 PubMedCentralPubMedGoogle Scholar
  20. Chumpolkulwong N, Kakizono T, Handa T, Nishio N (1997) Isolation and characterization of compactin resistant mutants of an astaxanthin synthesizing green alga Haematococcus pluvialis. Biotechnol Lett 19(3):299–302. doi: 10.1023/A:1018330329357 Google Scholar
  21. Cooper DA, Eldridge AL, Peters JC (1999) Dietary carotenoids and certain cancers, heart disease, and age-related macular degeneration: a review of recent research. Nutr Rev 57(7):201–214PubMedGoogle Scholar
  22. Coutinho PM, Deleury E, Davies GJ, Henrissat B (2003) An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 328(2):307–317PubMedGoogle Scholar
  23. Cutzu R, Coi A, Rosso F, Bardi L, Ciani M, Budroni M, Zara G, Zara S, Mannazzu I (2013) From crude glycerol to carotenoids by using a Rhodotorula glutinis mutant. World J Microbiol Biotechnol 29(6):1009–1017. doi: 10.1007/s11274-013-1264-x PubMedGoogle Scholar
  24. Das A, Yoon SH, Lee SH, Kim JY, Oh DK, Kim SW (2007) An update on microbial carotenoid production: application of recent metabolic engineering tools. Appl Microbiol Biotechnol 77(3):505–512. doi: 10.1007/s00253-007-1206-3 PubMedGoogle Scholar
  25. Daum M, Herrmann S, Wilkinson B, Bechthold A (2009) Genes and enzymes involved in bacterial isoprenoid biosynthesis. Curr Opin Chem Biol 13(2):180–188. doi: 10.1016/j.cbpa.2009.02.029 PubMedGoogle Scholar
  26. de Bont J (1998) Solvent-tolerant bacteria in biocatalysis. Trends Biotechnol 16(12):493–499. doi: 10.1016/S0167-7799(98)01234-7 Google Scholar
  27. De Roos AL, van Dijk AA, Folkertsma B (2005) Bleaching of dairy products. International Patent WO 2005/004616Google Scholar
  28. Dembitsky VM (2005) Astonishing diversity of natural surfactants: 3. Carotenoid glycosides and isoprenoid glycolipids. Lipids 40(6):535–557PubMedGoogle Scholar
  29. Downham A, Collins P (2000) Colouring our foods in the last and next millennium. Int J Food Sci Tech 35(1):5–22. doi: 10.1046/j.1365-2621.2000.00373.x Google Scholar
  30. Fukuoka S, Ajiki Y, Ohga T, Kawanami Y, Izumori K (2004) Production of dihydroxy C50-carotenoid by Aureobacterium sp. FERM P-18698. Biosci Biotechnol Biochem 68(12):2646–2648PubMedGoogle Scholar
  31. Gassel S, Schewe H, Schmidt I, Schrader J, Sandmann G (2013) Multiple improvement of astaxanthin biosynthesis in Xanthophyllomyces dendrorhous by a combination of conventional mutagenesis and metabolic pathway engineering. Biotechnol Lett 35(4):565–569. doi: 10.1007/s10529-012-1103-4 PubMedGoogle Scholar
  32. Gopinath V, Meiswinkel TM, Wendisch VF, Nampoothiri KM (2011) Amino acid production from rice straw and wheat bran hydrolysates by recombinant pentose-utilizing Corynebacterium glutamicum. Appl Microbiol Biotechnol 92(5):985–996. doi: 10.1007/s00253-011-3478-x PubMedGoogle Scholar
  33. Graham JE, Bryant DA (2009) The biosynthetic pathway for myxol-2′ fucoside (myxoxanthophyll) in the cyanobacterium Synechococcus sp. strain PCC 7002. J Bacteriol 191(10):3292–3300. doi: 10.1128/JB.00050-09 PubMedCentralPubMedGoogle Scholar
  34. Harada H, Misawa N (2009) Novel approaches and achievements in biosynthesis of functional isoprenoids in Escherichia coli. Appl Microbiol Biotechnol 84(6):1021–1031. doi: 10.1007/s00253-009-2166-6 PubMedGoogle Scholar
