Increase of betulinic acid production in Saccharomyces cerevisiae by balancing fatty acids and betulinic acid forming pathways

Applied Microbiology and Biotechnology

Volumn 98, Issue 7, 2014, Pages 3081-3089

  Li, Jing ^a,b   Zhang, Yansheng ^a  

^a Wuhan Institute of Botany Chinese Academy of Sciences   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

Author keywords

Balancing carbon flux; Betulinic acid; Fatty acid; Saccharomyces cerevisiae

Indexed keywords

FATTY ACIDS; GENE EXPRESSION; SUBSTRATES;

ANTI-HIV ACTIVITY; BETULINIC ACID; BIOSYNTHETIC PATHWAY; CARBON FLUXES; FATTY ACID SYNTHESIS; FLUX DISTRIBUTIONS; METABOLIC ENGINEERING APPROACH; METABOLIC FLUX;

YEAST;

ACETYL COENZYME A; BETULIC ACID; FATTY ACID DERIVATIVE;

BIOENGINEERING; CARBON FLUX; FATTY ACID; GENE EXPRESSION; GROWTH; METABOLISM; TERPENE; YEAST;

ARTICLE; BIOSYNTHESIS; CONTROLLED STUDY; FATTY ACID SYNTHESIS; FUNGAL STRAIN; GENE EXPRESSION; METABOLIC ENGINEERING; NONHUMAN; PHENOTYPE; SACCHAROMYCES CEREVISIAE;

SACCHAROMYCES CEREVISIAE;

ANTI-HIV AGENTS; ANTINEOPLASTIC AGENTS; BIOSYNTHETIC PATHWAYS; FATTY ACIDS; GENE EXPRESSION; METABOLIC ENGINEERING; SACCHAROMYCES CEREVISIAE; TRITERPENES;

EID: 84898882028     PISSN: 01757598     EISSN: 14320614     Source Type: Journal    
DOI: 10.1007/s00253-013-5461-1     Document Type: Article

References (40)

