Engineering microbial factories for synthesis of value-added products

  • Jing Du
  • Zengyi Shao
  • Huimin ZhaoEmail author


Microorganisms have become an increasingly important platform for the production of drugs, chemicals, and biofuels from renewable resources. Advances in protein engineering, metabolic engineering, and synthetic biology enable redesigning microbial cellular networks and fine-tuning physiological capabilities, thus generating industrially viable strains for the production of natural and unnatural value-added compounds. In this review, we describe the recent progress on engineering microbial factories for synthesis of valued-added products including alkaloids, terpenoids, flavonoids, polyketides, non-ribosomal peptides, biofuels, and chemicals. Related topics on lignocellulose degradation, sugar utilization, and microbial tolerance improvement will also be discussed.


Synthetic biology Metabolic engineering Microbial synthesis Value-added products Natural products Fuels and chemicals 



We thank the National Institutes of Health (GM077596), the National Academies Keck Futures Initiative on Synthetic Biology, the Biotechnology Research and Development Consortium (BRDC) (Project 2-4-121), the British Petroleum Energy Biosciences Institute, and the National Science Foundation as part of the Center for Enabling New Technologies through Catalysis (CENTC), CHE-0650456, and the National Research Foundation of Korea (NRF) (220-2009-1-D00033) for financial support. J. Du also acknowledges both the Chia-chen Chu graduate fellowship from the School of Chemical Sciences and the Henry Drickamer Fellowship support from the Department of Chemical and Biomolecular Engineering at the University of Illinois.


  1. 1.
    Ajikumar PK, Xiao WH, Tyo KE, 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 330:70–74PubMedGoogle Scholar
  2. 2.
    Alexander DC, Rock J, Gu JQ, Mascio C, Chu M, Brian P, Baltz RH (2011) Production of novel lipopeptide antibiotics related to A54145 by Streptomyces fradiae mutants blocked in biosynthesis of modified amino acids and assignment of lptJ, lptK and lptL gene functions. J Antibiot (Tokyo) 64:79–87Google Scholar
  3. 3.
    Allen RS, Millgate AG, Chitty JA, Thisleton J, Miller JA, Fist AJ, Gerlach WL, Larkin PJ (2004) RNAi-mediated replacement of morphine with the nonnarcotic alkaloid reticuline in opium poppy. Nat Biotechnol 22:1559–1566PubMedGoogle Scholar
  4. 4.
    Alper H, Stephanopoulos G (2009) Engineering for biofuels: exploiting innate microbial capacity or importing biosynthetic potential? Nat Rev Microbiol 7:715–723PubMedGoogle Scholar
  5. 5.
    Atsumi S, Cann AF, Connor MR, Shen CR, Smith KM, Brynildsen MP, Chou KJY, Hanai T, Liao JC (2008) Metabolic engineering of Escherichia coli for 1-butanol production. Metab Eng 10:305–311PubMedGoogle Scholar
  6. 6.
    Atsumi S, Hanai T, Liao JC (2008) Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuels. Nature 451:86–89PubMedGoogle Scholar
  7. 7.
    Atsumi S, Wu TY, Eckl EM, Hawkins SD, Buelter T, Liao JC (2010) Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes. Appl Microbiol Biotechnol 85:651–657PubMedGoogle Scholar
  8. 8.
    Austin MB, Bowman ME, Ferrer JL, Schroder J, Noel JP (2004) An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases. Chem Biol 11:1179–1194PubMedGoogle Scholar
  9. 9.
    Bajwa PK, Pinel D, Martin VJJ, Trevors JT, Lee H (2010) Strain improvement of the pentose-fermenting yeast Pichia stipitis by genome shuffling. J Microbiol Methods 81:179–186PubMedGoogle Scholar
  10. 10.
    Baltz RH (2010) Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters. J Ind Microbiol Biotechnol 37:759–772PubMedGoogle Scholar
  11. 11.
    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 88:5597–5601PubMedGoogle Scholar
  12. 12.
    Beller HR, Goh EB, Keasling JD (2010) Genes involved in long-chain alkene biosynthesis in Micrococcus luteus. Appl Environ Microbiol 76:1212–1223PubMedGoogle Scholar
  13. 13.
    Boghigian BA, Pfeifer BA (2008) Current status, strategies, and potential for the metabolic engineering of heterologous polyketides in Escherichia coli. Biotechnol Lett 30:1323–1330PubMedGoogle Scholar
  14. 14.
    Bonomo J, Warnecke T, Hume P, Marizcurrena A, Gill RT (2006) A comparative study of metabolic engineering anti-metabolite tolerance in Escherichia coli. Metab Eng 8:227–239PubMedGoogle Scholar
  15. 15.
