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Biosynthesis-based artificial evolution of microbial natural products

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Abstract

Natural products are often secondary metabolites in living organisms with a wide variety of biological activities. The diversification of their structures, aiming to the search for biologically active small molecules by expanding chemical and functional spaces, is a major area of current interest in synthetic chemistry. However, developing synthetic accessibility and efficiency often faces challenges associated with structural complexity. Synthetic biology has recently emerged and is promising to accomplish complex molecules; by contrast, the application to structural diversification of natural products relies on the understanding, development and utilization of compatible biosynthetic machinery. Here, we review the strategies primarily concerning the artificial evolution of microbial natural products whose biosynthesis features template enzymology, including ribosomally synthesized and post-translationally modified peptides as well as the assembly line-resultant polyketides, non-ribosomal peptides and hybrids. The establishment of these approaches largely facilitates the expansion of the molecular diversity and utility through bioengineering at different stages/levels of biosynthetic pathways.

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References

  1. Newman DJ, Cragg GM. J Nat Prod, 2012, 75: 311–335

    Article  CAS  Google Scholar 

  2. Koehn FE, Carter GT. Nat Rev Drug Discov, 2005, 4: 206–220

    Article  CAS  Google Scholar 

  3. Robles O, Romo D. Nat Prod Rep, 2014, 31: 318–334

    Article  CAS  Google Scholar 

  4. Postnikova GS, Rabinovich MS, Braginskaya PS. Pharm Chem J, 1968, 2: 34–38

    Article  Google Scholar 

  5. Morimoto S, Takahashi Y, Watanabe Y, Omura S. J Antibiot, 1984, 37: 187–189

    Article  CAS  Google Scholar 

  6. Klayman D. Science, 1985, 228: 1049–1055

    Article  CAS  Google Scholar 

  7. Huang K, Xia L, Zhang Y, Ding X, Zahn JA. Appl Microbiol Biotechnol, 2009, 82: 13–23

    Article  CAS  Google Scholar 

  8. Baltz RH. Nat Biotechnol, 2006, 24: 1533–1540

    Article  CAS  Google Scholar 

  9. Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD, Craik DJ, Dawson M, Dittmann E, Donadio S, Dorrestein PC, Entian KD, Fischbach MA, Garavelli JS, Göransson U, Gruber CW, Haft DH, Hemscheidt TK, Hertweck C, Hill C, Horswill AR, Jaspars M, Kelly WL, Klinman JP, Kuipers OP, Link AJ, Liu W, Marahiel MA, Mitchell DA, Moll GN, Moore BS, Müller R, Nair SK, Nes IF, Norris GE, Olivera BM, Onaka H, Patchett ML, Piel J, Reaney MJT, Rebuffat S, Ross RP, Sahl HG, Schmidt EW, Selsted ME, Severinov K, Shen B, Sivonen K, Smith L, Stein T, Süssmuth RD, Tagg JR, Tang GL, Truman AW, Vederas JC, Walsh CT, Walton JD, Wenzel SC, Willey JM, van der Donk WA. Nat Prod Rep, 2013, 30: 108–160