  35. Havaux M (2013) Carotenoid oxidation products as stress signals in plants. Plant J. doi: 10.1111/tpj.12386 PubMedGoogle Scholar
  36. Heider SA, Peters-Wendisch P, Wendisch VF (2012) Carotenoid biosynthesis and overproduction in Corynebacterium glutamicum. BMC Microbiol 12(1):198. doi: 10.1186/1471-2180-12-198 PubMedCentralPubMedGoogle Scholar
  37. Heider SA, Peters-Wendisch P, Netzer R, Stafnes M, Brautaset T, Wendisch VF (2013) Production and glucosylation of C40 and C50 carotenoids by metabolically engineered Corynebacterium glutamicum. Appl Microbiol Biotechnol. doi: 10.1007/s00253-013-5359-y PubMedGoogle Scholar
  38. Hess BM, Xue J, Markillie LM, Taylor RC, Wiley HS, Ahring BK, Linggi B (2013) Coregulation of terpenoid pathway genes and prediction of isoprene production in using transcriptomics. PLoS One 8(6):e66104. doi: 10.1371/journal.pone.0066104 PubMedCentralPubMedGoogle Scholar
  39. Hundle BS, O'Brien DA, Alberti M, Beyer P, Hearst JE (1992) Functional expression of zeaxanthin glucosyltransferase from Erwinia herbicola and a proposed uridine diphosphate binding site. Proc Natl Acad Sci U S A 89(19):9321–9325PubMedCentralPubMedGoogle Scholar
  40. Jackson H, Braun CL, Ernst H (2008) The chemistry of novel xanthophyll carotenoids. Am J Cardiol 101(10A):50D–57D. doi: 10.1016/j.amjcard.2008.02.008 PubMedGoogle Scholar
  41. Johnson EA, Schroeder WA (1996) Microbial carotenoids. Adv Biochem Eng Biotechnol 53:119–178PubMedGoogle Scholar
  42. Julsing MK, Rijpkema M, Woerdenbag HJ, Quax WJ, Kayser O (2007) Functional analysis of genes involved in the biosynthesis of isoprene in Bacillus subtilis. Appl Microbiol Biotechnol 75(6):1377–1384. doi: 10.1007/s00253-007-0953-5 PubMedCentralPubMedGoogle Scholar
  43. Kelly M, Jensen SL (1967) Bacterial carotenoids. 26. C50-carotenoids. 2. Bacterioruberin. Acta Chem Scand 21(9):2578PubMedGoogle Scholar
  44. Kim SH, Park YH, Schmidt-Dannert C, Lee PC (2010) Redesign, reconstruction, and directed extension of the Brevibacterium linens C40 carotenoid pathway in Escherichia coli. Appl Environ Microbiol 76(15):5199–5206. doi: 10.1128/AEM.00263-10 PubMedCentralPubMedGoogle Scholar
  45. Kirby J, Keasling JD (2009) Biosynthesis of plant isoprenoids: perspectives for microbial engineering. Annu Rev Plant Biol 60:335–355. doi: 10.1146/annurev.arplant.043008.091955 PubMedGoogle Scholar
  46. Krinsky NI, Johnson EJ (2005) Carotenoid actions and their relation to health and disease. Mol Asp Med 26(6):459–516. doi: 10.1016/j.mam.2005.10.001 Google Scholar
  47. Krubasik P, Kobayashi M, Sandmann G (2001a) Expression and functional analysis of a gene cluster involved in the synthesis of decaprenoxanthin reveals the mechanisms for C50 carotenoid formation. Eur J Biochem 268(13):3702–3708PubMedGoogle Scholar
  48. Krubasik P, Takaichi S, Maoka T, Kobayashi M, Masamoto K, Sandmann G (2001b) Detailed biosynthetic pathway to decaprenoxanthin diglucoside in Corynebacterium glutamicum and identification of novel intermediates. Arch Microbiol 176(3):217–223PubMedGoogle Scholar