    Bozell JJ, Petersen GR (2010) Technology development for the production of biobased products from biorefinery carbohydrates-the US Department of Energy’s “Top 10” revisited. Green Chem 12:539–554Google Scholar
  16. 16.
    Bull AT, Goodfellow M, Slater JH (1992) Biodiversity as a source of innovation in biotechnology. Annu Rev Microbiol 46:219–252PubMedGoogle Scholar
  17. 17.
    Burgess CM, Smid EJ, Dv Sinderen (2009) Bacterial vitamin B2, B11 and B12 overproduction: an overview. Int J Food Microbiol 133:1–7PubMedGoogle Scholar
  18. 18.
    Butler MS (2005) Natural products to drugs: natural product derived compounds in clinical trials. Nat Prod Rep 22:162–195PubMedGoogle Scholar
  19. 19.
    Cakar ZP, Seker UOS, Tamerler C, Sonderegger M, Sauer U (2005) Evolutionary engineering of multiple-stress resistant Saccharomyces cerevisiae. FEMS Yeast Res 5:569–578PubMedGoogle Scholar
  20. 20.
    Cane DE (2010) Programming of erythromycin biosynthesis by a modular polyketide synthase. J Biol Chem 285:27517–27523PubMedGoogle Scholar
  21. 21.
    Chang MC, Eachus RA, Trieu W, Ro DK, Keasling JD (2007) Engineering Escherichia coli for production of functionalized terpenoids using plant P450 s. Nat Chem Biol 3:274–277PubMedGoogle Scholar
  22. 22.
    Chang MC, Keasling JD (2006) Production of isoprenoid pharmaceuticals by engineered microbes. Nat Chem Biol 2:674–681PubMedGoogle Scholar
  23. 23.
    Chau M, Jennewein S, Walker K, Croteau R (2004) Taxol biosynthesis: molecular cloning and characterization of a cytochrome P450 taxoid 7 beta-hydroxylase. Chem Biol 11:663–672PubMedGoogle Scholar
  24. 24.
    Christ TN, Deweese KA, Woodyer RD (2010) Directed evolution toward improved production of l-ribose from ribitol. Comb Chem High Throughput Screen 13:302–308PubMedGoogle Scholar
  25. 25.
    Connor MR, Liao JC (2008) Engineering of an Escherichia coli strain for the production of 3-methyl-1-butanol. Appl Environ Microbiol 74:5769–5775Google Scholar
  26. 26.
    Davies J (1999) Millennium bugs. Trends Cell Biol 9:M2–M5PubMedGoogle Scholar
  27. 27.
    Demain AL (2006) From natural products discovery to commercialization: a success story. J Ind Microbiol Biotechnol 33:486–495PubMedGoogle Scholar
  28. 28.
    Den Haan R, Rose SH, Lynd LR, van Zyl WH (2007) Hydrolysis and fermentation of amorphous cellulose by recombinant Saccharomyces cerevisiae. Metab Eng 9:87–94Google Scholar
  29. 29.
    Dimster-Denk D, Thorsness MK, Rine J (1994) Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae. Mol Biol Cell 5:655–665PubMedGoogle Scholar
  30. 30.
    Dong X, Quinn PJ, Wang X (2011) Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for the production of l-threonine. Biotechnol Adv 29:11–23PubMedGoogle Scholar
  31. 31.
    Du H, Huang Y, Tang Y (2010) Genetic and metabolic engineering of isoflavonoid biosynthesis. Appl Microbiol Biotechnol 86:1293–1312PubMedGoogle Scholar
  32. 32.
    Du J, Li SJ, Zhao H (2010) Discovery and characterization of novel d-xylose-specific transporters from Neurospora crassa and Pichia stipitis. Mol Biosyst 6:2150–2156PubMedGoogle Scholar
  33. 33.
    Engels B, Dahm P, Jennewein S (2008) Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards taxol (paclitaxel) production. Metab Eng 10:201–206PubMedGoogle Scholar
  34. 34.
    Fischbach MA, Walsh CT (2006) Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery, and mechanisms. Chem Rev 106:3468–3496PubMedGoogle Scholar
  35. 35.
    Forkmann G, Martens S (2001) Metabolic engineering and applications of flavonoids. Curr Opin Biotechnol 12:155–160PubMedGoogle Scholar
  36. 36.
    Fujii N, Inui T, Iwasa K, Morishige T, Sato F (2007) Knockdown of berberine bridge enzyme by RNAi accumulates (S)-reticuline and activates a silent pathway in cultured California poppy cells. Transgenic Res 16:363–375PubMedGoogle Scholar
  37. 37.