    Article  CAS  Google Scholar 

  10. Huo L, Rachid S, Stadler M, Wenzel SC, Müller R. Chem Biol, 2012, 19: 1278–1287

    Article  CAS  Google Scholar 

  11. Burkhart BJ, Hudson GA, Dunbar KL, Mitchell DA. Nat Chem Biol, 2015, 11: 564–570

    Article  CAS  Google Scholar 

  12. Zhang Q, Liu W. Nat Prod Rep, 2013, 30: 218–226

    Article  CAS  Google Scholar 

  13. Li J, Qu X, He X, Duan L, Wu G, Bi D, Deng Z, Liu W, Ou HY, Zhang R. PLoS ONE, 2012, 7: e45878

    Google Scholar 

  14. Wang S, Zhou S, Liu W. Curr Opin Chem Biol, 2013, 17: 626–634

    Article  CAS  Google Scholar 

  15. Acker MG, Bowers AA, Walsh CT. J Am Chem Soc, 2009, 131: 17563–17565

    Article  CAS  Google Scholar 

  16. Bowers AA, Acker MG, Koglin A, Walsh CT. J Am Chem Soc, 2010, 132: 7519–7527

    Article  CAS  Google Scholar 

  17. Young TS, Walsh CT. Proc Natl Acad Sci, 2011, 108: 13053–13058

    Article  CAS  Google Scholar 

  18. Li C, Zhang F, Kelly WL. Mol BioSyst, 2011, 7: 82–90

    Article  CAS  Google Scholar 

  19. Li C, Zhang F, Kelly WL. Chem Commun, 2012, 48: 558–560

    Article  CAS  Google Scholar 

  20. Zhang F, Kelly WL. ACS Chem Biol, 2015, 10: 998–1009

    Article  CAS  Google Scholar 

  21. Maksimov MO, Pan SJ, James Link A. Nat Prod Rep, 2012, 29: 996–1006

    Article  CAS  Google Scholar 

  22. Young TS, Dorrestein PC, Walsh CT. Chem Biol, 2012, 19: 1600–1610

    Article  CAS  Google Scholar 

  23. Bowers AA, Acker MG, Young TS, Walsh CT. J Am Chem Soc, 2012, 134: 10313–10316

    Article  CAS  Google Scholar 

  24. Liao R, Liu W. J Am Chem Soc, 2011, 133: 2852–2855

    Article  CAS  Google Scholar 

  25. Yu Y, Guo H, Zhang Q, Duan L, Ding Y, Liao R, Lei C, Shen B, Liu W. J Am Chem Soc, 2010, 132: 16324–16326

    Article  CAS  Google Scholar 

  26. Yu Y, Duan L, Zhang Q, Liao R, Ding Y, Pan H, Wendt-Pienkowski E, Tang G, Shen B, Liu W. ACS Chem Biol, 2009, 4: 855–864

    Article  CAS  Google Scholar 

  27. Bowers AA, Walsh CT, Acker MG. J Am Chem Soc, 2010, 132: 12182–12184

    Article  CAS  Google Scholar 

  28. Duan L, Wang S, Liao R, Liu W. Chem Biol, 2012, 19: 443–448

    Article  CAS  Google Scholar 

  29. Zhang Q, Li Y, Chen D, Yu Y, Duan L, Shen B, Liu W. Nat Chem Biol, 2011, 7: 154–160

    Article  CAS  Google Scholar 

  30. Zheng Q, Wang S, Liu W. Tetrahedron, 2014, 70: 7686–7690

    Article  CAS  Google Scholar 

  31. Zheng Q, Wang Q, Wang S, Wu J, Gao Q, Liu W. Chem Biol, 2015, 22: 1002–1007

    Article  CAS  Google Scholar 

  32. Wang S, Zheng Q, Wang J, Zhao Z, Li Q, Yu Y, Wang R, Liu W. Org Chem Front, 2015, 2: 106–109

    Article  CAS  Google Scholar 

  33. Fischbach MA, Walsh CT. Chem Rev, 2006, 106: 3468–3496

    Article  CAS  Google Scholar 

  34. Hertweck C. Angew Chem Int Ed, 2009, 48: 4688–4716

    Article  CAS  Google Scholar 

  35. Sieber SA, Marahiel MA. Chem Rev, 2005, 105: 715–738

    Article  CAS  Google Scholar 

  36. Walsh CT. Science, 2004, 303: 1805–1810

    Article  CAS  Google Scholar 

  37. Cortes J, Haydock SF, Roberts GA, Bevitt DJ, Leadlay PF. Nature, 1990, 348: 176–178

    Article  CAS  Google Scholar 

  38. Staunton J, Wilkinson B. Chem Rev, 1997, 97: 2611–2630

    Article  CAS  Google Scholar 

  39. Donadio S, McAlpine JB, Sheldon PJ, Jackson M, Katz L. Proc Natl Acad Sci, 1993, 90: 7119–7123

    Article  CAS  Google Scholar 

  40. Reid R, Piagentini M, Rodriguez E, Ashley G, Viswanathan N, Carney J, Santi DV, Hutchinson CR, McDaniel R. Biochemistry, 2003, 42: 72–79

    Article  CAS  Google Scholar 

  41. Bevitt DJ, Staunton J, Leadlay PF. Biochem Soc Trans, 1993, 21: 30S–30S

    Article  CAS  Google Scholar 

  42. McDaniel R, Thamchaipenet A, Gustafsson C, Fu H, Betlach M, Betlach M, Ashley G. Proc Natl Acad Sci, 1999, 96: 1846–1851

    Article  CAS  Google Scholar 

  43. Ruan X, Pereda A, Stassi DL, Zeidner D, Summers RG, Jackson M, Shivakumar A, Kakavas S, Staver MJ, Donadio S, Katz L. J Bacteriol, 1997, 179: 6416–6425

