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Microbial platforms to produce commercially vital carotenoids at industrial scale: an updated review of critical issues

  • Natural Products - Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Carotenoids are a diverse group of isoprenoid pigments that play crucial roles in plants, animals, and microorganisms, including body pigmentation, bio-communication, precursors for vitamin A, and potent antioxidant activities. With their potent antioxidant activities, carotenoids are emerging as molecules of vital importance in protecting against chronic degenerative disease, such as aging, cancer, cataract, cardiovascular, and neurodegenerative diseases. Due to countless functions in the cellular system, carotenoids are extensively used in dietary supplements, food colorants, aquaculture and poultry feed, nutraceuticals, and cosmetics. Moreover, the emerging demand for carotenoids in these vast areas has triggered their industrial-scale production. Currently, 80%–90% of carotenoids are produced synthetically by chemical synthesis. However, the demand for naturally produced carotenoids is increasing due to the health concern of synthetic counterparts. This article presents a review of the industrial production of carotenoids utilizing a number of diverse microbes, including microalgae, bacteria, and fungi, some of which have been genetically engineered to improve production titers.

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References

  1. Ambati RR, Phang S-M, Ravi S, Aswathanarayana RG (2014) Astaxanthin: sources, extraction, stability, biological activities and its commercial applications—a review. Mar Drugs 12:128–152. https://doi.org/10.3390/md12010128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Auerswald L, Gäde G (2008) Simultaneous extraction of chitin and astaxanthin from waste of lobsters Jasus lalandii, and use of astaxanthin as an aquacultural feed additive. Afr J Mar Sci 30:35–44. https://doi.org/10.2989/AJMS.2008.30.1.4.454

    Article  Google Scholar 

  3. Avalos J, Carmen Limón M (2015) Biological roles of fungal carotenoids. Curr Genet 61:309–324. https://doi.org/10.1007/s00294-014-0454-x

    Article  CAS  PubMed  Google Scholar 

  4. BBC Research (2018) The global market for carotenoids, FOD025F. Available via DIALOG. https://www.bccresearch.com/title of subordinate document, Accessed 25 Oct 2018

  5. Berman J, Zorrilla-López U, Farré G et al (2015) Nutritionally important carotenoids as consumer products. Phytochem Rev 14:727–743. https://doi.org/10.1007/s11101-014-9373-1

    Article  CAS  Google Scholar 

  6. Beuttler H, Hoffmann J, Jeske M et al (2011) Biosynthesis of zeaxanthin in recombinant Pseudomonas putida. Appl Microbiol Biotechnol 89:1137–1147. https://doi.org/10.1007/s00253-010-2961-0

    Article  CAS  PubMed  Google Scholar 

  7. Bhataya A, Schmidt-Dannert C, Lee PC (2009) Metabolic engineering of Pichia pastoris X-33 for lycopene production. Process Biochem 44:1095–1102. https://doi.org/10.1016/j.procbio.2009.05.012

    Article  CAS  Google Scholar 

  8. Borowitzka MA (2013) High-value products from microalgae—their development and commercialisation. J Appl Phycol 25:743–756. https://doi.org/10.1007/s10811-013-9983-9

    Article  CAS  Google Scholar 

  9. Bryon A, Kurlovs AH, Dermauw W et al (2017) Disruption of a horizontally transferred phytoene desaturase abolishes carotenoid accumulation and diapause in Tetranychus urticae. PNAS 114:E5871–E5880. https://doi.org/10.1073/pnas.1706865114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Campenni L, Nobre BP, Santos CA et al (2013) Carotenoid and lipid production by the autotrophic microalga Chlorella protothecoides under nutritional, salinity, and luminosity stress conditions. Appl Microbiol Biotechnol 97:1383–1393. https://doi.org/10.1007/s00253-012-4570-6