    Galazka JM, Tian CG, Beeson WT, Martinez B, Glass NL, Cate JHD (2010) Cellodextrin transport in yeast for improved biofuel production. Science 330:84–86PubMedGoogle Scholar
  38. 38.
    Galbe M, Zacchi G (2002) A review of the production of ethanol from softwood. Appl Microbiol Biotechnol 59:618–628PubMedGoogle Scholar
  39. 39.
    Gao X, Wang P, Tang Y (2010) Engineered polyketide biosynthesis and biocatalysis in Escherichia coli. Appl Microbiol Biotechnol 88:1233–1242PubMedGoogle Scholar
  40. 40.
    Gershenzon J, Dudareva N (2007) The function of terpene natural products in the natural world. Nat Chem Biol 3:408–414PubMedGoogle Scholar
  41. 41.
    Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA, Merryman C, Young L, Noskov VN, Glass JI, Venter JC, Hutchison CA III, Smith HO (2008) Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science 319:1215–1220PubMedGoogle Scholar
  42. 42.
    Gibson DG, Benders GA, Axelrod KC, Zaveri J, Algire MA, Moodie M, Montague MG, Venter JC, Smith HO, Hutchison CA III (2008) One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome. Proc Natl Acad Sci USA 105:20404–20409PubMedGoogle Scholar
  43. 43.
    Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA III, Smith HO, Venter JC (2010) Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329:52–56PubMedGoogle Scholar
  44. 44.
    Gonzalez R, Tao H, Purvis JE, York SW, Shanmugam KT, Ingram LO (2003) Gene array-based identification of changes that contribute to ethanol tolerance in ethanologenic Escherichia coli: comparison of KO11 (parent) to LY01 (resistant mutant). Biotechnol Prog 19:612–623PubMedGoogle Scholar
  45. 45.
    Ha SJ, Galazka JM, Rin Kim S, Choi JH, Yang X, Seo JH, Louise Glass N, Cate JH, Jin YS (2010) Engineered Saccharomyces cerevisiae capable of simultaneous cellobiose and xylose fermentation. Proc Natl Acad Sci USAGoogle Scholar
  46. 46.
    Hahn-Hagerdal B, Karhumaa K, Fonseca C, Spencer-Martins I, Gorwa-Grauslund MF (2007) Towards industrial pentose-fermenting yeast strains. Appl Microbiol Biotechnol 74:937–953PubMedGoogle Scholar
  47. 47.
    Hanai T, Atsumi S, Liao JC (2007) Engineered synthetic pathway for isopropanol production in Escherichia coli. Appl Environ Microbiol 73:7814–7818PubMedGoogle Scholar
  48. 48.
    Hawkins KM, Smolke CD (2008) Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae. Nat Chem Biol 4:564–573PubMedGoogle Scholar
  49. 49.
    Hector RE, Qureshi N, Hughes SR, Cotta MA (2008) Expression of a heterologous xylose transporter in a Saccharomyces cerevisiae strain engineered to utilize xylose improves aerobic xylose consumption. Appl Microbiol Biotechnol 80:675–684PubMedGoogle Scholar
  50. 50.
    Hertweck C, Luzhetskyy A, Rebets Y, Bechthold A (2007) Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork. Nat Prod Rep 24:162–190PubMedGoogle Scholar
  51. 51.
    Hill J, Nelson E, Tilman D, Polasky S, Tiffany D (2006) Environmental, economic, and energetic costs and benefits of biodiesel and ethanol biofuels. Proc Natl Acad Sci USA 103:11206–11210PubMedGoogle Scholar
  52. 52.
    Hong ME, Lee KS, Yu BJ, Sung YJ, Park SM, Koo HM, Kweon DH, Park JC, Jin YS (2010) Identification of gene targets eliciting improved alcohol tolerance in Saccharomyces cerevisiae through inverse metabolic engineering. J Biotechnol 149:52–59PubMedGoogle Scholar
  53. 53.
    Goodman J, Walsh V (2001) The story of taxol: nature and politics in the pursuit of an anti-cancer drug. Cambridge University Press, CambridgeGoogle Scholar
  54. 54.
    Jiang XL, Meng X, Xian M (2009) Biosynthetic pathways for 3-hydroxypropionic acid production. Appl Microbiol Biotechnol 82:995–1003PubMedGoogle Scholar
  55. 55.
    Julsing MK, Koulman A, Woerdenbag HJ, Quax WJ, Kayser O (2006) Combinatorial biosynthesis of medicinal plant secondary metabolites. Biomol Eng 23:265–279PubMedGoogle Scholar
  56. 56.
