Heterologous biosynthesis of artemisinic acid in Saccharomyces cerevisiae

Journal of Applied Microbiology

Volumn 120, Issue 6, 2016, Pages 1466-1478

  Li, C ^a,b,c   Li, J ^a,b   Wang, G ^a,b   Li, X ^a,b  

^a INSTITUTE OF GEOLOGY AND GEOPHYSICS   (China)

^b CHENGDU INSTITUTE OF BIOLOGY   (China)

^c UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

Author keywords

Artemisinic acid; Artemisinin; Bioinformatics; Heterologous biosynthesis; Omics; Saccharomyces cerevisiae

Indexed keywords

BIOCHEMISTRY; BIOINFORMATICS; YEAST;

'OMICS'; ANTIMALARIAL COMPOUNDS; ARTEMISINIC ACID; ARTEMISININ; CELL-BE; CELL/B.E; CELL/BE; HETEROLOGOUS BIOSYNTHESIS; PERFORMANCE; TARGET SITES;

BIOSYNTHESIS;

ARTEMISINIC ACID; ARTEMISININ; HYBRID PROTEIN; ANTIMALARIAL AGENT; ARTEMISININ DERIVATIVE;

BIOINFORMATICS; BIOLOGICAL PRODUCTION; BIOMANIPULATION; DRUG; DRUG DEVELOPMENT; GENE EXPRESSION; GENETIC ENGINEERING; GENOMICS; YEAST;

ARTEMISIA ANNUA; BIOINFORMATICS; BIOSYNTHESIS; CHLOROPLAST; COMPUTER MODEL; CYTOPLASM; DEFENSE MECHANISM; FEEDBACK SYSTEM; GENOTYPE; METABOLIC ENGINEERING; METABOLIC FLUX ANALYSIS; METABOLISM; NONHUMAN; REVIEW; SACCHAROMYCES CEREVISIAE; SYNTHESIS; UPREGULATION; BIOLOGY; MICROBIOLOGY;

SACCHAROMYCES CEREVISIAE;

ANTIMALARIALS; ARTEMISIA ANNUA; ARTEMISININS; BIOSYNTHETIC PATHWAYS; COMPUTATIONAL BIOLOGY; FEEDBACK, PHYSIOLOGICAL; INDUSTRIAL MICROBIOLOGY; SACCHAROMYCES CEREVISIAE;

EID: 84959449315     PISSN: 13645072     EISSN: 13652672     Source Type: Journal    
DOI: 10.1111/jam.13044     Document Type: Review

References (91)