    CAS  Google Scholar 

  44. Petkovic H, Lill RE, Sheridan RM, Wilkinson B, McCORMICK EL, McARTHUR HAI, Staunton J, Leadlay PF, Kendrew SG. J Antibiot, 2003, 56: 543–551

    Article  CAS  Google Scholar 

  45. Liu L, Thamchaipenet A, Fu H, Betlach M, Ashley G. J Am Chem Soc, 1997, 119: 10553–10554

    Article  CAS  Google Scholar 

  46. Stassi DL, Kakavas SJ, Reynolds KA, Gunawardana G, Swanson S, Zeidner D, Jackson M, Liu H, Buko A, Katz L. Proc Natl Acad Sci, 1998, 95: 7305–7309

    Article  CAS  Google Scholar 

  47. Ridley CP, Lee HY, Khosla C. Proc Natl Acad Sci, 2008, 105: 4595–4600

    Article  CAS  Google Scholar 

  48. Reeves CD, Murli S, Ashley GW, Piagentini M, Hutchinson CR, McDaniel R. Biochemistry, 2001, 40: 15464–15470

    Article  CAS  Google Scholar 

  49. Bravo-Rodriguez K, Ismail-Ali AF, Klopries S, Kushnir S, Ismail S, Fansa EK, Wittinghofer A, Schulz F, Sanchez-Garcia E. ChemBioChem, 2014, 15: 1991–1997

    Article  CAS  Google Scholar 

  50. Kao CM, Luo G, Katz L, Cane DE, Khosla C. J Am Chem Soc, 1994, 116: 11612–11613

    Article  CAS  Google Scholar 

  51. Jacobsen JR, Cane DE, Khosla C. Biochemistry, 1998, 37: 4928–4934

    Article  CAS  Google Scholar 

  52. Kao CM, Luo G, Katz L, Cane DE, Khosla C. J Am Chem Soc, 1995, 117: 9105–9106

    Article  Google Scholar 

  53. Marsden AF. Science, 1998, 279: 199–202

    Article  CAS  Google Scholar 

  54. Pacey MS, Dirlam JP, Geldart RW, Leadlay PF, Mcarthur HAI, Mccormick EL, Monday RA, O’connell TN, Staunton J, Winchester TJ. J Antibiot, 1998, 51: 1029–1034

    Article  CAS  Google Scholar 

  55. Gokhale RS. Science, 1999, 284: 482–485

    Article  CAS  Google Scholar 

  56. McDaniel R, Kao CM, Hwang SJ, Khosla C. Chem Biol, 1997, 4: 667–674

    Article  CAS  Google Scholar 

  57. Rowe CJ, Böhm IU, Thomas IP, Wilkinson B, Rudd BAM, Foster G, Blackaby AP, Sidebottom PJ, Roddis Y, Buss AD, Staunton J, Leadlay PF. Chem Biol, 2001, 8: 475–485

    Article  CAS  Google Scholar 

  58. Thomas I, Martin CJ, Wilkinson CJ, Staunton J, Leadlay PF. Chem Biol, 2002, 9: 781–787

    Article  CAS  Google Scholar 

  59. Broadhurst RW, Nietlispach D, Wheatcroft MP, Leadlay PF, Weissman KJ. Chem Biol, 2003, 10: 723–731

    Article  CAS  Google Scholar 

  60. Tang L, Fu H, McDaniel R. Chem Biol, 2000, 7: 77–84

    Article  CAS  Google Scholar 

  61. Kim BS, Cropp TA, Florova G, Lindsay Y, Sherman DH, Reynolds KA. Biochem, 2002, 41: 10827–10833

    Article  CAS  Google Scholar 

  62. Watanabe K, Wang CCC, Boddy CN, Cane DE, Khosla C. J Biol Chem, 2003, 278: 42020–42026

    Article  CAS  Google Scholar 

  63. McDaniel R, Welch M, Hutchinson CR. Chem Rev, 2005, 105: 543–558

    Article  CAS  Google Scholar 

  64. Ray L, Moore BS. Nat Prod Rep, 2016, 33: 150–161

    Article  CAS  Google Scholar 

  65. Wilkinson B, Micklefield J. Biosynthesis of nonribosomal peptide precursors. In: Hopwood DA, Ed. Methods in Enzymology: Complex Enzymes in Microbial Natural Product Biosynthesis. Part A: Overview Articles and Peptides. San Diego: Elsevier Academic Press Inc., 2009. 353–378