    Katahira S, Ito M, Takema H, Fujita Y, Tanino T, Tanaka T, Fukuda H, Kondo A (2008) Improvement of ethanol productivity during xylose and glucose co-fermentation by xylose-assimilating S. cerevisiae via expression of glucose transporter Sut1. Enzyme Microb Technol 43:115–119Google Scholar
  57. 57.
    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 14:613–621PubMedGoogle Scholar
  58. 58.
    Katsuyama Y, Hirose Y, Funa N, Ohnishi Y, Horinouchi S (2010) Precursor-directed biosynthesis of curcumin analogs in Escherichia coli. Biosci Biotechnol Biochem 74:641–645PubMedGoogle Scholar
  59. 59.
    Katsuyama Y, Matsuzawa M, Funa N, Horinouchi S (2008) Production of curcuminoids by Escherichia coli carrying an artificial biosynthesis pathway. Microbiology 154:2620–2628PubMedGoogle Scholar
  60. 60.
    Kemeny-Beke A, Aradi J, Damjanovich J, Beck Z, Facsko A, Berta A, Bodnar A (2006) Apoptotic response of uveal melanoma cells upon treatment with chelidonine, sanguinarine and chelerythrine. Cancer Lett 237:67–75PubMedGoogle Scholar
  61. 61.
    Kingston DG (2007) The shape of things to come: structural and synthetic studies of taxol and related compounds. Phytochemistry 68:1844–1854PubMedGoogle Scholar
  62. 62.
    Kong WJ, Wei J, Abidi P, Lin MH, Inaba S, Li C, Wang YL, Wang ZZ, Si SY, Pan HN, Wang SK, Wu JD, Wang Y, Li ZR, Liu JW, Jiang JD (2004) Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 10:1344–1351PubMedGoogle Scholar
  63. 63.
    Kotter P, Ciriacy M (1993) Xylose fermentation by Saccharomyces cerevisiae. Appl Microbiol Biotechnol 38:776–783Google Scholar
  64. 64.
    Kwan CY, Achike FI (2002) Tetrandrine and related bis-benzylisoquinoline alkaloids from medicinal herbs: cardiovascular effects and mechanisms of action. Acta Pharmacol Sin 23:1057–1068PubMedGoogle Scholar
  65. 65.
    Lai JH (2002) Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases. Acta Pharmacol Sin 23:1093–1101PubMedGoogle Scholar
  66. 66.
    Leadbetter JR (2003) Cultivation of recalcitrant microbes: cells are alive, well and revealing their secrets in the 21st century laboratory. Curr Opin Microbiol 6:274–281PubMedGoogle Scholar
  67. 67.
    Leandro MJ, Goncalves P, Spencer-Martins I (2006) Two glucose/xylose transporter genes from the yeast Candida intermedia: first molecular characterization of a yeast xylose-H+ symporter. Biochem J 395:543–549PubMedGoogle Scholar
  68. 68.
    Lee SJ, Song H, Lee SY (2006) Genome-based metabolic engineering of Mannheimia succiniciproducens for succinic acid production. Biochem J 72:1939–1948Google Scholar
  69. 69.
    Lee SY, Kim HU, Park JH, Park JM, Kim TY (2009) Metabolic engineering of microorganisms: general strategies and drug production. Drug Discov Today 14:78–88PubMedGoogle Scholar
  70. 70.
    Leonard E, Koffas MA (2007) Engineering of artificial plant cytochrome P450 enzymes for synthesis of isoflavones by Escherichia coli. Appl Environ Microbiol 73:7246–7251PubMedGoogle Scholar
  71. 71.
    Leonard E, Lim KH, Saw PN, Koffas MA (2007) Engineering central metabolic pathways for high-level flavonoid production in Escherichia coli. Appl Environ Microbiol 73:3877–3886PubMedGoogle Scholar
  72. 72.
    Leonard E, Nielsen D, Solomon K, Prather KJ (2008) Engineering microbes with synthetic biology frameworks. Trends Biotechnol 26:674–681PubMedGoogle Scholar
  73. 73.
    Leonard E, Runguphan W, O’Connor S, Prather KJ (2009) Opportunities in metabolic engineering to facilitate scalable alkaloid production. Nat Chem Biol 5:292–300PubMedGoogle Scholar
  74. 74.
    Leonard E, Yan Y, Fowler ZL, Li Z, Lim CG, Lim KH, Koffas MA (2008) Strain improvement of recombinant Escherichia coli for efficient production of plant flavonoids. Mol Pharm 5:257–265PubMedGoogle Scholar
  75. 75.