  49. Lale R, Berg L, Stuttgen F, Netzer R, Stafsnes M, Brautaset T, Vee Aune TE, Valla S (2011) Continuous control of the flow in biochemical pathways through 5′ untranslated region sequence modifications in mRNA expressed from the broad-host-range promoter Pm. Appl Environ Microbiol 77(8):2648–2655. doi: 10.1128/AEM.02091-10 PubMedCentralPubMedGoogle Scholar
  50. Lange N, Steinbüchel A (2011) beta-Carotene production by Saccharomyces cerevisiae with regard to plasmid stability and culture media. Appl Microbiol Biotechnol 91(6):1611–1622. doi: 10.1007/s00253-011-3315-2 PubMedGoogle Scholar
  51. Lange BM, Rujan T, Martin W, Croteau R (2000) Isoprenoid biosynthesis: the evolution of two ancient and distinct pathways across genomes. Proc Natl Acad Sci U S A 97(24):13172–13177PubMedCentralPubMedGoogle Scholar
  52. Lee PC, Schmidt-Dannert C (2002) Metabolic engineering towards biotechnological production of carotenoids in microorganisms. Appl Microbiol Biotechnol 60(1–2):1–11. doi: 10.1007/s00253-002-1101-x PubMedGoogle Scholar
  53. Li J, Zhu D, Niu J, Shen S, Wang G (2011) An economic assessment of astaxanthin production by large scale cultivation of Haematococcus pluvialis. Biotechnol Adv 29(6):568–574. doi: 10.1016/j.biotechadv.2011.04.001 PubMedGoogle Scholar
  54. Liaaen-Jensen S, Hertzberg S, Weeks OB, Schwieter U (1968) Bacterial carotenoids XXVII. C50-carotenoids. 3. Structure determination of dehydrogenans-P439. Acta Chem Scand 22(4):1171–1186PubMedGoogle Scholar
  55. Maresca JA, Bryant DA (2006) Two genes encoding new carotenoid-modifying enzymes in the green sulfur bacterium Chlorobium tepidum. J Bacteriol 188(17):6217–6223. doi: 10.1128/JB.00766-06 PubMedCentralPubMedGoogle Scholar
  56. Margalith PZ (1999) Production of ketocarotenoids by microalgae. Appl Microbiol Biotechnol 51(4):431–438PubMedGoogle Scholar
  57. Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat Biotechnol 21(7):796–802PubMedGoogle Scholar
  58. Meijnen JP, Verhoef S, Briedjlal AA, de Winde JH, Ruijssenaars HJ (2011) Improved p-hydroxybenzoate production by engineered Pseudomonas putida S12 by using a mixed-substrate feeding strategy. Appl Microbiol Biotechnol 90(3):885–893. doi: 10.1007/s00253-011-3089-6 PubMedCentralPubMedGoogle Scholar
  59. Meiswinkel TM, Rittmann D, Lindner SN, Wendisch VF (2013) Crude glycerol-based production of amino acids and putrescine by Corynebacterium glutamicum. Bioresour Technol. doi: 10.1016/j.biortech.2013.02.053 PubMedGoogle Scholar
  60. Miki W, Otaki N, Yokoyama A, Izumida H, Shimidzu N (1994) Okadaxanthin, a novel C50-narotenoid from a bacterium, Pseudomonas sp. KK10206c associated with marine sponge, Halichondria okadai. Experientia 50(7):684–686. doi: 10.1007/Bf01952874 Google Scholar
  61. Miller NJ, Sampson J, Candeias LP, Bramley PM, Rice-Evans CA (1996) Antioxidant activities of carotenes and xanthophylls. FEBS Lett 384(3):240–242PubMedGoogle Scholar
  62. Misawa N, Nakagawa M, Kobayashi K, Yamano S, Izawa Y, Nakamura K, Harashima K (1990) Elucidation of the Erwinia uredovora carotenoid biosynthetic pathway by functional analysis of gene products expressed in Escherichia coli. J Bacteriol 172(12):6704–6712PubMedCentralPubMedGoogle Scholar