    Article  CAS  PubMed  Google Scholar 

  11. Cazzonelli CI, Pogson BJ (2010) Source to sink: regulation of carotenoid biosynthesis in plants. Trends Plant Sci 15:266–274

    Article  CAS  PubMed  Google Scholar 

  12. Choudhari SM, Ananthanarayan L, Singhal RS (2008) Use of metabolic stimulators and inhibitors for enhanced production of β-carotene and lycopene by Blakeslea trispora NRRL 2895 and 2896. Bioresour Technol 99:3166–3173. https://doi.org/10.1016/j.biortech.2007.05.051

    Article  CAS  PubMed  Google Scholar 

  13. de la Fuente JL, Rodríguez-Sáiz M, Schleissner C et al (2010) High-titer production of astaxanthin by the semi-industrial fermentation of Xanthophyllomyces dendrorhous. J Biotechnol 148:144–146. https://doi.org/10.1016/j.jbiotec.2010.05.004

    Article  CAS  PubMed  Google Scholar 

  14. Dufossé L (2017) Current carotenoid production using microorganisms. In: Singh OV (ed) Bio-pigmentation and biotechnological implementations. John Wiley and Sons, Inc., Hoboken, USA, pp 87–106

    Chapter  Google Scholar 

  15. Farré G, Sanahuja G, Naqvi S et al (2010) Travel advice on the road to carotenoids in plants. Plant Sci 179:28–48. https://doi.org/10.1016/j.plantsci.2010.03.009

    Article  CAS  Google Scholar 

  16. Fernández-Sevilla JM, Acién Fernández FG, Molina Grima E (2010) Biotechnological production of lutein and its applications. Appl Microbiol Biotechnol 86:27–40. https://doi.org/10.1007/s00253-009-2420-y

    Article  CAS  PubMed  Google Scholar 

  17. Frengova GI, Beshkova DM (2009) Carotenoids from Rhodotorula and Phaffia: yeasts of biotechnological importance. J Ind Microbiol Biotechnol 36:163–180. https://doi.org/10.1007/s10295-008-0492-9

    Article  CAS  PubMed  Google Scholar 

  18. García-Malea MC, Acién FG, Del Río E et al (2009) Production of astaxanthin by Haematococcus pluvialis: taking the one-step system outdoors. Biotechnol Bioeng 102:651–657. https://doi.org/10.1002/bit.22076

    Article  CAS  PubMed  Google Scholar 

  19. Giri AK, Rawat JK, Singh M et al (2015) Effect of lycopene against gastroesophageal reflux disease in experimental animals. BMC Complement Altern Med 15:110. https://doi.org/10.1186/s12906-015-0631-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gong M, Bassi A (2016) Carotenoids from microalgae: a review of recent developments. Biotechnol Adv 34:1396–1412. https://doi.org/10.1016/j.biotechadv.2016.10.005

    Article  CAS  PubMed  Google Scholar 

  21. Grama BS, Chader S, Khelifi D et al (2014) Induction of canthaxanthin production in a Dactylococcus microalga isolated from the Algerian Sahara. Bioresour Technol 151:297–305. https://doi.org/10.1016/j.biortech.2013.10.073

    Article  CAS  PubMed  Google Scholar 

  22. Hernández-Almanza A, Montañez J, Martínez G et al (2016) Lycopene: progress in microbial production. Trends Food Sci Technol 56:142–148. https://doi.org/10.1016/j.tifs.2016.08.013

    Article  CAS  Google Scholar 

  23. Jackson H, Braun CL, Ernst H (2008) The chemistry of novel xanthophyll carotenoids. Am J Cardiol 101:50D–57D. https://doi.org/10.1016/j.amjcard.2008.02.008

    Article  CAS  PubMed  Google Scholar 

  24. Kim J-S, Lee W-M, Rhee HC, Kim S (2016) Red paprika (Capsicum annuum L.) and its main carotenoids, capsanthin and β-carotene, prevent hydrogen peroxide-induced inhibition of gap-junction intercellular communication. Chem Biol Interact 254:146–155. https://doi.org/10.1016/j.cbi.2016.05.004

