Skip to main content
SpringerLink
Log in

Isoflavonoid Production by Genetically Engineered Microorganisms

  • Reference work entry
  • First Online:
Natural Products

Abstract

Isoflavonoids are a class of plant natural products gaining attention due to their pharmaceutical properties. These natural compounds constitute a subclass of flavonoids, which belong to a broader class of plant products known as phenylpropanoids. Flavonoids have been associated with medicinal properties, while isoflavonoids have shown anticancer, antioxidant, and cardioprotective properties due to their role as inhibitors of estrogen receptors. Isoflavonoids are naturally produced by legumes and, more specifically, organisms belonging to the pea family. Harvesting of these natural products through traditional extraction processes is limited due to the low levels of these phytochemicals in plants, so alternative production platforms are required to reduce cost of production and increase availability. Over the last decade, researchers have engineered artificial flavonoid biosynthesis pathways into Escherichia coli and Saccharomyces cerevisiae to convert simple, renewable sugars like glucose into flavonoids at high production levels. This chapter outlines the metabolic engineering research that has enabled microbial production of plant flavonoids and further details the ongoing work aimed at producing both natural and non-natural isoflavonoids in microorganisms.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 2,999.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

3GT:

3-O-glucosyltransferase

4CL:

4-Coumarate-CoA ligase

ACC:

Acetyl-CoA carboxylase

Ala:

Alanine

ANR:

Anthocyanidin reductase

ANS:

Anthocyanidin synthase

API:

Active pharmaceutical ingredient

Arg:

Arginine

BDO:

Biphenyl dioxygenase

BMC:

Bacterial microcompartment

C4H:

Cinnamate 4-hydroxylase

CHI:

Chalcone isomerase

CHS:

Chalcone synthase

CPR:

Cytochrome P450 reductase

CUS:

Curcuminoid synthase

DFR:

Dihydroflavonol reductase

DH:

Salmonella typhimurium LT2 TDP-glucose 4,6-dehydratase

EPI:

Streptomyces antibioticus Tu99 TDP-4-keto-6-deoxyglucose 3,5-epimerase

ER:

Endoplasmic reticulum

F7GAT:

Flavonoid 7-O-glucuronosyltransferase

FHT:

Flavanone 3β-hydroxylase

FLS:

Flavonol synthase

FSI:

Soluble flavone synthase

FSII:

Membrane-bound flavone synthase

G1P:

Glucose-1-phosphate

G6P:

Glucose-6-phosphate

GALU:

Glucose-1-phosphate uridylyltransferase

GERF:

Streptomyces sp. KCTC 0041BP TDP-hexose 3-epimerase

GERK:

Streptomyces sp. KCTC 0041BP TDP-4-keto-6-deoxyglucose reductase

Glu:

Glutamic acid

Gly:

Glycine

HEK:

Human embryonic kidney cells

hER:

Human estrogen receptor

HI4′OMT:

2,7,4′-Trihydroxyisoflavanone 4′-O-methyltransferase

HID:

2-Hydroxyisoflavanone dehydratase

HIDH:

2-Hydroxyisoflavanone dehydratase hydroxy type

HIDM:

2-Hydroxyisoflavanone dehydratase methoxy type

IFR:

Isoflavone reductase

IFS:

Isoflavone synthase

Ile:

Isoleucine

k cat :

Turnover number

K m :

Michaelis constant

KR:

Streptomyces antibioticus Tu99 TDP-glucose 4-ketoreductase

LAR:

Leucoanthocyanidin reductase

LB:

Luria-Bertani medium

LDOX:

Leucoanthocyanidin dioxygenase

NADPH:

Nicotinamide adenine dinucleotide phosphate

NDK:

Nucleoside diphosphate kinase

NDO:

Naphthalene dioxygenase

PAL:

Phenylalanine ammonia-lyase

PGI:

Glucose-6-phosphate isomerase

PGM:

Phosphoglucomutase

Phe:

Phenylalanine

RCIFS:

Red clover isoflavone synthase

RCPR:

Rice cytochrome P450 reductase

SaOMT-2:

Streptomyces avermitilis MA-4680 7-O-methyltransferase

ScCCL:

Streptomyces coelicolor A3 cinnamate/coumarate:CoA ligase

Ser:

Serine

SERM:

Selective estrogen receptor modulator

STS:

Stilbene synthase

TAL:

Tyrosine ammonia-lyase

TB:

Terrific broth

TDP:

Thymidyldiphosphate

TGS:

Thermus caldophilus GK24 thymidyldiphosphoglucose synthase

Thr:

Threonine

Trp:

Tryptophan

Tyr:

Tyrosine

UDG:

Uridine diphosphoglucose dehydrogenase

UDP:

Uridine diphosphate

UGT:

Uridine diphosphate glycosyltransferase

UTP:

Uridine triphosphate

UXS1:

Uridine diphosphate glucuronic acid decarboxylase

Val:

Valine

V max :

Maximum reaction rate

References

  1. Demain AL, Fang A (2000) The natural functions of secondary metabolites. Adv Biochem Eng Biotechnol 69:1–39

    CAS  Google Scholar 

  2. Rhodes MJ (1994) Physiological roles for secondary metabolites in plants: some progress, many outstanding problems. Plant Mol Biol 24:1–20

    Article  CAS  Google Scholar 

  3. Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot 62:5–16

    Article  CAS  Google Scholar 

  4. Rodríguez-Concepción M, Boronat A (2002) Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids. A metabolic milestone achieved through genomics. Plant Physiol 130:1079–1089

    Article  CAS  Google Scholar 

  5. Demain AL (2000) Small bugs, big business: the economic power of the microbe. Biotechnol Adv 18:499–514

    Article  CAS  Google Scholar 

  6. Keasling JD (2010) Manufacturing molecules through metabolic engineering. Sci (NY) 330:1355–1358

    Article  CAS  Google Scholar 

  7. Dixon R, Steele C (1999) Flavonoids and isoflavonoids – a gold mine for metabolic engineering. Trends Plant Sci 4:394–400

    Article  Google Scholar 

  8. Dixon RA (2004) Phytoestrogens. Annu Rev Plant Biol 55:225–261

    Article  CAS  Google Scholar 

  9. Forkmann G, Martens S (2001) Metabolic engineering and applications of flavonoids. Curr Opin Biotechnol 12:155–160

    Article  CAS  Google Scholar 

  10. Yu O, McGonigle B (2005) Metabolic engineering of isoflavone biosynthesis. Adv Agron 86:147–190

    Article  CAS  Google Scholar 

  11. Yu O, Jez JM (2008) Nature’s assembly line: biosynthesis of simple phenylpropanoids and polyketides. Plant J Cell MolBiol 54:750–762