1. Ajikumar, P.K., Tyo, K., Carlsen, S., Mucha, O., Phon, T.H. and Stephanopoulos, G. (2008) Terpenoids: opportunities for biosynthesis of natural product drugs using engineered microorganisms. Mol Pharm 5, 167-190.
2. Albertsen, L., Chen, Y., Bach, L.S., Rattleff, S., Maury, J., Brix, S., Nielsen, J. and Mortensen, U.H. (2011) Diversion of flux toward sesquiterpene production in Saccharomyces cerevisiae by fusion of host and heterologous enzymes. Appl Environ Microbiol 77, 1033-1040.
3. Alexey, V.A., Sabine, D., Philip, W. and Mewes, H.W. (2009) TICL-a web tool for network-based interpretation of compound lists inferred by high-throughput metabolomics. FEBS J 276, 2084-2094.
4. Baadhe, R.R., Mekala, N.K., Palagiri, S.R. and Parcha, S.R. (2012) Development of petri net-based dynamic model for improved production of farnesyl pyrophosphate by integrating mevalonate and methylerythritol phosphate pathways in yeast. Appl Biochem Biotechnol 167, 1172-1182.
5. Baadhe, R.R., Mekala, N.K., Parcha, S.R. and Prameela Devi, Y. (2013) Combination of ERG9 repression and enzyme fusion technology for improved production of amorphadiene in Saccharomyces cerevisiae. J Anal Methods Chem, doi: 10.1155/2013/140469.
6. Bailey, J.E., Sburlati, A., Hatzimanikatis, V., Lee, K., Renner, W.A. and Tsai, P.S. (2002) Inverse metabolic engineering: a strategy for directed genetic engineering of useful phenotypes. Biotechnol Bioeng 79, 568-579.
7. Barbacka, K. and Baer-Dubowska, W. (2011) Searching for artemisinin production improvement in plants and microorganisms. Curr Pharm Biotechnol 12, 1743-1751.
8. Basler, G. (2015) Computational prediction of essential metabolic genes using constraint-based approaches. Methods Mol Biol 1279, 183-204.
9. Bertea, C.M., Freije, J.R., van der Woude, H., Verstappen, F.W., Perk, L., Marquez, V., De Kraker, J.W., Posthumus, M.A. et al. (2005) Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua. Planta Med 71, 40-47.
10. Bouwmeester, H.J., Wallaart, T.E., Janssen, M.H., van Loo, B., Jansen, B.J., Posthumus, M.A., Schmidt, C.O., De Kraker, J.W. et al. (1999) Amorpha-4, 11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry 52, 843-854.
11. Brown, G.D. (2010) The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annuaL. (Qinghao). Molecules 15, 7603-7698.
12. Choi, Y.J. and Lee, S.Y. (2013) Microbial production of short-chain alkanes. Nature 502, 571-574.
13. Conrado, R.J., Varner, J.D. and DeLisa, M.P. (2008) Engineering the spatial organization of metabolic enzymes: mimicking nature's synergy. Curr Opin Biotechnol 19, 492-499.
14. Covello, P.S., Teoh, K.H., Polichuk, D.R., Reed, D.W. and Nowak, G. (2007) Functional genomics and the biosynthesis of artemisinin. Phytochemistry 68, 1864-1871.
15. Dahl, R.H., Zhang, F., Alonso-Gutierrez, J., Baidoo, E., Batth, T.S., Redding-Johanson, A.M., Petzold, C.J., Mukhopadhyay, A. et al. (2013) Engineering dynamic pathway regulation using stress-response promoters. Nat Biotechnol 31, 1039-1046.
16. Dai, Z., Liu, Y., Huang, L. and Zhang, X. (2012) Production of miltiradiene by metabolically engineered Saccharomyces cerevisiae. Biotechnol Bioeng 109, 2845-2853.
17. De, K.S.C., Thijs, I.M., Vanderleyden, J. and Marchal, K. (2006) Integration of omics data: how well does it work for bacteria? Mol Microbiol 62, 1239-1250.
18. Delabays, N., Simonnet, X. and Gaudin, M. (2001) The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars. Curr Med Chem 8, 1795-1801.
19. Diken, E., Ozer, T., Arikan, M., Emrence, Z., Oner, E.T., Ustek, D. and Arga, K.Y. (2015) Genomic analysis reveals the biotechnological and industrial potential of levan producing halophilic extremophile, Halomonas smyrnensis AAD6T. SpringerPlus 4, 393.
20. Donald, K.A., Hampton, R.Y. and Fritz, I.B. (1997) Effects of overproduction of the catalytic domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase on squalene synthesis in Saccharomyces cerevisiae. Appl Environ Microbiol 63, 3341-3344.
21. Farhi, M., Marhevka, E., Masci, T., Marcos, E., Eyal, Y., Ovadis, M., Abeliovich, H. and Vainstein, A. (2011) Harnessing yeast subcellular compartments for the production of plant terpenoids. Metab Eng 13, 474-481.