  63. Miura Y, Kondo K, Saito T, Shimada H, Fraser PD, Misawa N (1998) Production of the carotenoids lycopene, beta-carotene, and astaxanthin in the food yeast Candida utilis. Appl Environ Microbiol 64(4):1226–1229PubMedCentralPubMedGoogle Scholar
  64. Naguib YM (2000) Antioxidant activities of astaxanthin and related carotenoids. J Agric Food Chem 48(4):1150–1154PubMedGoogle Scholar
  65. Netzer R, Stafsnes MH, Andreassen T, Goksoyr A, Bruheim P, Brautaset T (2010) Biosynthetic pathway for gamma-cyclic sarcinaxanthin in Micrococcus luteus: heterologous expression and evidence for diverse and multiple catalytic functions of C(50) carotenoid cyclases. J Bacteriol 192(21):5688–5699. doi: 10.1128/JB.00724-10 PubMedCentralPubMedGoogle Scholar
  66. Nishizaki T, Tsuge K, Itaya M, Doi N, Yanagawa H (2007) Metabolic engineering of carotenoid biosynthesis in Escherichia coli by ordered gene assembly in Bacillus subtilis. Appl Environ Microbiol 73(4):1355–1361. doi: 10.1128/AEM.02268-06 PubMedCentralPubMedGoogle Scholar
  67. Norgård S, Aasen AJ, Liaaen-Jensen S (1970) Bacterial carotenoids. 32. C50-carotenoids 6. Carotenoids from Corynebacterium poinsettiae including four new C50-diols. Acta Chem Scand 24(6):2183–2197PubMedGoogle Scholar
  68. Olson JA (1993) Molecular actions of carotenoids. Ann N Y Acad Sci 691:156–166PubMedGoogle Scholar
  69. Osawa A, Ishii Y, Sasamura N, Morita M, Kasai H, Maoka T, Shindo K (2010) Characterization and antioxidative activities of rare C(50) carotenoids-sarcinaxanthin, sarcinaxanthin monoglucoside, and sarcinaxanthin diglucoside-obtained from Micrococcus yunnanensis. J Oleo Sci 59(12):653–659PubMedGoogle Scholar
  70. Papagianni M (2012) Recent advances in engineering the central carbon metabolism of industrially important bacteria. Microb Cell Fact 11:50. doi: 10.1186/1475-2859-11-50 PubMedCentralPubMedGoogle Scholar
  71. Papp T, Velayos A, Bartok T, Eslava AP, Vagvolgyi C, Iturriaga EA (2006) Heterologous expression of astaxanthin biosynthesis genes in Mucor circinelloides. Appl Microbiol Biotechnol 69(5):526–531. doi: 10.1007/s00253-005-0026-6 PubMedGoogle Scholar
  72. Pfander H (1994) C-45-carotenoids and C-50-carotenoids. Pure Appl Chem 66(10–11):2369–2374. doi: 10.1351/pac199466102369 Google Scholar
  73. Pinnola A, Dall’Osto L, Gerotto C, Morosinotto T, Bassi R, Alboresi A (2013) Zeaxanthin binds to light-harvesting complex stress-related protein to enhance nonphotochemical quenching in Physcomitrella patens. Plant Cell 25(9):3519–3534. doi: 10.1105/tpc.113.114538 PubMedGoogle Scholar
  74. Quinones MA, Zeiger E (1994) A putative role of the xanthophyll, zeaxanthin, in blue light photoreception of corn coleoptiles. Science 264(5158):558–561. doi: 10.1126/science.264.5158.558 Google Scholar
  75. Rodrigues E, Mariutti LR, Mercadante AZ (2012) Scavenging capacity of marine carotenoids against reactive oxygen and nitrogen species in a membrane-mimicking system. Mar Drugs 10(8):1784–1798. doi: 10.3390/md10081784 PubMedCentralPubMedGoogle Scholar
  76. Rodriguez-Saiz M, de la Fuente JL, Barredo JL (2010) Xanthophyllomyces dendrorhous for the industrial production of astaxanthin. Appl Microbiol Biotechnol 88(3):645–658. doi: 10.1007/s00253-010-2814-x PubMedGoogle Scholar