    Article  CAS  Google Scholar 

  12. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S (2003) Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst 95:906–913

    Article  CAS  Google Scholar 

  13. Siow RCM, Li FYL, Rowlands DJ, de Winter P, Mann GE (2007) Cardiovascular targets for estrogens and phytoestrogens: transcriptional regulation of nitric oxide synthase and antioxidant defense genes. Free Radic Biol Med 42:909–925

    Article  CAS  Google Scholar 

  14. Squadrito F, Altavilla D, Crisafulli A, Saitta A, Cucinotta D, Morabito N, D’Anna R, Corrado F, Ruggeri P, Frisina N, Squadrito G (2003) Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study. Am J Med 114:470–476

    Article  CAS  Google Scholar 

  15. Liu D, Zhen W, Yang Z, Carter JD, Si H, Reynolds KA (2006) Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes 55:1043–1050

    Article  CAS  Google Scholar 

  16. Rasbach KA, Schnellmann RG (2008) Isoflavones promote mitochondrial biogenesis. J Pharmacol Exp Ther 325:536–543

    Article  CAS  Google Scholar 

  17. Zhao L, Brinton RD (2007) WHI and WHIMS follow-up and human studies of soy isoflavones on cognition. Expert Rev Neurother 7:1549–1564

    Article  CAS  Google Scholar 

  18. Ji Z-N, Zhao WY, Liao GR, Choi RC, Lo CK, Dong TTX, Tsim KWK (2006) In vitro estrogenic activity of formononetin by two bioassay systems. Gynecol EndocrinolOff J Int Soc Gynecol Endocrinol 22:578–584

    Article  CAS  Google Scholar 

  19. McCarty MF (2006) Isoflavones made simple – genistein’s agonist activity for the beta-type estrogen receptor mediates their health benefits. Med hypotheses 66:1093–1114

    Article  CAS  Google Scholar 

  20. Zhao L, Brinton RD (2005) Structure-based virtual screening for plant-based ERbeta-selective ligands as potential preventative therapy against age-related neurodegenerative diseases. J Med Chem 48:3463–3466

    Article  CAS  Google Scholar 

  21. Lynd L, Wyman C, Gerngross T (1999) Biocommodity engineering. Biotechnol Prog 15:777–793

    Article  CAS  Google Scholar 

  22. Causey TB, Zhou S, Shanmugam KT, Ingram LO (2003) Engineering the metabolism of Escherichia coli W3110 for the conversion of sugar to redox-neutral and oxidized products: homoacetate production. Proc Natl Acad Sci USA 100:825–832

    Article  CAS  Google Scholar 

  23. Otero JM, Panagiotou G, Olsson L (2007) Fueling industrial biotechnology growth with bioethanol. Adv Biochem Eng Biotechnol 108:1–40

    CAS  Google Scholar 

  24. Lee JW, Kim TY, Jang Y-S, Choi S, Lee SY (2011) Systems metabolic engineering for chemicals and materials. Trends Biotechnol 29:370–378

    Article  CAS  Google Scholar 

  25. Jiang M, Stephanopoulos G, Pfeifer BA (2012) Toward biosynthetic design and implementation towards E. coli-derived Taxol and other heterologous polyisoprene compounds. Appl Environ Microbiol 78(8):2497–2504

    Article  CAS  Google Scholar 

  26. Huang B, Guo J, Yi B, Yu X, Sun L, Chen W (2008) Heterologous production of secondary metabolites as pharmaceuticals in Saccharomyces cerevisiae. Biotechnol Lett 30:1121–1137

    Article  CAS  Google Scholar 

  27. Chang MCY, Keasling JD (2006) Production of isoprenoid pharmaceuticals by engineered microbes. Nat Chem Biol 2:674–681

    Article  CAS  Google Scholar 

  28. Frense D (2007) Taxanes: perspectives for biotechnological production. Appl Microbiol Biotechnol 73:1233–1240

    Article  CAS  Google Scholar 

  29. Kuboyama T, Yokoshima S, Tokuyama H, Fukuyama T (2004) Stereocontrolled total synthesis of (+)-vincristine. Proc Natl Acad Sci USA 101:11966–11970

    Article  CAS  Google Scholar 

  30. Miyazaki T, Yokoshima S, Simizu S, Osada H, Tokuyama H, Fukuyama T (2007) Synthesis of (+)-vinblastine and its analogues. Org Lett 9:4737–4740

    Article  CAS  Google Scholar 

  31. Uchida K, Yokoshima S, Kan T, Fukuyama T (2006) Total synthesis of (+/−)-morphine. Org Lett 8:5311–5313

    Article  CAS  Google Scholar 

  32. Yokoshima S, Ueda T, Kobayashi S, Sato A, Kuboyama T, Tokuyama H, Fukuyama T (2002) Stereocontrolled total synthesis of (+)-vinblastine. J Am Chem Soc 124:2137–2139

    Article  CAS  Google Scholar 

  33. Lee DYW, Zhang W-Y, Karnati VVR (2003) Total synthesis of puerarin, an isoflavone C-glycoside. Tetrahedron Lett 44:6857–6859

    Article  CAS  Google Scholar 

  34. Heemstra JM, Kerrigan SA, Doerge DR, Helferich WG, Boulanger WA (2006) Total synthesis of (S)-equol. Org Lett 8:5441–5443

    Article  CAS  Google Scholar 

  35. Granados-Covarrubias EH, Maldonado LA (2009) A Wacker–Cook synthesis of isoflavones: formononetin. Tetrahedron Lett 50:1542–1545

    Article  CAS  Google Scholar 

  36. Stafford AM, Pazoles CJ, Siegel S, Yeh L-A (1998) Plant cell culture: a vehicle for drug delivery. In: Harvey AL (ed) Advances in drug discovery techniques. CRC Press, New York

    Google Scholar 

  37. Yukimune Y, Tabata H, Higashi Y, Hara Y (1996) Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures. Nat Biotechnol 14:1129–1132

    Article  CAS  Google Scholar 

  38. Witherup KM, Look SA, Stasko MW, Ghiorzi TJ, Muschik GM, Cragg GM (1990) Taxus spp. Needles contain amounts of taxol comparable to the bark of Taxus brevifolia: analysis and isolation. J Nat Prod 53:1249–1255