    Li SJ, Du J, Sun J, Galazka JM, Glass NL, Cate JHD, Yang XM, Zhao H (2010) Overcoming glucose repression in mixed sugar fermentation by co-expressing a cellobiose transporter and a beta-glucosidase in Saccharomyces cerevisiae. Mol BioSyst 6:2129–2132Google Scholar
  76. 76.
    Linger JG, Adney WS, Darzins A (2010) Heterologous expression and extracellular secretion of cellulolytic enzymes by Zymomonas mobilis. Appl Environ Microbiol 76:6360–6369PubMedGoogle Scholar
  77. 77.
    Lynd LR, Cushman JH, Nichols RJ, Wyman CE (1991) Fuel ethanol from cellulosic biomass. Science 251:1318–1323PubMedGoogle Scholar
  78. 78.
    Lynd LR, Laser MS, Brandsby D, Dale BE, Davison B, Hamilton R, Himmel M, Keller M, McMillan JD, Sheehan J, Wyman CE (2008) How biotech can transform biofuels. Nat Biotechnol 26:169–172PubMedGoogle Scholar
  79. 79.
    Lynd LR, van Zyl WH, McBride JE, Laser M (2005) Consolidated bioprocessing of cellulosic biomass: an update. Curr Opin Biotechnol 16:577–583PubMedGoogle Scholar
  80. 80.
    Matsushika A, Inoue H, Murakami K, Takimura O, Sawayama S (2009) Bioethanol production performance of five recombinant strains of laboratory and industrial xylose-fermenting Saccharomyces cerevisiae. Bioresour Technol 100:2392–2398PubMedGoogle Scholar
  81. 81.
    Mazumdar S, Clomburg JM, Gonzalez R (2010) Escherichia coli strains engineered for homofermentative production of d-lactic acid from glycerol. Appl Environ Microbiol 76:4327–4336PubMedGoogle Scholar
  82. 82.
    McDaniel R, Weiss R (2005) Advances in synthetic biology: on the path from prototypes to applications. Curr Opin Biotechnol 16:476–483PubMedGoogle Scholar
  83. 83.
    Menzella HG, Reeves CD (2007) Combinatorial biosynthesis for drug development. Curr Opin Microbiol 10:238–245PubMedGoogle Scholar
  84. 84.
    Minami H, Kim JS, Ikezawa N, Takemura T, Katayama T, Kumagai H, Sato F (2008) Microbial production of plant benzylisoquinoline alkaloids. Proc Natl Acad Sci USA 105:7393–7398PubMedGoogle Scholar
  85. 85.
    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 71:53–58PubMedGoogle Scholar
  86. 86.
    Moon TS, Dueber JE, Shiue E, Prather KLJ (2010) Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli. Metab Eng 12:298–305PubMedGoogle Scholar
  87. 87.
    Moon TS, Yoon SH, Lanza AM, Roy-Mayhew JD, Prather KLJ (2009) Production of glucaric acid from a synthetic pathway in recombinant Escherichia coli. Appl Environ Microbiol 75:589–595PubMedGoogle Scholar
  88. 88.
    Muntendam R, Melillo E, Ryden A, Kayser O (2009) Perspectives and limits of engineering the isoprenoid metabolism in heterologous hosts. Appl Microbiol Biotechnol 84:1003–1019PubMedGoogle Scholar
  89. 89.
    Mutka SC, Bondi SM, Carney JR, Da Silva NA, Kealey JT (2006) Metabolic pathway engineering for complex polyketide biosynthesis in Saccharomyces cerevisiae. FEMS Yeast Res 6:40–47PubMedGoogle Scholar
  90. 90.
    Mutka SC, Carney JR, Liu Y, Kennedy J (2006) Heterologous production of epothilone C and D in Escherichia coli. Biochemistry 45:1321–1330PubMedGoogle Scholar
  91. 91.
    Nair NU, Zhao H (2008) Evolution in reverse: engineering a d-xylose-specific xylose reductase. ChemBioChem 9:1213–1215PubMedGoogle Scholar
  92. 92.
    Nair NU, Zhao H (2010) Selective reduction of xylose to xylitol from a mixture of hemicellulosic sugars. Metab Eng 12:462–468PubMedGoogle Scholar
  93. 93.
    Nakamura CE, Whited GM (2003) Metabolic engineering for the microbial production of 1, 3-propanediol. Curr Opin Biotechnol 14:454–459PubMedGoogle Scholar
  94. 94.