  77. Rodriguez-Villalon A, Perez-Gil J, Rodriguez-Concepcion M (2008) Carotenoid accumulation in bacteria with enhanced supply of isoprenoid precursors by upregulation of exogenous or endogenous pathways. J Biotechnol 135(1):78–84. doi: 10.1016/j.jbiotec.2008.02.023 PubMedGoogle Scholar
  78. Rohmer M (1999) The discovery of a mevalonate-independent pathway for isoprenoid biosynthesis in bacteria, algae and higher plants. Nat Prod Rep 16(5):565–574PubMedGoogle Scholar
  79. Rohmer M, Bouvier P, Ourisson G (1979) Molecular evolution of biomembranes: structural equivalents and phylogenetic precursors of sterols. Proc Natl Acad Sci U S A 76(2):847–851PubMedCentralPubMedGoogle Scholar
  80. Rottem S, Markowitz O (1979) Carotenoids acts as reinforcers of the Acholeplasma laidlawii lipid bilayer. J Bacteriol 140(3):944–948PubMedCentralPubMedGoogle Scholar
  81. Saelices L, Youssar L, Holdermann I, Al-Babili S, Avalos J (2007) Identification of the gene responsible for torulene cleavage in the Neurospora carotenoid pathway. Mol Genet Genomics 278(5):527–537. doi: 10.1007/s00438-007-0269-2 PubMedGoogle Scholar
  82. Sandmann G (2001) Carotenoid biosynthesis and biotechnological application. Arch Biochem Biophys 385(1):4–12. doi: 10.1006/abbi.2000.2170 PubMedGoogle Scholar
  83. Scalcinati G, Partow S, Siewers V, Schalk M, Daviet L, Nielsen J (2012) Combined metabolic engineering of precursor and co-factor supply to increase alpha-santalene production by Saccharomyces cerevisiae. Microb Cell Fact 11:117. doi: 10.1186/1475-2859-11-117 PubMedCentralPubMedGoogle Scholar
  84. Schwartz SH, Tan BC, Gage DA, Zeevaart JA, McCarty DR (1997) Specific oxidative cleavage of carotenoids by VP14 of maize. Science 276(5320):1872–1874PubMedGoogle Scholar
  85. Sedkova N, Tao L, Rouviere PE, Cheng Q (2005) Diversity of carotenoid synthesis gene clusters from environmental Enterobactetiaceae strains. Appl Environ Microbiol 71(12):8141–8146. doi: 10.1128/aem.71.12.8141-8146.2005 PubMedCentralPubMedGoogle Scholar
  86. Seibold G, Auchter M, Berens S, Kalinowski J, Eikmanns BJ (2006) Utilization of soluble starch by a recombinant Corynebacterium glutamicum strain: growth and lysine production. J Biotechnol 124(2):381–391. doi: 10.1016/j.jbiotec.2005.12.027 PubMedGoogle Scholar
  87. Sivy TL, Fall R, Rosenstiel TN (2011) Evidence of isoprenoid precursor toxicity in Bacillus subtilis. Biosci Biotechnol Biochem 75(12):2376–2383PubMedGoogle Scholar
  88. Song GH, Kim SH, Choi BH, Han SJ, Lee PC (2013) Heterologous carotenoid-biosynthetic enzymes: functional complementation and effects on carotenoid profiles in Escherichia coli. Appl Environ Microbiol 79(2):610–618. doi: 10.1128/AEM.02556-12 PubMedCentralPubMedGoogle Scholar
  89. Steinbrenner J, Sandmann G (2006) Transformation of the green alga Haematococcus pluvialis with a phytoene desaturase for accelerated astaxanthin biosynthesis. Appl Environ Microbiol 72(12):7477–7484. doi: 10.1128/AEM.01461-06 PubMedCentralPubMedGoogle Scholar
  90. Sui X, Kiser PD, Lintig J, Palczewski K (2013) Structural basis of carotenoid cleavage: from bacteria to mammals. Arch Biochem Biophys 539(2):203–213. doi: 10.1016/ PubMedGoogle Scholar