22. Han, J.L., Li, Z.Q. and Ye, H.C. (2008) Molecular cloning, prokaryotic expression, and enzyme activity assay of fps from Artemisiaannua strain 001. J Agric Univ Hebei 31, 71-75 (in Chinese with English abstract).
23. Hong, L. (2012) Genome-scale analysis and metabolic engineering strategies. Chin J Bioinform. 10, 55-60 (in Chinese with English abstract).
24. Huang, B., Guo, J., Sun, L. and Chen, W. (2013) ERG9 and COQ1 disruption reveals isoprenoids biosynthesis is closely related to mitochondrial function in Saccharomyces cerevisiae. Integr Biol (Camb) 5, 1282-1296.
25. Imam, S., Schauble, S., Brooks, A.N., Baliga, N.S. and Price, N.D. (2015) Data-driven integration of genome-scale regulatory and metabolic network models. Front Microbiol 6, 409.
26. Ji, Y., Xiao, J., Shen, Y., Ma, D., Li, Z., Pu, G., Li, X., Huang, L. et al. (2014) Cloning and characterization of AabHLH1, a bHLH transcription factor that positively regulates artemisinin biosynthesis in Artemisia annua. Plant Cell Physiol 55, 1592-1604.
27. Jorgensen, K., Rasmussen, A.V., Morant, M., Nielsen, A.H., Bjarnholt, N., Zagrobelny, M., Bak, S. and Moller, B.L. (2005) Metabolon formation and metabolic channeling in the biosynthesis of plant natural products. Curr Opin Plant Biol 8, 280-291.
28. Kampranis, S.C. and Makris, A.M. (2012) Developing a yeast cell factory for the production of terpenoids. Comput Struct Biotechnol J 3, e201210006.
29. Kavscek, M., Bhutada, G., Madl, T. and Natter, K. (2015) Optimization of lipid production with a genome-scale model of Yarrowia lipolytica. BMC Syst Biol 9, 72.
30. Kazuyuki, S. (2009) Toward systematic metabolic engineering based on the analysis of metabolic regulation by the integration of different levels of information. Bio-Chem Eng J 46, 235-251.
31. Keasling, J.D. (2012) Synthetic biology and the development of tools for metabolic engineering. Metab Eng 14, 189-195.
32. King, Z.A., Lloyd, C.J., Feist, A.M. and Palsson, B.O. (2015) Next-generation genome-scale models for metabolic engineering. Curr Opin Biotechnol 35, 23-29.
33. Kirby, J. and Keasling, J.D. (2009) Biosynthesis of plant isoprenoids: perspectives for microbial engineering. Annu Rev Plant Biol 60, 335-355.
34. Kong, J., Cheng, K. and Wang, L.N. (2007) Increase of copy number of HMG-CoA reductase and FPP synthase genes improves the amorpha4, 11-diene production in engineered yeast. Acta Pharm Sin 42, 1314-1319.
35. Kong, J., Wang, W., Wang, L. et al. (2009) The improvement of amorpha-4, 11-diene production by a yeast-conform variant. J Appl Microbiol 106, 941-951.
36. Kong, J., Yang, Y., Wang, W., Zheng, X.D., Cheng, K.D. and Zhu, P. (2013) Artemisinic acid: a promising molecule potentially suitable for the semi-synthesis of artemisinin. RSC Adv 3, 7622-7641.
37. Kourtz, L., Dillon, K., Daughtry, S., Madison, L.L., Peoples, O. and Snell, K.D. (2005) A novel thiolase-reductase gene fusion promotes the production of polyhydroxybutyrate in Arabidopsis. Plant Biotechnol J 3, 435-447.
38. Ku, B., Jeong, J.C. and Mijts, B.N. (2005) Preparation, characterization, and optimization of an in vitro C30 carotenoid pathway. Appl Environ Microbiol 71, 6578-6583.
39. Lenihan, J.R., Tsuruta, H., Diola, D., Renninger, N.S. and Regentin, R. (2008) Developing an industrial artemisinic acid fermentation process to support the cost-effective production of antimalarial artemisinin-based combination therapies. Biotechnol Prog 24, 1026-1032.
40. Li, X., He, H., Jianting, C., Hong, W. and Hechun, Y. (2012) An overview of heterologous organisms used to produce artemisinin and its precursors. Chin Bull Bot 47, 571-580 (in Chinese with English abstract).
41. Libourel, I.G. and Shachar-Hill, Y. (2008) Metabolic flux analysis in plants: from intelligent design to rational engineering. Annu Rev Plant Biol 59, 625-650.
42. Liu, C., Wang, Y., Ouyang, F., Ye, H.C. and Li, G.F. (1997) Production of artemisinin by hairy root cultures of Artemisia annua L. Biotechnol Lett 19, 927-930.
43. Liu, W., Huang, X. and Zhang, Q.Z. (2013) Advances in studies on biosynthesis and genetic engineering of artemisinin. Chin Tradit Herb Drugs 44, 101-107 (in Chinese with English abstract).
44. Lu, P. and Feng, M.G. (2008) Bifunctional enhancement of a beta-glucanase-xylanase fusion enzyme by optimization of peptide linkers. Appl Microbiol Biotechnol 79, 579-587.