    Nguyen KT, He X, Alexander DC, Li C, Gu JQ, Mascio C, Van Praagh A, Mortin L, Chu M, Silverman JA, Brian P, Baltz RH (2010) Genetically engineered lipopeptide antibiotics related to A54145 and daptomycin with improved properties. Antimicrob Agents Chemother 54:1404–1413PubMedGoogle Scholar
  95. 95.
    Nguyen KT, Ritz D, Gu JQ, Alexander D, Chu M, Miao V, Brian P, Baltz RH (2006) Combinatorial biosynthesis of novel antibiotics related to daptomycin. Proc Natl Acad Sci USA 103:17462–17467PubMedGoogle Scholar
  96. 96.
    Nicolaou KC, Yang Z, Liu JJ, Ueno H, Nantermet PG, Guy RK, Claiborne CF, Renaud J, Couladouros EA, Paulvannan K et al (1994) Total synthesis of taxol. Nature 367:630–634PubMedGoogle Scholar
  97. 97.
    Olano C, Mendez C, Salas JA (2009) Antitumor compounds from actinomycetes: from gene clusters to new derivatives by combinatorial biosynthesis. Nat Prod Rep 26:628–660PubMedGoogle Scholar
  98. 98.
    Olano C, Mendez C, Salas JA (2010) Post-PKS tailoring steps in natural product-producing actinomycetes from the perspective of combinatorial biosynthesis. Nat Prod Rep 27:571–616PubMedGoogle Scholar
  99. 99.
    Pfeifer BA, Admiraal SJ, Gramajo H, Cane DE, Khosla C (2001) Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli. Science 291:1790–1792PubMedGoogle Scholar
  100. 100.
    Holton RA, Biediger RJ, Boatman PD (1995) Taxol: science and applications. CRC, Boca RatonGoogle Scholar
  101. 101.
    Raab AM, Gebhardt G, Bolotina N, Weuster-Botz D, Lang C (2010) Metabolic engineering of Saccharomyces cerevisiae for the biotechnological production of succinic acid. Metab Eng 12:518–525PubMedGoogle Scholar
  102. 102.
    Rao Z, Ma Z, Shen W, Fang H, Zhuge J, Wang X (2008) Engineered Saccharomyces cerevisiae that produces 1, 3-propanediol from d-glucose. J Appl Microbiol 105:1768–1776PubMedGoogle Scholar
  103. 103.
    Rathnasingh C, Raj SM, Jo JE, Park S (2009) Development and evaluation of efficient recombinant Escherichia coli strains for the production of 3-hydroxypropionic acid from glycerol. Biotechnol Bioeng 104:729–739PubMedGoogle Scholar
  104. 104.
    Ro DK, Ouellet M, Paradise EM, Burd H, Eng D, Paddon CJ, Newman JD, Keasling JD (2008) Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malarial drug precursor, artemisinic acid. BMC Biotechnol 8:83PubMedGoogle Scholar
  105. 105.
    Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MC, Withers ST, Shiba Y, Sarpong R, Keasling JD (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940–943PubMedGoogle Scholar
  106. 106.
    Roberts SC (2007) Production and engineering of terpenoids in plant cell culture. Nat Chem Biol 3:387–395PubMedGoogle Scholar
  107. 107.
    Roca C, Haack MB, Olsson L (2004) Engineering of carbon catabolite repression in recombinant xylose fermenting Saccharomyces cerevisiae. Appl Microbiol Biotechnol 63:578–583PubMedGoogle Scholar
  108. 108.
    Runquist D, Fonseca C, Radstrom P, Spencer-Martins I, Hahn-Hagerdal B (2009) Expression of the Gxf1 transporter from Candida intermedia improves fermentation performance in recombinant xylose-utilizing Saccharomyces cerevisiae. Appl Microbiol Biotechnol 82:123–130PubMedGoogle Scholar
  109. 109.
    Runquist D, Hahn-Hagerdal B, Bettiga M (2010) Increased ethanol productivity in xylose-utilizing Saccharomyces cerevisiae via a randomly mutagenized xylose reductase. Appl Environ Microbiol 76:7796–7802PubMedGoogle Scholar
  110. 110.
    Rutherford BJ, Dahl RH, Price RE, Szmidt HL, Benke PI, Mukhopadhyay A, Keasling JD (2010) Functional genomic study of exogenous n-butanol stress in Escherichia coli. Appl Environ Microbiol 76:1935–1945PubMedGoogle Scholar
  111. 111.
    Saha BC (2003) Hemicellulose bioconversion. J Ind Microbiol Biotechnol 30:279–291PubMedGoogle Scholar
  112. 112.