  91. Takaichi S, Maoka T, Masamoto K (2001) Myxoxanthophyll in Synechocystis sp. PCC 6803 is myxol 2′-dimethyl-fucoside, (3R,2′S)-myxol 2′-(2,4-di-O-methyl-alpha-L-fucoside), not rhamnoside. Plant Cell Physiol 42(7):756–762PubMedGoogle Scholar
  92. Tao L, Schenzle A, Odom JM, Cheng Q (2005) Novel carotenoid oxidase involved in biosynthesis of 4,4′-diapolycopene dialdehyde. Appl Environ Microbiol 71(6):3294–3301. doi: 10.1128/AEM.71.6.3294-3301.2005 PubMedCentralPubMedGoogle Scholar
  93. Tao L, Yao H, Cheng Q (2007) Genes from a Dietzia sp. for synthesis of C40 and C50 beta-cyclic carotenoids. Gene 386(1–2):90–97. doi: 10.1016/j.gene.2006.08.006 PubMedGoogle Scholar
  94. Tatituri RV, Illarionov PA, Dover LG, Nigou J, Gilleron M, Hitchen P, Krumbach K, Morris HR, Spencer N, Dell A, Eggeling L, Besra GS (2007) Inactivation of Corynebacterium glutamicum NCgl0452 and the role of MgtA in the biosynthesis of a novel mannosylated glycolipid involved in lipomannan biosynthesis. J Biol Chem 282(7):4561–4572. doi: 10.1074/jbc.M608695200 PubMedGoogle Scholar
  95. Tjahjono AE, Kakizono T, Hayama Y, Nishio N, Nagai S (1994) Isolation of resistant mutants against carotenoid biosynthesis inhibitors for a green alga Haematococcus pluvialis, and their hybrid formation by protoplast fusion for breeding of higher astaxanthin producers. J Ferment Bioeng 77(4):352–357. doi: 10.1016/0922-338x(94)90003-5 Google Scholar
  96. To KY, Lai EM, Lee LY, Lin TP, Hung CH, Chen CL, Chang YS, Liu ST (1994) Analysis of the gene cluster encoding carotenoid biosynthesis in Erwinia herbicola Eho13. Microbiology 140(Pt 2):331–339PubMedGoogle Scholar
  97. Tobias AV, Arnold FH (2006) Biosynthesis of novel carotenoid families based on unnatural carbon backbones: a model for diversification of natural product pathways. Biochim Biophys Acta 1761(2):235–246. doi: 10.1016/j.bbalip.2006.01.003 PubMedGoogle Scholar
  98. Tsuchidate T, Tateno T, Okai N, Tanaka T, Ogino C, Kondo A (2011) Glutamate production from beta-glucan using endoglucanase-secreting Corynebacterium glutamicum. Appl Microbiol Biotechnol 90(3):895–901. doi: 10.1007/s00253-011-3116-7 PubMedGoogle Scholar
  99. Uhde A, Youn JW, Maeda T, Clermont L, Matano C, Kramer R, Wendisch VF, Seibold GM, Marin K (2013) Glucosamine as carbon source for amino acid-producing Corynebacterium glutamicum. Appl Microbiol Biotechnol 97(4):1679–1687. doi: 10.1007/s00253-012-4313-8 PubMedGoogle Scholar
  100. Ukibe K, Hashida K, Yoshida N, Takagi H (2009) Metabolic engineering of Saccharomyces cerevisiae for astaxanthin production and oxidative stress tolerance. Appl Environ Microbiol 75(22):7205–7211. doi: 10.1128/AEM.01249-09 PubMedCentralPubMedGoogle Scholar
  101. Umeno D, Tobias AV, Arnold FH (2005) Diversifying carotenoid biosynthetic pathways by directed evolution. Microbiol Mol Biol Rev 69(1):51–78. doi: 10.1128/MMBR.69.1.51-78.2005 PubMedCentralPubMedGoogle Scholar
  102. Vershinin A (1999) Biological functions of carotenoids—diversity and evolution. Biofactors 10(2–3):99–104PubMedGoogle Scholar