1. Ajikumar PK, Xiao WH, Tyo KEJ, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli. Science 330:70-74
2. Bode HB, Zeggel B, Silakowski B, Wenzel SC, Reichenbach H, Müller R (2003) Steroid biosynthesis in prokaryotes: identification of myxobacterial steroids and cloning of the first bacterial 2,3(S)-oxidosqualene cyclase from the myxobacterium Stigmatella aurantiaca. Mol Microbiol 47:471-481
3. Boghigian BA, Armando J, Salas D, Pfeifer BA (2012) Computational identification of gene over-expression targets for metabolic engineering of taxadiene production. Appl Microbiol Biotechnol 93:2063-2073
4. Burke D DDS, Stearns T. (2000) Methods in yeast genetics: a Cold Spring Harbor Laboratory course manual. 2000 ed. Burke, D, New York
5. Donald KAG, Hampton RY, Fritz IB (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
6. Dzubak P, Hajduch M, Vydra D, Hustova A, Kvasnica M, Biedermann D, Markova L, Urban M, Sarek J (2006) Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat Prod Rep 23:394-411
7. Farmer WR, Liao JC (2000) Improving lycopene production in Escherichia coli by engineering metabolic control. Nat Biotechnol 18:533-537
8. Gietz RD, Woods RA (2002) Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 350:87-96
9. Hampton RY, Rine J (1994) Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. J Cell Biol 125:299-312
10. Hovland P, Flick J, Johnston M, Sclafani RA (1989) Galactose as a gratuitous inducer of GAL gene expression in yeasts growing on glucose. Gene 83:57-64
11. Huang LL, Li J, Ye HC, Li CF, Wang H, Liu BY, Zhang YS (2012) Molecular characterization of the pentacyclic triterpenoid biosynthetic pathway in Catharanthus roseus. Planta 236:1571-1581
12. Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A (2009) Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts. Molecules 14:2016-2031
13. Kaspera R, Croteau R (2006) Cytochrome P450 oxygenases of Taxol biosynthesis. Phytochem Rev 5:433-444
14. Kennedy MA, Bard M (2001) Positive and negative regulation of squalene synthase (ERG9), an ergosterol biosynthetic gene, in Saccharomyces cerevisiae. Biochim Biophys Acta-Gene Struct Expression 1517:177-189
15. Kim SW, Keasling JD (2001) Metabolic engineering of the nonmevalonate isopentenyl diphosphate synthesis pathway in Escherichia coli enhances lycopene production. Biotechnol Bioeng 72:408-415
16. Kim D, Chen ZD, Nguyen VT, Pezzuto JM, Qiu SX, Lu ZZ (1997) A concise semi-synthetic approach to betulinic acid from betulin. Synth Commun 27:1607-1612
17. Kirby J, Keasling JD (2008) Metabolic engineering of microorganisms for isoprenoid production. Nat Prod Rep 25:656-661
18. Kirby J, Romanini DW, Paradise EM, Keasling JD (2008) Engineering triterpene production in Saccharomyces cerevisiae-beta-amyrin synthase from Artemisia annua. Febs J 275:1852-1859
19. Kizer L, Pitera DJ, Pfleger BF, Keasling JD (2008) Application of functional genomics to pathway optimization for increased isoprenoid production. Appl Environ Microbiol 74:3229-3241
20. Leber R, Zenz R, Schrottner K, Fuchsbichler S, Puhringer B, Turnowsky F (2001) A novel sequence element is involved in the transcriptional regulation of expression of the ERG1 (squalene epoxidase) gene in Saccharomyces cerevisiae. Eur J Biochem 268:914-924
21. Liu J, Fu ML, Chen QH (2011) Biotransformation optimization of betulin into betulinic acid production catalysed by cultured Armillaria luteo-virens Sacc ZJUQH100-6 cells. J Appl Microbiol 110:90-97
22. Madsen KM, Udatha G, Semba S, Otero JM, Koetter P, Nielsen J, Ebizuka Y, Kushiro T, Panagiotou G (2011) Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers. PLoS One 6:e14763
23. Martin VJJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat Biotechnol 21:796-802
24. Matthews PD, Wurtzel ET (2000) Metabolic engineering of carotenoid accumulation in Escherichia coli by modulation of the isoprenoid precursor pool with expression of deoxyxylulose phosphate synthase. Appl Microbiol Biotechnol 53:396-400
25. Mumberg D, Muller R, Funk M (1995) Yeast vectors for the controlled expression of heterologous proteins in different genetic backgrounds. Gene 156:119-122
26. Nelson DR (1999) Cytochrome P450 and the individuality of species. Arch Biochem Biophys 369:1-10
27. Nijkamp JF, van den Broek M, Datema E, de Kok S, Bosman L, Luttik MA, Daran-Lapujade P, Vongsangnak W, Nielsen J, Heijne WHM, Klaassen P, Paddon CJ, Platt D, Kotter P, van Ham RC, Reinders MJT, Pronk JT, de Ridder D, Daran JM (2012) De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology. Microb Cell Fact 11:36
28. Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Jiang H, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496: 528-+
29. Pauwels K, Abadjieva A, Hilven P, Crabeel M (1999) A strong carbon source effect is mediated by pUC plasmid sequences in a series of classical yeast vectors designed for promoter characterization. Yeast 15:1269-1274
30. Pitera DJ, Paddon CJ, Newman JD, Keasling JD (2007) Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli. Metab Eng 9:193-207
31. Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MCY, Withers ST, Shiba Y, Sarpong R, Keasling JD (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940-943
32. Scholer A, Schuller HJ (1994) A carbon source-responsive promoter element necessary for activation of the isocitrate lyase gene ICL1 is common to genes of the gluconeogenic pathway in the yeast Saccharomyces cerevisiae. Mol Cell Biol 14:3613-3622
33. Schuler MA, Werck-Reichhart D (2003) Functional genomics of P450s. Annu Rev Plant Biol 54(1):629-667
34. Smith PF, Ogundele A, Forrest A, Wilton J, Salzwedel K, Doto J, Allaway GP, Martin DE (2007) Phase I and II study of the safety, virologic effect, and pharmacokinetics/pharmacodynamics of single-dose 3-O-(3′,3′- dimethylsuccinyl) betulinic acid (bevirimat) against human immunodeficiency virus infection. Antimicrob Agents Chemother 51:3574-3581
35. Urban P, Mignotte C, Kazmaier M, Delorme F, Pompon D (1997) Cloning, yeast expression, and characterization of the coupling of two distantly related Arabidopsis thaliana NADPH-Cytochrome P450 reductases with P450 CYP73A5. J Biol Chem 272:19176-19186
36. Veen M, Stahl U, Lang C (2003) Combined overexpression of genes of the ergosterol biosynthetic pathway leads to accumulation of sterols in Saccharomyces cerevisiae. FEMS Yeast Res 4:87-95
37. 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 109:111-118
38. Withers ST, Keasling JD (2007) Biosynthesis and engineering of isoprenoid small molecules. Appl Microbiol Biotechnol 73:980-990
39. Yogeeswari P, Sriram D (2005) Betulinic acid and its derivatives: A review on their biological properties. Curr Med Chem 12:657-666
40. Zuco V, Supino R, Righetti SC, Cleris L, Marchesi E, Gambacorti-Passerini C, Formelli F (2002) Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells. Cancer Lett 175:17-25