    Sanchez AM, Bennett GN, San KY (2005) Efficient succinic acid production from glucose through overexpression of pyruvate carboxylase in an Escherichia coli alcohol dehydrogenase and lactate dehydrogenase mutant. Biotechnol Prog 21:358–365PubMedGoogle Scholar
  113. 113.
    Sanchez C, Mendez C, Salas JA (2006) Engineering biosynthetic pathways to generate antitumor indolocarbazole derivatives. J Ind Microbiol Biotechnol 33:560–568PubMedGoogle Scholar
  114. 114.
    Sanchez C, Salas AP, Brana AF, Palomino M, Pineda-Lucena A, Carbajo RJ, Mendez C, Moris F, Salas JA (2009) Generation of potent and selective kinase inhibitors by combinatorial biosynthesis of glycosylated indolocarbazoles. Chem Commun (Camb):4118–4120Google Scholar
  115. 115.
    Sato F, Hashimoto T, Hachiya A, Tamura K, Choi KB, Morishige T, Fujimoto H, Yamada Y (2001) Metabolic engineering of plant alkaloid biosynthesis. Proc Natl Acad Sci USA 98:367–372PubMedGoogle Scholar
  116. 116.
    Sato F, Inui T, Takemura T (2007) Metabolic engineering in isoquinoline alkaloid biosynthesis. Curr Pharm Biotechnol 8:211–218PubMedGoogle Scholar
  117. 117.
    Schafer H, Wink M (2009) Medicinally important secondary metabolites in recombinant microorganisms or plants: progress in alkaloid biosynthesis. Biotechnol J 4:1684–1703PubMedGoogle Scholar
  118. 118.
    Schirmer A, Rude MA, Li XZ, Popova E, del Cardayre SB (2010) Microbial biosynthesis of alkanes. Science 329:559–562PubMedGoogle Scholar
  119. 119.
    Sevrioukova IF, Li H, Zhang H, Peterson JA, Poulos TL (1999) Structure of a cytochrome P450-redox partner electron-transfer complex. Proc Natl Acad Sci USA 96:1863–1868PubMedGoogle Scholar
  120. 120.
    Shao Z, Luo Y, Zhao H (2011) Rapid characterization and engineering of natural product biosynthetic pathways via DNA assembler. Mol BioSyst (in press)Google Scholar
  121. 121.
    Shao Z, Zhao H, Zhao H (2009) DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Res 37:e16PubMedGoogle Scholar
  122. 122.
    Sieber SA, Marahiel MA (2005) Molecular mechanisms underlying nonribosomal peptide synthesis: approaches to new antibiotics. Chem Rev 105:715–738PubMedGoogle Scholar
  123. 123.
    Siewers V, Chen X, Huang L, Zhang J, Nielsen J (2009) Heterologous production of non-ribosomal peptide LLD-ACV in Saccharomyces cerevisiae. Metab Eng 11:391–397PubMedGoogle Scholar
  124. 124.
    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 28:397–401PubMedGoogle Scholar
  125. 125.
    Singhvi M, Joshi D, Adsul M, Varma A, Gokhale D (2010) d-(-)-Lactic acid production from cellobiose and cellulose by Lactobacillus lactis mutant RM2-24. Green Chem 12:1106–1109Google Scholar
  126. 126.
    Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416PubMedGoogle Scholar
  127. 127.
    Steen EJ, Chan R, Prasad N, Myers S, Petzold CJ, Redding A, Ouellet M, Keasling JD (2008) Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol. Microb Cell Fact 7:36–43PubMedGoogle Scholar
  128. 128.
    Steen EJ, Kang YS, Bokinsky G, Hu ZH, Schirmer A, McClure A, del Cardayre SB, Keasling JD (2010) Microbial production of fatty-acid-derived fuels and chemicals from plant biomass. Nature 463:559–562PubMedGoogle Scholar
  129. 129.
    Tang XM, Tan YS, Zhu H, Zhao K, Shen W (2009) Microbial conversion of glycerol to 1, 3-propanediol by an engineered strain of Escherichia coli. Appl Environ Microbiol 75:1628–1634PubMedGoogle Scholar
  130. 130.
    Tatarko M, Romeo T (2001) Disruption of a global regulatory gene to enhance central carbon flux into phenylalanine biosynthesis in Escherichia coli. Curr Microbiol 43:26–32PubMedGoogle Scholar
  131. 131.
    Tsai SL, Goyal G, Chen W (2010) Surface display of a functional minicellulosome by intracellular complementation using a synthetic yeast consortium and its application to cellulose hydrolysis and ethanol production. Appl Environ Microbiol 76:7514–7520PubMedGoogle Scholar
  132. 132.