    Article  CAS  PubMed  Google Scholar 

  25. Kim JY, Paik JK, Kim OY et al (2011) Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men. Atherosclerosis 215:189–195. https://doi.org/10.1016/j.atherosclerosis.2010.11.036

    Article  CAS  PubMed  Google Scholar 

  26. Kim S-W, Kim J-B, Ryu J-M et al (2009) High-level production of lycopene in metabolically engineered E. coli. Process Biochem 44:899–905. https://doi.org/10.1016/j.procbio.2009.04.018

    Article  CAS  Google Scholar 

  27. Lemoine Y, Schoefs B (2010) Secondary ketocarotenoid astaxanthin biosynthesis in algae: a multifunctional response to stress. Photosynth Res 106:155–177. https://doi.org/10.1007/s11120-010-9583-3

    Article  CAS  PubMed  Google Scholar 

  28. Li J, Zhu D, Niu J et al (2011) An economic assessment of astaxanthin production by large scale cultivation of Haematococcus pluvialis. Biotechnol Adv 29:568–574. https://doi.org/10.1016/j.biotechadv.2011.04.001

    Article  CAS  PubMed  Google Scholar 

  29. Li X-R, Tian G-Q, Shen H-J, Liu J-Z (2015) Metabolic engineering of Escherichia coli to produce zeaxanthin. J Ind Microbiol Biotechnol 42:627–636. https://doi.org/10.1007/s10295-014-1565-6

    Article  CAS  PubMed  Google Scholar 

  30. Liang M-H, Zhu J, Jiang J-G (2017) Carotenoids biosynthesis and cleavage related genes from bacteria to plants. Crit Rev Food Sci Nutr 19:1–20. https://doi.org/10.1080/10408398.2017.1322552

    Article  CAS  Google Scholar 

  31. Lin J-H, Lee D-J, Chang J-S (2015) Lutein production from biomass: marigold flowers versus microalgae. Bioresour Technol 184:421–428. https://doi.org/10.1016/j.biortech.2014.09.099

    Article  CAS  PubMed  Google Scholar 

  32. Manayi A, Abdollahi M, Raman T et al (2016) Lutein and cataract: from bench to bedside. Crit Rev Biotechnol 36:829–839. https://doi.org/10.3109/07388551.2015.1049510

    Article  CAS  PubMed  Google Scholar 

  33. Mata-Gómez LC, Montañez JC, Méndez-Zavala A, Aguilar CN (2014) Biotechnological production of carotenoids by yeasts: an overview. Microb Cell Fact 13:12. https://doi.org/10.1186/1475-2859-13-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Moran NA, Jarvik T (2010) Lateral transfer of genes from fungi underlies carotenoid production in aphids. Science 328:624–627. https://doi.org/10.1126/science.1187113

    Article  CAS  PubMed  Google Scholar 

  35. Nasri Nasrabadi MR, Razavi SH (2010) Use of response surface methodology in a fed-batch process for optimization of tricarboxylic acid cycle intermediates to achieve high levels of canthaxanthin from Dietzia natronolimnaea HS-1. J Biosci Bioeng 109:361–368. https://doi.org/10.1016/j.jbiosc.2009.10.013

    Article  CAS  PubMed  Google Scholar 

  36. Nupur LNU, Vats A, Dhanda SK et al (2016) ProCarDB: a database of bacterial carotenoids. BMC Microbiol 16:96. https://doi.org/10.1186/s12866-016-0715-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Papp T, Csernetics A, Nagy G et al (2013) Canthaxanthin production with modified Mucor circinelloides strains. Appl Microbiol Biotechnol 97:4937–4950. https://doi.org/10.1007/s00253-012-4610-2