  103. Verwaal R, Wang J, Meijnen JP, Visser H, Sandmann G, van den Berg JA, van Ooyen AJ (2007) High-level production of beta-carotene in Saccharomyces cerevisiae by successive transformation with carotenogenic genes from Xanthophyllomyces dendrorhous. Appl Environ Microbiol 73(13):4342–4350. doi: 10.1128/AEM.02759-06 PubMedCentralPubMedGoogle Scholar
  104. Verwaal R, Jiang Y, Wang J, Daran JM, Sandmann G, van den Berg JA, van Ooyen AJ (2010) Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response. Yeast 27(12):983–998. doi: 10.1002/yea.1807 PubMedGoogle Scholar
  105. Wang F, Jiang JG, Chen Q (2007) Progress on molecular breeding and metabolic engineering of biosynthesis pathways of C30, C35, C40, C45, C50 carotenoids. Biotechnol Adv 25(3):211–222. doi: 10.1016/j.biotechadv.2006.12.001 PubMedGoogle Scholar
  106. Westfall PJ, Pitera DJ, Lenihan JR, Eng D, Woolard FX, Regentin R, Horning T, Tsuruta H, Melis DJ, Owens A, Fickes S, Diola D, Benjamin KR, Keasling JD, Leavell MD, McPhee DJ, Renninger NS, Newman JD, Paddon CJ (2012) Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proc Natl Acad Sci U S A 109(3):E111–E118. doi: 10.1073/pnas.1110740109 PubMedCentralPubMedGoogle Scholar
  107. Winterhalter P, Rouseff R (2001) Carotenoid-derived aroma compounds: an introduction carotenoid-derived aroma compounds. vol 802. ACS Symposium Series, Washington, DC, pp 1-17Google Scholar
  108. Xue J, Ahring BK (2011) Enhancing isoprene production by genetic modification of the 1-deoxy-d-xylulose-5-phosphate pathway in Bacillus subtilis. Appl Environ Microbiol 77(7):2399–2405. doi: 10.1128/AEM.02341-10 PubMedCentralPubMedGoogle Scholar
  109. Ye VM, Bhatia SK (2012) Pathway engineering strategies for production of beneficial carotenoids in microbial hosts. Biotechnol Lett 34(8):1405–1414. doi: 10.1007/s10529-012-0921-8 PubMedGoogle Scholar
  110. Yoshida K, Ueda S, Maeda I (2009) Carotenoid production in Bacillus subtilis achieved by metabolic engineering. Biotechnol Lett 31(11):1789–1793. doi: 10.1007/s10529-009-0082-6 PubMedGoogle Scholar
  111. Zeiger E, Zhu JX (1998) Role of zeaxanthin in blue light photoreception and the modulation of light-CO2 interactions in guard cells. J Exp Bot 49:433–442. doi: 10.1093/jexbot/49.suppl_1.433 Google Scholar
  112. Zhao J, Li Q, Sun T, Zhu X, Xu H, Tang J, Zhang X, Ma Y (2013) Engineering central metabolic modules of Escherichia coli for improving beta-carotene production. Metab Eng 17:42–50. doi: 10.1016/j.ymben.2013.02.002 PubMedGoogle Scholar
  113. Zhou K, Zou R, Zhang C, Stephanopoulos G, Too HP (2013) Optimization of amorphadiene synthesis in Bacillus subtilis via transcriptional, translational, and media modulation. Biotechnol Bioeng 110(9):2556–2561. doi: 10.1002/bit.24900 PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sabine A. E. Heider
    • 1
  • Petra Peters-Wendisch
    • 1
  • Volker F. Wendisch
    • 1
  • Jules Beekwilder
    • 2
  • Trygve Brautaset
    • 3
  1. 1.Chair of Genetics of Prokaryotes, Faculty of Biology & CeBiTecBielefeld UniversityBielefeldGermany
  2. 2.Plant Research InternationalWageningenThe Netherlands
  3. 3.Department of Molecular BiologySINTEF Materials and ChemistryTrondheimNorway

Personalised recommendations