    Article  CAS  Google Scholar 

  39. Ajikumar PK, Xiao W-H, 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. Sci (NY) 330:70–74

    Article  CAS  Google Scholar 

  40. Filner P, Varner JE, Wray JL (1969) Environmental or developmental changes cause many enzyme activities of higher plants to rise or fall. Sci (NY) 165:358–367

    Article  CAS  Google Scholar 

  41. Shanks JV, Morgan J (1999) Plant “hairy root” culture. Curr Opin Biotechnol 10:151–155

    Article  CAS  Google Scholar 

  42. Zhang Y, Li S-Z, Li J, Pan X, Cahoon RE, Jaworski JG, Wang X, Jez JM, Chen F, Yu O (2006) Using unnatural protein fusions to engineer resveratrol biosynthesis in yeast and Mammalian cells. J Am Chem Soc 128:13030–13031

    Article  CAS  Google Scholar 

  43. Limem I, Guedon E, Hehn A, Bourgaud F, Chekir Ghedira L, Engasser J-M, Ghoul M (2008) Production of phenylpropanoid compounds by recombinant microorganisms expressing plant-specific biosynthesis genes. Process Biochem 43:463–479

    Article  CAS  Google Scholar 

  44. Fowler ZL, Koffas MA (2010) Microbial biosynthesis of fine chemicals: an emerging technology. In: Smolke CD (ed) The metabolic pathway engineering handbook. CRC Press, Boca Raton

    Google Scholar 

  45. Allister EM, Borradaile NM, Edwards JY, Huff MW (2005) Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein B100 secretion by the citrus flavonoid naringenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes. Diabetes 54:1676–1683

    Article  CAS  Google Scholar 

  46. Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, Aiello FB, Piantelli M (2000) Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J cancer 87:595–600, Journal international du cancer

    Article  CAS  Google Scholar 

  47. Hou D-X, Fujii M, Terahara N, Yoshimoto M (2004) Molecular mechanisms behind the chemopreventive effects of anthocyanidins. J Biomed Biotechnol 2004:321–325

    Article  Google Scholar 

  48. McDougall GJ, Stewart D (2005) The inhibitory effects of berry polyphenols on digestive enzymes. BioFactors (Oxf, Engl) 23:189–195

    Article  CAS  Google Scholar 

  49. Popiołkiewicz J, Polkowski K, Skierski JS, Mazurek AP (2005) In vitro toxicity evaluation in the development of new anticancer drugs-genistein glycosides. Cancer Lett 229:67–75

    Article  CAS  Google Scholar 

  50. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68:1375S–1379S

    CAS  Google Scholar 

  51. Pouget C, Lauthier F, Simon A, Fagnere C, Basly JP, Delage C, Chulia AJ (2001) Flavonoids: structural requirements for antiproliferative activity on breast cancer cells. Bioorg Med Chem Lett 11:3095–3097

    Article  CAS  Google Scholar 

  52. Hannum SM (2004) Potential impact of strawberries on human health: a review of the science. Crit Rev Food Sci Nutr 44:1–17

    Article  CAS  Google Scholar 

  53. Greenwald P (2004) Clinical trials in cancer prevention: current results and perspectives for the future. J Nutr 134:3507S–3512S

    CAS  Google Scholar 

  54. Nakajima J, Tanaka Y, Yamazaki M, Saito K (2001) Reaction mechanism from leucoanthocyanidin to anthocyanidin 3-glucoside, a key reaction for coloring in anthocyanin biosynthesis. J Biol Chem 276:25797–25803

    Article  CAS  Google Scholar 

  55. Winkel-Shirley B (2001) Flavonoid biosynthesis. A colorful model for genetics, biochemistry, cell biology, and biotechnology. Plant Physiol 126:485–493

    Article  CAS  Google Scholar 

  56. Du H, Huang Y, Tang Y (2010) Genetic and metabolic engineering of isoflavonoid biosynthesis. Appl Microbiol Biotechnol 86:1293–1312

    Article  CAS  Google Scholar 

  57. Leonard E, Yan Y, Fowler ZL, Li Z, Lim C-G, Lim K-H, Koffas MAG (2008) Strain improvement of recombinant Escherichia coli for efficient production of plant flavonoids. Mol Pharm 5:257–265

    Article  CAS  Google Scholar 

  58. Turnbull JJ, Nakajima J-I, Welford RWD, Yamazaki M, Saito K, Schofield CJ (2004) Mechanistic studies on three 2-oxoglutarate-dependent oxygenases of flavonoid biosynthesis: anthocyanidin synthase, flavonol synthase, and flavanone 3β-hydroxylase. J Biol Chem 279:1206–1216

    Article  CAS  Google Scholar 

  59. Gao X, Wang P, Tang Y (2010) Engineered polyketide biosynthesis and biocatalysis in Escherichia coli. Appl Microbiol Biotechnol 88:1233–1242

    Article  CAS  Google Scholar 

  60. Horinouchi S (2008) Combinatorial biosynthesis of non-bacterial and unnatural flavonoids, stilbenoids and curcuminoids by microorganisms. J Antibiot 61:709–728

    Article  CAS  Google Scholar 

  61. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC (2006) Multiple biological activities of curcumin: a short review. Life Sci 78:2081–2087

    Article  CAS  Google Scholar 

  62. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB (2007) Bioavailability of curcumin: problems and promises. Mol Pharm 4:807–818

    Article  CAS  Google Scholar 

  63. Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007) Curcumin: the Indian solid gold. Adv Exp Med Biol 595:1–75

    Article  Google Scholar 

  64. Boghigian BA, Pfeifer BA (2008) Current status, strategies, and potential for the metabolic engineering of heterologous polyketides in Escherichia coli. Biotechnol Lett 30:1323–1330

    Article  CAS  Google Scholar 

  65. Leonard E, Yan Y, Lim KH, Koffas MAG (2005) Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis in Saccharomyces cerevisiae. Appl Environ Microbiol 71:8241–8248

    Article  CAS  Google Scholar 

  66. Kyle JAM, Duthie GG (2005) Flavonoids in foods. In: Andersen Ø, Markham K (eds) Flavonoids: chemistry, biochemistry and applications. CRC Press, Boca Raton, pp 219–262

    Chapter  Google Scholar 

  67. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747

    CAS  Google Scholar 

  68. Hollman PC, Arts IC (2000) Flavonols, flavones and flavanols – nature, occurrence and dietary burden. J Sci Food Agric 80:1081–1093

    Article  CAS  Google Scholar 

  69. Akashi T, Aoki T, Ayabe SI (1999) Cloning and functional expression of a cytochrome P450 cDNA encoding 2-hydroxyisoflavanone synthase involved in biosynthesis of the isoflavonoid skeleton in licorice. Plant Physiol 121:821–828