45. Lu, S.J., Salleh, A.H., Mohamad, M.S., Deris, S., Omatu, S. and Yoshioka, M. (2014) Identification of gene knockout strategies using a hybrid of an ant colony optimization algorithm and flux balance analysis to optimize microbial strains. Comput Biol Chem 53, 175-183.
46. Misra, A., Conway, M.F., Johnnie, J., Qureshi, T.M., Lige, B., Derrick, A.M., Agbo, E.C. and Sriram, G. (2013) Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast. Front Microbiol 4, 200.
47. Nair, M.S., Acton, N., Klayman, D.L., Kendrick, K., Basile, D.V. and Mante, S. (1986) Production of artemisinin in tissue cultures of Artemisia annua. J Nat Prod 49, 504-507.
48. Nguyen, K.T., Arsenault, P.R. and Weathers, P.J. (2011) Trichomes + roots + ROS = artemisinin: regulating artemisinin bio-synthesis in Artemisia annua L. In Vitro Cell Dev Biol Plant 47, 329-338.
49. Nielsen, J. and Jewett, M.C. (2008) Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae. FEMS Yeast Res 08, 122-131.
50. Ohto, C., Muramatsu, M., Obata, S., Sakuradani, E. and Shimizu, S. (2010) Production of geranylgeraniol on overexpression of a prenyl diphosphate synthase fusion gene in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 87, 1327-1334.
51. Olsson, M.E., Olofsson, L.M. and Lindahl, A.L. (2009) Localization of enzymes of artemisinin biosynthesis to the apical cells of glandular secretory trichomes of Artemisia annua L. Phytochemistry 70, 1123-1128.
52. Paddon, C. (2013) In Isoprenoid Synthesis in Plants and Microorganisms. pp. 91-106, Springer.
53. Paddon, C.J. and Keasling, J.D. (2014) Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development. Nat Rev Microbiol 12, 355-367.
54. Paddon, C.J., Westfall, P.J., Pitera, D.J., Benjamin, K., Fisher, K., McPhee, D., Leavell, M.D., Tai, A. et al. (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496, 528-532.
55. Paniego, N.B. and Giulietti, A.M. (1996) Artemisinin production by Artemisia annua L-transformed organ cultures. Enzyme Microb Technol 18, 526-530.
56. Paradise, E.M., Kirby, J., Chan, R. and Keasling, J.D. (2008) Redirection of flux through the FPP branch-point in Saccharomyces cerevisiae by down-regulating squalene synthase. Biotechnol Bioeng 100, 371-378.
57. Parambil, L.K. and Sarkar, D. (2015) In silico analysis of bioethanol overproduction by genetically modified microorganisms in coculture fermentation. Biotechnol Res Int 00, 238082.
58. Patrick, M., Stefanie, W., Stefan, K., Bjorn, U., Nils, C., Jens, R., Julia, W., Luis, R.M. et al. (2008) Metabolomics- and proteomics-assisted genome annotation and analysis of the draft metabolic network of Chlamydomonas reinhardtii. Genetics 179, 157-166.
59. Peng, M.F., Chen, M. and Chen, R. (2011) The last gene involved in the MEP pathway of Artemisia annua: cloning and characterization and functional identification. J Med Plants Res 5, 223-230.
60. Picaud, S., Olofsson, L., Brodelius, M. and Brodelius, P.E. (2005) Expression, purification, and characterization of recombinant amorpha-4, 11-diene synthase from Artemisia annua L. Arch Biochem Biophys 436, 215-226.
61. Radhakrishnan, M., Anthony, P.B., Iman, F., Steve, V.D. and Christophe, H.S. (2005) Applications of metabolic modeling to drive bioprocess development for the production of value-added chemicals. Biotechnol Bioprocess Eng 10, 408-417.
62. Ram, M., Khan, M.A. and Jha, P. (2010) HMG-CoA reductase limits artemisinin biosynthesis and accumulation in Artemisia annua L. plants. Acta Physiol Plant 32, 859-866.
63. Ro, D.K., Paradise, E.M., Ouellet, M., Fisher, K.J., Newman, K.L., Ndungu, J.M., Ho, K.A. and Eachus, R.A. (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440, 940-943.
64. Sang, Y., Han, M., Dong-Yup, L., Hyung, S.C., Tae, Y.K. and Hongseok, Y. (2005) Systems-level analysis of genome-scale in silico metabolic models using MetaFluxNet. Biotechnol Bioprocess Eng 10, 425-431.
65. Sangwan, R.S., Agarwal, K. and Luthra, R. (1993) Biotransformation of arteannuic acid into arteannuin-B and artemisinin in Artemisia annua. Phytochemistry 34, 106-109.
66. Schenkman, J.B. and Jansson, I. (2003) The many roles of cytochrome b5. Pharmacol Ther 97, 139-152.
67. 2 study. Phytochemistry 71, 179-187.
68. Shiba, Y., Paradise, E.M., Kirby, J., Ro, D.K. and Keasling, J.D. (2007) Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae for high-level production of isoprenoids. Metab Eng 9, 160-168.