    Turnbull JJ, Nakajima J, Welford RW, 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 279:1206–1216PubMedGoogle Scholar
  133. 133.
    van Zyl WH, Lynd LR, den Haan R, McBride JE (2007) Consolidated bioprocessing for bioethanol production using Saccharomyces cerevisiae. In: Biofuels, vol 108. Advances in biochemical engineering/biotechnology. Springer, Berlin Heidelberg New York, pp 205–235Google Scholar
  134. 134.
    Walker GM (1998) Yeast physiology and biotechnology. Wiley, New YorkGoogle Scholar
  135. 135.
    Wang Y, Boghigian BA, Pfeifer BA (2007) Improving heterologous polyketide production in Escherichia coli by overexpression of an S-adenosylmethionine synthetase gene. Appl Microbiol Biotechnol 77:367–373PubMedGoogle Scholar
  136. 136.
    Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93:2325–2327PubMedGoogle Scholar
  137. 137.
    Weisshaar B, Jenkins GI (1998) Phenylpropanoid biosynthesis and its regulation. Curr Opin Plant Biol 1:251–257PubMedGoogle Scholar
  138. 138.
    Weissman KJ, Leadlay PF (2005) Combinatorial biosynthesis of reduced polyketides. Nat Rev Microbiol 3:925–936PubMedGoogle Scholar
  139. 139.
    Wen F, Nair NU, Zhao H (2009) Protein engineering in designing tailored enzymes and microorganisms for biofuels production. Curr Opin Biotechnol 20:412–419PubMedGoogle Scholar
  140. 140.
    Wen F, Sun J, Zhao H (2010) Yeast surface display of trifunctional minicellulosomes for simultaneous saccharification and fermentation of cellulose to ethanol. Appl Environ Microbiol 76:1251–1260PubMedGoogle Scholar
  141. 141.
    Williams PA, Cosme J, Sridhar V, Johnson EF, McRee DE (2000) Microsomal cytochrome P450 2C5: comparison to microbial P450 s and unique features. J Inorg Biochem 81:183–190PubMedGoogle Scholar
  142. 142.
    Woodyer RD, Wymer NJ, Racine FM, Khan SN, Saha BC (2008) Efficient production of l-ribose with a recombinant Escherichia coli biocatalyst. Appl Environ Microbiol 74:2967–2975PubMedGoogle Scholar
  143. 143.
    Yakandawala N, Romeo T, Friesen AD, Madhyastha S (2008) Metabolic engineering of Escherichia coli to enhance phenylalanine production. Appl Microbiol Biotechnol 78:283–291PubMedGoogle Scholar
  144. 144.
    Yan Y, Huang L, Koffas MA (2007) Biosynthesis of 5-deoxyflavanones in microorganisms. Biotechnol J 2:1250–1262PubMedGoogle Scholar
  145. 145.
    Yan Y, Liao JC (2009) Engineering metabolic systems for production of advanced fuels. J Ind Microbiol Biotechnol 36:471–479PubMedGoogle Scholar
  146. 146.
    Yang SH, Pelletier DA, Lu TYS, Brown SD (2010) The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors. BMC Biotechnol 10:11Google Scholar
  147. 147.
    Zhang H, Boghigian BA, Pfeifer BA (2010) Investigating the role of native propionyl-CoA and methylmalonyl-CoA metabolism on heterologous polyketide production in Escherichia coli. Biotechnol Bioeng 105:567–573PubMedGoogle Scholar
  148. 148.
    Zhang W, Li Y, Tang Y (2008) Engineered biosynthesis of bacterial aromatic polyketides in Escherichia coli. Proc Natl Acad Sci USA 105:20683–20688PubMedGoogle Scholar
  149. 149.
    Zhang XM, Li Y, Zhuge B, Tang XM, Shen W, Rao ZM, Fang HY, Zhuge J (2006) Construction of a novel recombinant Escherichia coli strain capable of producing 1, 3-propanediol and optimization of fermentation parameters by statistical design. World J Microbiol Biotechnol 22:945–952Google Scholar
  150. 150.
    Zulak KG, Cornish A, Daskalchuk TE, Deyholos MK, Goodenowe DB, Gordon PM, Klassen D, Pelcher LE, Sensen CW, Facchini PJ (2007) Gene transcript and metabolite profiling of elicitor-induced opium poppy cell cultures reveals the coordinate regulation of primary and secondary metabolism. Planta 225:1085–1106PubMedGoogle Scholar

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© Society for Industrial Microbiology 2011

Authors and Affiliations

  1. 1.Department of Chemical and Biomolecular EngineeringUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Departments of Chemistry and Biochemistry, Institute of Genomic BiologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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