    Article  CAS  PubMed  Google Scholar 

  38. Park JS, Chyun JH, Kim YK et al (2010) Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans. Nutr Metab 7:18. https://doi.org/10.1186/1743-7075-7-18

    Article  CAS  Google Scholar 

  39. Prabhu S, Rekha PD, Young C-C et al (2013) Zeaxanthin production by novel marine isolates from coastal sand of India and its antioxidant properties. Appl Biochem Biotechnol 171:817–831. https://doi.org/10.1007/s12010-013-0397-6

    Article  CAS  PubMed  Google Scholar 

  40. Reyes LH, Gomez JM, Kao KC (2014) Improving carotenoids production in yeast via adaptive laboratory evolution. Metab Eng 21:26–33. https://doi.org/10.1016/j.ymben.2013.11.002

    Article  CAS  PubMed  Google Scholar 

  41. Riccioni G (2009) Carotenoids and cardiovascular disease. Curr Atheroscler Rep 11:434–439

    Article  CAS  PubMed  Google Scholar 

  42. Rodríguez-Sáiz M, de la Fuente JL, Barredo JL (2010) Xanthophyllomyces dendrorhous for the industrial production of astaxanthin. Appl Microbiol Biotechnol 88:645–658. https://doi.org/10.1007/s00253-010-2814-x

    Article  CAS  PubMed  Google Scholar 

  43. Ruiz-Sola MÁ, Rodríguez-Concepción M (2012) Carotenoid biosynthesis in Arabidopsis: a colorful pathway. Arabidopsis Book 10:e0158. https://doi.org/10.1199/tab.0158

    Article  PubMed  PubMed Central  Google Scholar 

  44. Saenge C, Cheirsilp B, Suksaroge TT, Bourtoom T (2011) Potential use of oleaginous red yeast Rhodotorula glutinis for the bioconversion of crude glycerol from biodiesel plant to lipids and carotenoids. Process Biochem 46:210–218. https://doi.org/10.1016/j.procbio.2010.08.009

    Article  CAS  Google Scholar 

  45. Saini RK, Keum Y-S (2017) Progress in microbial carotenoids production. Indian J Microbiol 57:129–130. https://doi.org/10.1007/s12088-016-0637-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Saini RK, Keum Y-S (2018) Significance of genetic, environmental, and pre- and postharvest factors affecting carotenoid contents in crops: a review. J Agric Food Chem 66:5310–5324. https://doi.org/10.1021/acs.jafc.8b01613

    Article  CAS  PubMed  Google Scholar 

  47. Saini RK, Moon SH, Gansukh E, Keum Y-S (2018) An efficient one-step scheme for the purification of major xanthophyll carotenoids from lettuce, and assessment of their comparative anticancer potential. Food Chem 266:56–65. https://doi.org/10.1016/j.foodchem.2018.05.104

    Article  CAS  PubMed  Google Scholar 

  48. Saini RK, Nile SH, Park SW (2015) Carotenoids from fruits and vegetables: chemistry, analysis, occurrence, bioavailability and biological activities. Food Res Int 76. Part 3:735–750. https://doi.org/10.1016/j.foodres.2015.07.047

    Article  CAS  Google Scholar 

  49. Sandmann G (2015) Carotenoids of biotechnological importance. In: Schrader J, Bohlmann J (eds) Biotechnology of isoprenoids. Springer International Publishing, Switzerland, pp 449–467

    Google Scholar 

  50. Schmidt I, Schewe H, Gassel S et al (2011) Biotechnological production of astaxanthin with Phaffia rhodozyma/Xanthophyllomyces dendrorhous. Appl Microbiol Biotechnol 89:555–571. https://doi.org/10.1007/s00253-010-2976-6

    Article  CAS  PubMed  Google Scholar 

  51. Solovchenko AE (2015) Recent breakthroughs in the biology of astaxanthin accumulation by microalgal cell. Photosynth Res 125:437–449. https://doi.org/10.1007/s11120-015-0156-3