    Article  CAS  Google Scholar 

  70. Steele CL, Gijzen M, Qutob D, Dixon RA (1999) Molecular characterization of the enzyme catalyzing the aryl migration reaction of isoflavonoid biosynthesis in soybean. Arch Biochem Biophys 367:146–150

    Article  CAS  Google Scholar 

  71. Akashi T, Aoki T, Ayabe S-I (2005) Molecular and biochemical characterization of 2-hydroxyisoflavanone dehydratase. Involvement of carboxylesterase-like proteins in leguminous isoflavone biosynthesis. Plant Physiol 137:882–891

    Article  CAS  Google Scholar 

  72. Grotewold E (ed) (2006) The science of flavonoids. Springer, New York

    Google Scholar 

  73. Fukutake M, Takahashi M, Ishida K, Kawamura H, Sugimura T, Wakabayashi K (1996) Quantification of genistein and genistin in soybeans and soybean products. Food Chem Toxicol 34:457–461

    Article  CAS  Google Scholar 

  74. Espín JC, García-Conesa MT, Tomás-Barberán FA (2007) Nutraceuticals: facts and fiction. Phytochemistry 68:2986–3008

    Article  CAS  Google Scholar 

  75. Crozier A, Clifford MN, Ashihara H (eds) (2008) Plant secondary metabolites: occurrence, structure and role in the human diet. Blackwell Publishing Ltd, Oxford

    Google Scholar 

  76. Martens S, Preuß A, Matern U (2010) Multifunctional flavonoid dioxygenases: flavonol and anthocyanin biosynthesis in Arabidopsis thaliana L. Phytochemistry 71:1040–1049

    Article  CAS  Google Scholar 

  77. Davies KM, Schwinn KE (2005) Molecular biology and biotechnology of flavonoid biosynthesis. In: Andersen ØM, Markham KR (eds) Flavonoids: chemistry, biochemistry and applications. CRC Press, Boca Raton, pp 143–218

    Chapter  Google Scholar 

  78. Kaneko M, Hwang EI, Ohnishi Y, Horinouchi S (2003) Heterologous production of flavanones in Escherichia coli: potential for combinatorial biosynthesis of flavonoids in bacteria. J Ind Microbiol Biotechnol 30:456–461

    Article  CAS  Google Scholar 

  79. Hwang EI, Kaneko M, Ohnishi Y, Horinouchi S (2003) Production of plant-specific flavanones by Escherichia coli containing an artificial gene cluster. Appl Environ Microbiol 69:2699–2706

    Article  CAS  Google Scholar 

  80. Miyahisa I, Kaneko M, Funa N, Kawasaki H, Kojima H, Ohnishi Y, Horinouchi S (2005) Efficient production of (2S)-flavanones by Escherichia coli containing an artificial biosynthetic gene cluster. Appl Microbiol Biotechnol 68:498–504

    Article  CAS  Google Scholar 

  81. Kyndt JA, Meyer TE, Cusanovich MA, Van Beeumen JJ (2002) Characterization of a bacterial tyrosine ammonia lyase, a biosynthetic enzyme for the photoactive yellow protein. FEBS Lett 512:240–244

    Article  CAS  Google Scholar 

  82. Chemler JA, Yan Y, Leonard E, Koffas MAG (2007) Combinatorial mutasynthesis of flavonoid analogues from acrylic acids in microorganisms. Org Lett 9:1855–1858

    Article  CAS  Google Scholar 

  83. Chemler JA (2009) Metabolic engineering of Escherichia coli and Saccharomyces cerevisiae to mutasynthesize natural phenylpropanoids and novel analogs

    Google Scholar 

  84. Miyahisa I, Funa N, Ohnishi Y, Martens S, Moriguchi T, Horinouchi S (2006) Combinatorial biosynthesis of flavones and flavonols in Escherichia coli. Appl Microbiol Biotechnol 71:53–58

    Article  CAS  Google Scholar 

  85. Yan Y, Chemler J, Huang L, Martens S, Koffas MAG (2005) Metabolic engineering of anthocyanin biosynthesis in Escherichia coli. Appl Environ Microbiol 71:3617–3623

    Article  CAS  Google Scholar 

  86. Leonard E, Chemler J, Lim KH, Koffas MAG (2006) Expression of a soluble flavone synthase allows the biosynthesis of phytoestrogen derivatives in Escherichia coli. Appl Microbiol Biotechnol 70:85–91

    Article  CAS  Google Scholar 

  87. Leonard E, Yan Y, Koffas MAG (2006) Functional expression of a P450 flavonoid hydroxylase for the biosynthesis of plant-specific hydroxylated flavonols in Escherichia coli. Metab Eng 8:172–181

    Article  CAS  Google Scholar 

  88. Yan Y, Huang L, Koffas MAG (2007) Biosynthesis of 5-deoxyflavanones in microorganisms. Biotechnol J 2:1250–1262

    Article  CAS  Google Scholar 

  89. Leonard E, Lim K-H, Saw P-N, Koffas MAG (2007) Engineering central metabolic pathways for high-level flavonoid production in Escherichia coli. Appl Environ Microbiol 73:3877–3886

    Article  CAS  Google Scholar 

  90. Chemler JA, Lock LT, Koffas MAG, Tzanakakis ES (2007) Standardized biosynthesis of flavan-3-ols with effects on pancreatic beta-cell insulin secretion. Appl Microbiol Biotechnol 77:797–807

    Article  CAS  Google Scholar 

  91. Jiang H, Wood KV, Morgan JA (2005) Metabolic engineering of the phenylpropanoid pathway in Saccharomyces cerevisiae. Appl Environ Microbiol 71:2962

    Article  CAS  Google Scholar 

  92. Yan Y, Kohli A, Koffas MAG (2005) Biosynthesis of natural flavanones in Saccharomyces cerevisiae. Appl Environ Microbiol 71:5610–5613

    Article  CAS  Google Scholar 

  93. Lim CG, Fowler ZL, Hueller T, Schaffer S, Koffas MAG (2011) High-yield resveratrol production in engineered Escherichia coli. Appl Environ Microbiol 77:3451–3460

    Article  CAS  Google Scholar 

  94. Beekwilder J, Wolswinkel R, Jonker H, Hall R, de Vos CHR, Bovy A (2006) Production of resveratrol in recombinant microorganisms. Appl Environ Microbiol 72:5670–5672