69. Souret, F.F., Weathers, P.J. and Wobbe, K.K. (2002) The mevalonate-independent pathway is expressed in transformed roots of Artemisia annua and regulated by light and culture age. In Vitro Cell Dev Biol 38, 581-588.
70. Sun, Z., Meng, H., Li, J., Wang, J., Li, Q., Wang, Y. and Zhang, Y. (2014) Identification of novel knockout targets for improving terpenoids biosynthesis in Saccharomyces cerevisiae. PLoS ONE 9, e112615.
71. Tae, Y.K., Seung, B.S., Hyun, U.K. and Lee, S.Y. (2008) Strategies for systems-level metabolic engineering. Biotech J 03, 612-623.
72. Teoh, K.H., Polichuk, D.R., Reed, D.W. and Covello, P.S. (2009) Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin biosynthesis in Artemisia annua. Botany 87, 635-642.
73. Tokuhiro, K., Muramatsu, M., Ohto, C., Kawaguchi, T., Obata, S., Muramoto, N., Hirai, M., Takahashi, H. et al. (2009) Overproduction of geranylgeraniol by metabolically engineered Saccharomyces cerevisiae. Appl Environ Microbiol 75, 5536-5543.
74. Vik, A. and Rine, J. (2001) Upc2p and Ecm22p, dual regulators of sterol biosynthesis in Saccharomyces cerevisiae. Mol Cell Biol 21, 6395-6405.
75. Wang, W., Yang, Y., Zheng, X.D., Huang, S.Q., Guo, L., Kong, J.Q. and Cheng, K.D. (2013) The advance in synthetic biology: towards a microbe-derived paclitaxel intermediates. Acta Pharm Sin 48, 187-192 (in Chinese with English abstract).
76. Weathers, P.J., Bunk, G. and McCoy, M.C. (2005) The effect of phytohormones on growth and artemisinin production in Artemisia annua hairy roots. Dev Bio-Plant 41, 47-53.
77. Westfall, P.J., Pitera, D.J., Lenihan, J.R., Eng, D., Woolard, F.X., Regentin, R., Horning, T., Tsuruta, H. et al. (2012) Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proc Natl Acad Sci USA 109, E111-E118.
78. White, N.J. (2008) Qinghaosu (artemisinin): the price of success. Science 320, 330-334.
79. Wu, L.J. (2009) Natural Pharmaceutical Chemistry, 5th edn. Beijing: People's Health Press.
80. Xie, W., Ye, L., Lv, X., Xu, H. and Yu, H. (2015) Sequential control of biosynthetic pathways for balanced utilization of metabolic intermediates in Saccharomyces cerevisiae. Metab Eng 28, 8-18.
81. Ye, V.M. and Bhatia, S.K. (2012) Metabolic engineering for the production of clinically important molecules: Omega-3 fatty acids, artemisinin, and taxol. Biotechnol J 7, 20-33.
82. Yuan, J. and Ching, C.B. (2015) Dynamic control of ERG9 expression for improved amorpha-4, 11-diene production in Saccharomyces cerevisiae. Microb Cell Fact 14, 38.
83. Zangar, R.C., Davydov, D.R. and Verma, S. (2004) Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol Appl Pharmacol 199, 316-331.
84. Zeng, Q.P. and Bao, F. (2011) Research achievements in the synthetic biology and metabolic engineering of artemisinin. Science Bulletin 56, 2289-2297 (in Chinese with English abstract).
85. Zeng, Q.P., Qiu, F. and Yuan, L. (2007) Production of artemisinin by genetically-modified microbes. Biotechnol Lett 30, 581-592.
86. Zhang, H., Im, S.C. and Waskell, L. (2007) Cytochrome b5 increases the rate of product formation by cytochrome P450 2B4 and competes with cytochrome P450 reductase for a binding site on cytochrome P450 2B4. J Biol Chem 282, 29766-29776.
87. Zhang, F., Carothers, J.M. and Keasling, J.D. (2012a) Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids. Nat Biotechnol 30, 354-359.
88. Zhang, Z.R., Liao, Z.H. and Peng, M.F. (2012b) Cloning and function analyses of HDS gene from Artemisia annua. Chin Tradit Herb Drugs 43, 148-154 (in Chinese with English abstract).
89. Zhang, F., Fu, X., Lv, Z., Lu, X., Shen, Q., Zhang, L., Zhu, M., Wang, G. et al. (2015) A basic leucine zipper transcription factor, AabZIP1, connects abscisic acid signaling with artemisinin biosynthesis in Artemisia annua. Mol Plant 8, 163-175.
90. Zhou, Y.J., Gao, W., Rong, Q., Jin, G., Chu, H., Liu, W., Yang, W., Zhu, Z. et al. (2012) Modular pathway engineering of diterpenoid synthases and the mevalonic acid pathway for miltiradiene production. J Am Chem Soc 134, 3234-3241.
91. Zomorrodi, A.R. and Maranas, C.D. (2010) Improving the iMM904 S. cerevisiae metabolic model using essentiality and synthetic lethality data. BMC Syst Biol 4, 178.