    Article  CAS  PubMed  Google Scholar 

  52. Suganuma K, Nakajima H, Ohtsuki M, Imokawa G (2010) Astaxanthin attenuates the UVA-induced up-regulation of matrix-metalloproteinase-1 and skin fibroblast elastase in human dermal fibroblasts. J Dermatol Sci 58:136–142. https://doi.org/10.1016/j.jdermsci.2010.02.009

    Article  CAS  PubMed  Google Scholar 

  53. Sultan Alvi S, Ansari IA, Khan I et al (2017) Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia. Free Radic Biol Med 108:394–403. https://doi.org/10.1016/j.freeradbiomed.2017.04.012

    Article  CAS  PubMed  Google Scholar 

  54. Sun J, Shao Z, Zhao H et al (2012) Cloning and characterization of a panel of constitutive promoters for applications in pathway engineering in Saccharomyces cerevisiae. Biotechnol Bioeng 109:2082–2092. https://doi.org/10.1002/bit.24481

    Article  CAS  PubMed  Google Scholar 

  55. Sun T, Miao L, Li Q et al (2014) Production of lycopene by metabolically-engineered Escherichia coli. Biotechnol Lett 36:1515–1522. https://doi.org/10.1007/s10529-014-1543-0

    Article  CAS  PubMed  Google Scholar 

  56. Taniguchi H, Henke NA, Heider SAE, Wendisch VF (2017) Overexpression of the primary sigma factor gene sigA improved carotenoid production by Corynebacterium glutamicum: application to production of β-carotene and the non-native linear C50 carotenoid bisanhydrobacterioruberin. Metab Eng Comm 4:1–11. https://doi.org/10.1016/j.meteno.2017.01.001

    Article  Google Scholar 

  57. Thawornwiriyanun P, Tanasupawat S, Dechsakulwatana C et al (2012) Identification of newly zeaxanthin-producing bacteria isolated from sponges in the Gulf of Thailand and their zeaxanthin production. Appl Biochem Biotechnol 167:2357–2368. https://doi.org/10.1007/s12010-012-9760-2

    Article  CAS  PubMed  Google Scholar 

  58. Thies F, Mills LM, Moir S, Masson LF (2017) Cardiovascular benefits of lycopene: fantasy or reality? Proc Nutr Soc 76:122–129. https://doi.org/10.1017/S0029665116000744

    Article  CAS  PubMed  Google Scholar 

  59. Tian B, Hua Y (2010) Carotenoid biosynthesis in extremophilic deinococcus-thermus bacteria. Trends Microbiol 18:512–520. https://doi.org/10.1016/j.tim.2010.07.007

    Article  CAS  PubMed  Google Scholar 

  60. Virtamo J, Taylor PR, Kontto J et al (2014) Effects of α-tocopherol and β-carotene supplementation on cancer incidence and mortality: 18-year postintervention follow-up of the alpha-tocopherol, beta-carotene cancer prevention study. Int J Cancer 135:178–185. https://doi.org/10.1002/ijc.28641

    Article  CAS  PubMed  Google Scholar 

  61. Visioli F, Artaria C (2017) Astaxanthin in cardiovascular health and disease: mechanisms of action, therapeutic merits, and knowledge gaps. Food Funct 8:39–63. https://doi.org/10.1039/C6FO01721E

    Article  CAS  PubMed  Google Scholar 

  62. Viuda-Martos M, Sanchez-Zapata E, Sayas-Barberá E et al (2014) Tomato and tomato byproducts. Human health benefits of lycopene and its application to meat products: a review. Crit Rev Food Sci Nutr 54:1032–1049. https://doi.org/10.1080/10408398.2011.623799

    Article  CAS  PubMed  Google Scholar 

  63. Wang HH, Isaacs FJ, Carr PA et al (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature 460:894–898. https://doi.org/10.1038/nature08187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wichuk K, Brynjólfsson S, Fu W (2014) Biotechnological production of value-added carotenoids from microalgae: emerging technology and prospects. Bioengineered 5:204–208. https://doi.org/10.4161/bioe.28720