    Article  CAS  Google Scholar 

  95. Watts KT, Lee PC, Schmidt-Dannert C (2006) Biosynthesis of plant-specific stilbene polyketides in metabolically engineered Escherichia coli. BMC Biotechnol 6:22

    Article  CAS  Google Scholar 

  96. Yan Y, Li Z, Koffas MAG (2008) High-yield anthocyanin biosynthesis in engineered Escherichia coli. Biotechnol Bioeng 100:126–140

    Article  CAS  Google Scholar 

  97. Watts KT, Lee PC, Schmidt-Dannert C (2004) Exploring recombinant flavonoid biosynthesis in metabolically engineered Escherichia coli. Chembiochem: Eur J Chem Biol 5:500–507

    Article  CAS  Google Scholar 

  98. He X-Z, Li W-S, Blount JW, Dixon RA (2008) Regioselective synthesis of plant (iso)flavone glycosides in Escherichia coli. Appl Microbiol Biotechnol 80:253–260

    Article  CAS  Google Scholar 

  99. Katsuyama Y, Hirose Y, Funa N, Ohnishi Y, Horinouchi S (2010) Precursor-directed biosynthesis of curcumin analogs in Escherichia coli. Biosci Biotechnol Biochem 74:641–645

    Article  CAS  Google Scholar 

  100. Katsuyama Y, Funa N, Miyahisa I, Horinouchi S (2007) Synthesis of unnatural flavonoids and stilbenes by exploiting the plant biosynthetic pathway in Escherichia coli. Chem Biol 14:613–621

    Article  CAS  Google Scholar 

  101. Trantas E, Panopoulos N, Ververidis F (2009) Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae. Metab Eng 11:355–366

    Article  CAS  Google Scholar 

  102. Jiang H, Morgan JA (2004) Optimization of an in vivo plant P450 monooxygenase system in Saccharomyces cerevisiae. Biotechnol Bioeng 85:130–137

    Article  CAS  Google Scholar 

  103. Kim DH, Kim BG, Lee HJ, Lim Y, Hur HG, Ahn J-H (2005) Enhancement of isoflavone synthase activity by co-expression of P450 reductase from rice. Biotechnol Lett 27:1291–1294

    Article  CAS  Google Scholar 

  104. Ralston L, Subramanian S, Matsuno M, Yu O (2005) Partial reconstruction of flavonoid and isoflavonoid biosynthesis in yeast using soybean type I and type II chalcone isomerases. Plant Physiol 137:1375–1388

    Article  CAS  Google Scholar 

  105. Becker JVW, Armstrong GO, van der Merwe MJ, Lambrechts MG, Vivier MA, Pretorius IS (2003) Metabolic engineering of Saccharomyces cerevisiae for the synthesis of the wine-related antioxidant resveratrol. FEMS Yeast Res 4:79–85

    Article  CAS  Google Scholar 

  106. Ro D-K, Douglas CJ (2004) Reconstitution of the entry point of plant phenylpropanoid metabolism in yeast (Saccharomyces cerevisiae): implications for control of metabolic flux into the phenylpropanoid pathway. J Biol Chem 279:2600–2607

    Article  CAS  Google Scholar 

  107. Vannelli T, Wei Qi W, Sweigard J, Gatenby AA, Sariaslani FS (2007) Production of p-hydroxycinnamic acid from glucose in Saccharomyces cerevisiae and Escherichia coli by expression of heterologous genes from plants and fungi. Metab Eng 9:142–151

    Article  CAS  Google Scholar 

  108. Barnes HJ, Arlotto MP, Waterman MR (1991) Expression and enzymatic activity of recombinant cytochrome P450 17 alpha-hydroxylase in Escherichia coli. Proc Natl Acad Sci USA 88:5597–5601

    Article  CAS  Google Scholar 

  109. Williams PA, Cosme J, Sridhar V, Johnson EF, McRee DE (2000) Microsomal cytochrome P450 2C5: comparison to microbial P450s and unique features. J Inorg Biochem 81:183–190

    Article  CAS  Google Scholar 

  110. Katsuyama Y, Miyahisa I, Funa N, Horinouchi S (2007) One-pot synthesis of genistein from tyrosine by coincubation of genetically engineered Escherichia coli and Saccharomyces cerevisiae cells. Appl Microbiol Biotechnol 73:1143–1149

    Article  CAS  Google Scholar 

  111. Horinouchi S (2009) Combinatorial biosynthesis of plant medicinal polyketides by microorganisms. Curr Opin Chem Biol 13:197–204

    Article  CAS  Google Scholar 

  112. Tian L, Dixon RA (2006) Engineering isoflavone metabolism with an artificial bifunctional enzyme. Planta 224:496–507

    Article  CAS  Google Scholar 

  113. Porter TD, Wilson TE, Kasper CB (1987) Expression of a functional 78,000 dalton mammalian flavoprotein, NADPH-cytochrome P-450 oxidoreductase, in Escherichia coli. Arch Biochem Biophys 254:353–367

    Article  CAS  Google Scholar 

  114. Leonard E, Koffas MAG (2007) Engineering of artificial plant cytochrome P450 enzymes for synthesis of isoflavones by Escherichia coli. Appl Environ Microbiol 73:7246–7251

    Article  CAS  Google Scholar 

  115. Kim DH, Kim B-G, Jung NR, Ahn J-H (2009) Production of genistein from naringenin using Escherichia coli containing isoflavone synthase-cytochrome P450 reductase fusion protein. J Microbiol Biotechnol 19:1612–1616

    CAS  Google Scholar 

  116. Ro D-K, Ehlting J, Douglas CJ (2002) Cloning, functional expression, and subcellular localization of multiple NADPH-cytochrome P450 reductases from hybrid poplar. Plant Physiol 130:1837–1851

    Article  CAS  Google Scholar 

  117. Chemler JA, Lim CG, Daiss JL, Koffas MAG (2010) A versatile microbial system for biosynthesis of novel polyphenols with altered estrogen receptor binding activity. Chem Biol 17:392–401

    Article  CAS  Google Scholar 

  118. Lim E-K, Ashford DA, Hou B, Jackson RG, Bowles DJ (2004) Arabidopsis glycosyltransferases as biocatalysts in fermentation for regioselective synthesis of diverse quercetin glucosides. Biotechnol Bioeng 87:623–631

    Article  CAS  Google Scholar 

  119. Willits MG, Giovanni M, Prata RT, Kramer CM, De Luca V, Steffens JC, Graser G (2004) Bio-fermentation of modified flavonoids: an example of in vivo diversification of secondary metabolites. Phytochemistry 65:31–41