    Article  PubMed  PubMed Central  Google Scholar 

  65. Wobbe L, Remacle C (2015) Improving the sunlight-to-biomass conversion efficiency in microalgal biofactories. J Biotechnol 201:28–42. https://doi.org/10.1016/j.jbiotec.2014.08.021

    Article  CAS  PubMed  Google Scholar 

  66. Wu W, Li Y, Wu Y et al (2015) Lutein suppresses inflammatory responses through Nrf2 activation and NF-κB inactivation in lipopolysaccharide-stimulated BV-2 microglia. Mol Nutr Food Res 59:1663–1673. https://doi.org/10.1002/mnfr.201500109

    Article  CAS  PubMed  Google Scholar 

  67. Yan G, Wen K, Duan C (2012) Enhancement of β-carotene production by over-expression of HMG-CoA reductase coupled with addition of ergosterol biosynthesis inhibitors in recombinant Saccharomyces cerevisiae. Curr Microbiol 64:159–163. https://doi.org/10.1007/s00284-011-0044-9

    Article  CAS  PubMed  Google Scholar 

  68. Ye VM, Bhatia SK (2012) Pathway engineering strategies for production of beneficial carotenoids in microbial hosts. Biotechnol Lett 34:1405–1414. https://doi.org/10.1007/s10529-012-0921-8

    Article  CAS  PubMed  Google Scholar 

  69. Yeh T-J, Tseng Y-F, Chen Y-C et al (2017) Transcriptome and physiological analysis of a lutein-producing alga Desmodesmus sp. reveals the molecular mechanisms for high lutein productivity. Algal Res 21:103–119. https://doi.org/10.1016/j.algal.2016.11.013

    Article  Google Scholar 

  70. Yi X, Li J, Xu W et al (2015) Shrimp shell meal in diets for large yellow croaker Larimichthys croceus: effects on growth, body composition, skin coloration and anti-oxidative capacity. Aquaculture 441:45–50. https://doi.org/10.1016/j.aquaculture.2015.01.030

    Article  CAS  Google Scholar 

  71. Yoon S-H, Lee S-H, Das A et al (2009) Combinatorial expression of bacterial whole mevalonate pathway for the production of beta-carotene in E. coli. J Biotechnol 140:218–226. https://doi.org/10.1016/j.jbiotec.2009.01.008

    Article  CAS  PubMed  Google Scholar 

  72. Zhang C, Chen X, Lindley ND, Too H-P (2018) A “plug-n-play” modular metabolic system for the production of apocarotenoids. Biotechnol Bioeng 115:174–183. https://doi.org/10.1002/bit.26462

    Article  CAS  PubMed  Google Scholar 

  73. Zhao J, Li Q, Sun T et al (2013) Engineering central metabolic modules of Escherichia coli for improving β-carotene production. Metab Eng 17:42–50. https://doi.org/10.1016/j.ymben.2013.02.002

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This paper was supported by KU research professor program of Konkuk University, Seoul, Republic of Korea.

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  1. Department of Bioresources and Food Science, Konkuk University, Seoul, 143-701, Republic of Korea

    Ramesh Kumar Saini

  2. Institute of Natural Science and Agriculture, Konkuk University, Seoul, 143-701, Republic of Korea

    Ramesh Kumar Saini

  3. Department of Crop Science, Konkuk University, Seoul, 143-701, Republic of Korea

    Ramesh Kumar Saini & Young-Soo Keum

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Saini, R.K., Keum, YS. Microbial platforms to produce commercially vital carotenoids at industrial scale: an updated review of critical issues. J Ind Microbiol Biotechnol 46, 657–674 (2019). https://doi.org/10.1007/s10295-018-2104-7

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