    Article  CAS  Google Scholar 

  120. Deavours BE, Dixon RA, Division PB, Roberts S, Foundation N (2005) Metabolic engineering of isoflavonoid biosynthesis in alfalfa. Plant Physiol 138:2245–2259

    Article  CAS  Google Scholar 

  121. Liu C-J, Blount JW, Steele CL, Dixon RA (2002) Bottlenecks for metabolic engineering of isoflavone glycoconjugates in Arabidopsis. Proc Natl Acad Sci USA 99:14578–14583

    Article  CAS  Google Scholar 

  122. Yu O, Jung W, Shi J, Croes RA, Fader GM, McGonigle B, Odell JT (2000) Production of the isoflavones genistein and daidzein in non-legume dicot and monocot tissues. Plant Physiol 124:781–794

    Article  CAS  Google Scholar 

  123. Yu O, Shi J, Hession AO, Maxwell CA, McGonigle B, Odell JT (2003) Metabolic engineering to increase isoflavone biosynthesis in soybean seed. Phytochemistry 63:753–763

    Article  CAS  Google Scholar 

  124. Hollman PC, Katan MB (1999) Health effects and bioavailability of dietary flavonols. Free Radic Res 31(Suppl):S75–S80

    Article  CAS  Google Scholar 

  125. Hollman PC, Katan MB (1998) Bioavailability and health effects of dietary flavonols in man. Archives of toxicology. Supplement. = Archiv für Toxikologie. Supplement. 20:237–248

    Google Scholar 

  126. Hollman PC, Bijsman MN, van Gameren Y, Cnossen EP, de Vries JH, Katan MB (1999) The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 31:569–573

    Article  CAS  Google Scholar 

  127. Smith GJ, Thomsen SJ, Markham KR, Andary C, Cardon D (2000) The photostabilities of naturally occurring 5-hydroxyflavones, flavonols, their glycosides and their aluminium complexes. J Photochem Photobiol: Chem 136:87–91

    Article  CAS  Google Scholar 

  128. Crespy V, Morand C, Besson C, Manach C, Démigné C, Rémésy C (2001) Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats. J Nutr 131:2109–2114

    CAS  Google Scholar 

  129. Graefe EU, Wittig J, Mueller S, Riethling AK, Uehleke B, Drewelow B, Pforte H, Jacobasch G, Derendorf H, Veit M (2001) Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol 41:492–499

    Article  CAS  Google Scholar 

  130. Bouktaib M, Atmani A, Rolando C (2002) Regio- and stereoselective synthesis of the major metabolite of quercetin, quercetin-3-O-β-d-glucuronide. Tetrahedron Lett 43:6263–6266

    Article  CAS  Google Scholar 

  131. Harborne JB, Baxter H, Harborne JB (1999) The handbook of natural flavonoids. Wiley, Chichester

    Google Scholar 

  132. Lim SS, Jung SH, Ji J, Shin KH, Keum SR (2001) Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. J Pharm Pharmacol 53:653–668

    Article  CAS  Google Scholar 

  133. Mavel S, Dikic B, Palakas S, Emond P, Greguric I, de Gracia AG, Mattner F, Garrigos M, Guilloteau D, Katsifis A (2006) Synthesis and biological evaluation of a series of flavone derivatives as potential radioligands for imaging the multidrug resistance-associated protein 1 (ABCC1/MRP1). Bioorg Med Chem 14:1599–1607

    Article  CAS  Google Scholar 

  134. Mao Z, Shin H-D, Chen RR (2006) Engineering the E. coli UDP-glucose synthesis pathway for oligosaccharide synthesis. Biotechnol Prog 22:369–374

    Article  CAS  Google Scholar 

  135. Li Z (2008) High yield anthocyanin biosynthesis in metabolic engineering Escherichia coli. Master of Science, Department of Chemical and Biological Engineering

    Google Scholar 

  136. Yan Y (2008) Constructing microbial production platform for the biosynthesis of natural drug candidates-flavonoids

    Google Scholar 

  137. Jung W, Yu O, Lau SM, O’Keefe DP, Odell J, Fader G, McGonigle B (2000) Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes. Nat Biotechnol 18:208–212

    Article  CAS  Google Scholar 

  138. Noguchi A, Horikawa M, Fukui Y, Fukuchi-Mizutani M, Iuchi-Okada A, Ishiguro M, Kiso Y, Nakayama T, Ono E (2009) Local differentiation of sugar donor specificity of flavonoid glycosyltransferase in Lamiales. Plant Cell 21:1556–1572

    Article  CAS  Google Scholar 

  139. Osmani SA, Bak S, Imberty A, Olsen CE, Møller BL (2008) Catalytic key amino acids and UDP-sugar donor specificity of a plant glucuronosyltransferase, UGT94B1: molecular modeling substantiated by site-specific mutagenesis and biochemical analyses. Plant Physiol 148:1295–1308

    Article  CAS  Google Scholar 

  140. He X-Z, Wang X, Dixon RA (2006) Mutational analysis of the Medicago glycosyltransferase UGT71G1 reveals residues that control regioselectivity for (iso)flavonoid glycosylation. J Biol Chem 281:34441–34447

    Article  CAS  Google Scholar 

  141. Modolo LV, Escamilla-Treviño LL, Dixon RA, Wang X (2009) Single amino acid mutations of Medicago glycosyltransferase UGT85H2 enhance activity and impart reversibility. FEBS Lett 583:2131–2135

    Article  CAS  Google Scholar 

  142. Funa N, Ohnishi Y, Ebizuka Y, Horinouchi S (2002) Alteration of reaction and substrate specificity of a bacterial type III polyketide synthase by site-directed mutagenesis. Biochem J 367:781–789

    Article  CAS  Google Scholar 

  143. Morita H, Yamashita M, Shi S-P, Wakimoto T, Kondo S, Kato R, Sugio S, Kohno T, Abe I (2011) Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase. Proc Natl Acad Sci USA 108:13504–13509

    Article  CAS  Google Scholar 

  144. Wang Y, Halls C, Zhang J, Matsuno M, Zhang Y, Yu O (2011) Stepwise increase of resveratrol biosynthesis in yeast Saccharomyces cerevisiae by metabolic engineering. Metab Eng 13:455–463

    Article  CAS  Google Scholar 

  145. Chen H, Jiang H, Morgan JA (2007) Non-natural cinnamic acid derivatives as substrates of cinnamate 4-hydroxylase. Phytochemistry 68:306–311

    Article  CAS  Google Scholar 

  146. Williams GJ, Zhang C, Thorson JS (2007) Expanding the promiscuity of a natural-product glycosyltransferase by directed evolution. Nat Chem Biol 3:657–662

    Article  CAS  Google Scholar 

  147. Felnagle EA, Chaubey A, Noey EL, Houk KN, Liao JC (2012) Engineering synthetic recursive pathways to generate non-natural small molecules. Nat Chem Biol 8:518–526

    Article  CAS  Google Scholar 

  148. Minami H, Kim J-S, Ikezawa N, Takemura T, Katayama T, Kumagai H, Sato F (2008) Microbial production of plant benzylisoquinoline alkaloids. Proc Natl Acad Sci USA 105:7393–7398

    Article  CAS  Google Scholar 

  149. Challis GL, Hopwood DA (2007) Chemical biotechnology: bioactive small molecules – targets and discovery technologies. Curr Opin Biotechnol 18:475–477

    Article  CAS  Google Scholar 

  150. Straathof AJJ, Panke S, Schmid A (2002) The production of fine chemicals by biotransformations. Curr Opin Biotechnol 13:548–556

    Article  CAS  Google Scholar 

  151. Kagami O, Shindo K, Kyojima A, Takeda K, Ikenaga H, Furukawa K, Misawa N (2008) Protein engineering on biphenyl dioxygenase for conferring activity to convert 7-hydroxyflavone and 5,7-dihydroxyflavone (chrysin). J Biosci Bioeng 106:121–127

    Article  CAS  Google Scholar 

  152. Laparra JM, Sanz Y (2010) Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res: Off J Italian pharmacol soc 61:219–225

    Article  CAS  Google Scholar 

  153. Park H-Y, Kim M, Han J (2011) Stereospecific microbial production of isoflavanones from isoflavones and isoflavone glucosides. Appl Microbiol Biotechnol 91:1173–1181

    Article  CAS  Google Scholar 

  154. van Duynhoven J, Vaughan EE, Jacobs DM, Kemperman RA, van Velzen EJJ, Gross G, Roger LC, Possemiers S, Smilde AK, Doré J, Westerhuis JA, Van de Wiele T (2011) Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci USA 108(Suppl):4531–4538

    Article  Google Scholar 

  155. Jin J-S, Zhao Y-F, Nakamura N, Akao T, Kakiuchi N, Min B-S, Hattori M (2007) Enantioselective dehydroxylation of enterodiol and enterolactone precursors by human intestinal bacteria. Biol Pharm Bull 30:2113–2119

    Article  CAS  Google Scholar 

  156. Larrosa M, González-Sarrías A, García-Conesa MT, Tomás-Barberán FA, Espín JC (2006) Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J Agric Food Chem 54:1611–1620

    Article  CAS  Google Scholar 

  157. Kim M, Kim S-I, Han J, Wang X-L, Song D-G, Kim S-U (2009) Stereospecific biotransformation of dihydrodaidzein into (3S)-equol by the human intestinal bacterium Eggerthella strain Julong 732. Appl Environ Microbiol 75:3062–3068

    Article  CAS  Google Scholar 

  158. Setchell KD (2001) Soy isoflavones – benefits and risks from nature’s selective estrogen receptor modulators (SERMs). J Am Coll Nutr 20:354S–362S; discussion 381S–383S (2001)

    CAS  Google Scholar 

  159. Basly J-P, Lavier M-CC (2005) Dietary phytoestrogens: potential selective estrogen enzyme modulators? Planta Med 71:287–294

    Article  CAS  Google Scholar 

  160. Zhao X, Li L, Wang Z (2006) Chemoprevention of breast cancer: current status and future prospects. Front biosci 11:2249–2256

    Article  CAS  Google Scholar 

  161. Ho S-M (2004) Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates. J Cell Biochem 91:491–503

    Article  CAS  Google Scholar 

  162. Bowles D, Lim E-K, Poppenberger B, Vaistij FE (2006) Glycosyltransferases of lipophilic small molecules. Annu Rev Plant Biol 57:567–597

    Article  CAS  Google Scholar 

  163. Simkhada D, Kim E, Lee HC, Sohng JK (2009) Metabolic engineering of Escherichia coli for the biological synthesis of 7-O-xylosyl naringenin. Mol Cells 28:397–401

    Article  CAS  Google Scholar 

  164. Simkhada D, Kurumbang NP, Lee HC, Sohng JK (2010) Exploration of glycosylated flavonoids from metabolically engineered E. coli. Biotechnol Bioprocess Eng 15:754–760

    Article  CAS  Google Scholar 

  165. Kurumbang NP, Liou K, Sohng JK (2010) Biosynthesis of paromamine derivatives in engineered Escherichia coli by heterologous expression. J Appl Microbiol 108:1780–1788

    Article  CAS  Google Scholar 

  166. Simkhada D, Lee HC, Sohng JK (2010) Genetic engineering approach for the production of rhamnosyl and allosyl flavonoids from Escherichia coli. Biotechnol Bioeng 107:154–162

    Article  CAS  Google Scholar 

  167. Day AJ, Cañada FJ, Díaz JC, Kroon PA, Mclauchlan R, Faulds CB, Plumb GW, Morgan MR, Williamson G (2000) Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett 468:166–170

    Article  CAS  Google Scholar 

  168. Seo J, Kang S-I, Kim M, Han J, Hur H-G (2011) Flavonoids biotransformation by bacterial non-heme dioxygenases, biphenyl and naphthalene dioxygenase. Appl Microbiol Biotechnol 91:219–228

    Article  CAS  Google Scholar 

  169. Wang A, Zhang F, Huang L, Yin X, Li H, Wang Q (2010) New progress in biocatalysis and biotransformation of flavonoids. J Med Plant Res 4:847–856

    CAS  Google Scholar 

  170. Chun H-K, Ohnishi Y, Shindo K, Misawa N, Furukawa K, Horinouchi S (2003) Biotransformation of flavone and flavanone by Streptomyces lividans cells carrying shuffled biphenyl dioxygenase genes. J Mol Catal B: Enzym 21:113–121

    Article  CAS  Google Scholar 

  171. Seeger M, González M, Cámara B, Muñoz L, Ponce E, Mejías L, Mascayano C, Vásquez Y, Sepúlveda-Boza S (2003) Biotransformation of natural and synthetic isoflavonoids by two recombinant microbial enzymes. Appl Environ Microbiol 69:5045–5050

    Article  CAS  Google Scholar 

  172. Seo J, Kang S-I, Ryu J-Y, Lee Y-J, Park KD, Kim M, Won D, Park H-Y, Ahn J-H, Chong Y, Kanaly RA, Han J, Hur H-G (2010) Location of flavone B-ring controls regioselectivity and stereoselectivity of naphthalene dioxygenase from Pseudomonas sp. strain NCIB 9816-4. Appl Microbiol Biotechnol 86:1451–1462

    Article  CAS  Google Scholar 

  173. Kim B-G, Jung B-R, Lee Y, Hur H-G, Lim Y, Ahn J-H (2006) Regiospecific flavonoid 7-O-methylation with Streptomyces avermitilis O-methyltransferase expressed in Escherichia coli. J Agric Food Chem 54:823–828

    Article  CAS  Google Scholar 

  174. Santos CNS, Koffas M, Stephanopoulos G (2011) Optimization of a heterologous pathway for the production of flavonoids from glucose. Metab Eng 13:392–400

    Article  CAS  Google Scholar 

  175. Wang Y, Chen S, Yu O (2011) Metabolic engineering of flavonoids in plants and microorganisms. Appl Microbiol Biotechnol 91:949–956

    Article  CAS  Google Scholar 

  176. Xu P, Koffas MA (2010) Metabolic engineering of Escherichia coli for biofuel production. Biofuels 1:493–504

    Article  CAS  Google Scholar 

  177. Lee SY, Park JM, Kim TY (2011) Application of metabolic flux analysis in metabolic engineering. Methods Enzymol 498:67–93. Elsevier Inc

    Article  CAS  Google Scholar 

  178. Haggart CR, Bartell JA, Saucerman JJ, Papin JA (2011) Whole-genome metabolic network reconstruction and constraint-based modeling. Methods Enzymol 500:411–433. Elsevier Inc

    Article  CAS  Google Scholar 

  179. Kim HU, Kim TY, Lee SY (2008) Metabolic flux analysis and metabolic engineering of microorganisms. Mol Biosyst 4:113–120

    Article  CAS  Google Scholar 

  180. Maertens J, Vanrolleghem PA (2010) Modeling with a view to target identification in metabolic engineering: a critical evaluation of the available tools. Biotechnol Prog 26:313–331

    CAS  Google Scholar 

  181. Medema MH, van Raaphorst R, Takano E, Breitling R (2012) Computational tools for the synthetic design of biochemical pathways. Nat Rev Microbiol 10:1–12

    Article  CAS  Google Scholar 

  182. Santos F, Boele J, Teusink B (2011) A practical guide to genome-scale metabolic models and their analysis. Methods Sys Biol 500:509–532. Elsevier Inc

    Article  CAS  Google Scholar 

  183. Alberstein M, Eisenstein M, Abeliovich H (2012) Removing allosteric feedback inhibition of tomato 4-coumarate:CoA ligase by directed evolution. Plant J 69:57–69

    Article  CAS  Google Scholar 

  184. Siddiqui MS, Thodey K, Trenchard I, Smolke CD (2012) Advancing secondary metabolite biosynthesis in yeast with synthetic biology tools. FEMS Yeast Res 12:144–170

    Article  CAS  Google Scholar 

  185. Agapakis CM, Boyle PM, Silver PA (2012) Natural strategies for the spatial optimization of metabolism in synthetic biology. Nat Chem Biol 8:527–535

    Article  CAS  Google Scholar 

  186. Boyle PM, Silver PA (2012) Parts plus pipes: synthetic biology approaches to metabolic engineering. Metabolic Eng 14:223–232

    Article  CAS  Google Scholar 

  187. Delebecque CJ, Lindner AB, Silver PA, Aldaye FA (2011) Organization of intracellular reactions with rationally designed RNA assemblies. Science (New York, N.Y.) 333:470–474

    Article  CAS  Google Scholar 

  188. Delebecque CJ, Silver PA, Lindner AB (2012) Designing and using RNA scaffolds to assemble proteins in vivo. Nature Protocols 7:1797–1807

    Article  CAS  Google Scholar 

  189. Dueber JE, Wu GC, Malmirchegini GR, Moon TS, Petzold CJ, Ullal AV, Prather KLJ, Keasling JD (2009) synthetic protein scaffolds provide modular control over metabolic flux. Online 27:5–8

    Google Scholar 

  190. Weeks A, Lund L, Raushel FM (2006) Tunneling of intermediates in enzyme-catalyzed reactions. Curr Opin Chem Biol 10:465–472

    Article  CAS  Google Scholar 

  191. Bonacci W, Teng PK, Afonso B, Niederholtmeyer H, Grob P, Silver PA (2011) Modularity of a carbon-fixing protein organelle. Proc Natl Acad Sci USA 109:478

    Article  Google Scholar 

  192. Dunlop MJ, Dossani ZY, Szmidt HL, Chu HC, Lee TS, Keasling JD, Hadi MZ, Mukhopadhyay A (2011) Engineering microbial biofuel tolerance and export using efflux pumps. Mol Syst Biol 7:487

    Article  Google Scholar 

  193. Dunlop MJ (2011) Engineering microbes for tolerance to next-generation biofuels. Biotechnol biofuels 4:32

    Article  CAS  Google Scholar 

  194. Wang M, Si T, Zhao H (2012) Biocatalyst development by directed evolution. Bioresour Technol 115:117–125

    Article  CAS  Google Scholar 

  195. Hanson AD, Pribat A, Waller JC, de Crécy-Lagard V (2010) “Unknown” proteins and “orphan” enzymes: the missing half of the engineering parts list–and how to find it. Biochem J 425:1–11

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Brady F. Cress, Robert J. Linhardt & Dr. Mattheos A. G. Koffas

Authors
  1. Brady F. Cress
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert J. Linhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dr. Mattheos A. G. Koffas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brady F. Cress .

Editor information

Editors and Affiliations

  1. Botany Department, M.L. Sukhadia University, Durga Nursery Road, Udaipur, 313001, Rajasthan, India

    Kishan Gopal Ramawat

  2. Institute of Vine and Wine Sciences, Biological-Active Plant Substances Study, University of Bordeaux, 210 Chemin de Leysotte CS 50008, Villenave d'Ornon, 33882, France

    Jean-Michel Mérillon

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Cress, B.F., Linhardt, R.J., Koffas, M.A.G. (2013). Isoflavonoid Production by Genetically Engineered Microorganisms. In: Ramawat, K., Mérillon, JM. (eds) Natural Products. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22144-6_53

Download citation

Publish with us

Policies and ethics

Search

Navigation