    Chapter  Google Scholar 

  66. Motamedi H, Shafiee A. Eur J Biochem, 1998, 256: 528–534

    Article  CAS  Google Scholar 

  67. Schwecke T, Aparicio JF, Molnar I, Konig A, Khaw LE, Haydock SF, Oliynyk M, Caffrey P, Cortes J, Lester JB. Proc Natl Acad Sci, 1995, 92: 7839–7843

    Article  CAS  Google Scholar 

  68. Wu K, Chung L, Revill WP, Katz L, Reeves CD. Gene, 2000, 251: 81–90

    Article  CAS  Google Scholar 

  69. Andexer JN, Kendrew SG, Nur-e-Alam M, Lazos O, Foster TA, Zimmermann AS, Warneck TD, Suthar D, Coates NJ, Koehn FE, Skotnicki JS, Carter GT, Gregory MA, Martin CJ, Moss SJ, Leadlay PF, Wilkinson B. Proc Natl Acad Sci, 2011, 108: 4776–4781

    Article  CAS  Google Scholar 

  70. Mo SJ, Kim DH, Lee JH, Park JW, Basnet DB, Ban YH, Yoo YJ, Chen S, Park SR, Choi EA, Kim E, Jin YY, Lee SK, Park JY, Liu Y, Lee MO, Lee KS, Kim SJ, Kim D, Park BC, Lee S, Kwon HJ, Suh JW, Moore BS, Lim SK, Yoon YJ. J Am Chem Soc, 2011, 133: 976–985

    Article  CAS  Google Scholar 

  71. Chan YA, Boyne MT, Podevels AM, Klimowicz AK, Handelsman J, Kelleher NL, Thomas MG. Proc Natl Acad Sci, 2006, 103: 14349–14354

    Article  CAS  Google Scholar 

  72. Gatto, GJ, Boyne MT, Kelleher NL, Walsh CT. J Am Chem Soc, 2006, 128: 3838–3847

    Article  CAS  Google Scholar 

  73. Chen D, Cen P, Liu W, Xu Z. Chin J Org Chem, 2013, 33: 1254–1262

    Article  CAS  Google Scholar 

  74. Kim DH, Ryu JH, Lee KS, Lee BM, Lee MO, Lim SK, Maeng PJ. Appl Microbiol Biotechnol, 2013, 97: 5881–5892

    Article  CAS  Google Scholar 

  75. Goss RJM, Lanceron S, Deb Roy A, Sprague S, Nur-e-Alam M, Hughes DL, Wilkinson B, Moss SJ. Chem Eur J Chem Bio, 2010, 11: 698–702

    Article  CAS  Google Scholar 

  76. Goss RJM, Lanceron SE, Wise NJ, Moss SJ. Org Biomol Chem, 2006, 4: 4071–4073

    Article  CAS  Google Scholar 

  77. Ban YH, Lee JH, Gu GR, Lee B, Mo SJ, Kwon HJ, Yoon YJ. Mol BioSyst, 2013, 9: 944–947

    Article  CAS  Google Scholar 

  78. Khaw LE, Bohm GA, Metcalfe S, Staunton J, Leadlay PF. J Bacteriol, 1998, 180: 809–814

    CAS  Google Scholar 

  79. Chen D, Zhang Q, Zhang Q, Cen P, Xu Z, Liu W. Appl Environ Microbiol, 2012, 78: 5093–5103

    Article  CAS  Google Scholar 

  80. Kosec G, Goranovič D, Mrak P, Fujs, Kuščer E, Horvat J, Kopitar G, Petković H. Metabolic Eng, 2012, 14: 39–46

    Article  CAS  Google Scholar 

  81. Lechner A, Wilson MC, Ban YH, Hwang J, Yoon YJ, Moore BS. ACS Synth Biol, 2013, 2: 379–383

    Article  CAS  Google Scholar 

  82. Wilson MC, Moore BS. Nat Prod Rep, 2012, 29: 72–86

    Article  CAS  Google Scholar 

  83. Yan Y, Chen J, Zhang L, Zheng Q, Han Y, Zhang H, Zhang D, Awakawa T, Abe I, Liu W. Angew Chem Int Ed, 2013, 52: 12308–12312

    Article  CAS  Google Scholar 

  84. Zhang L, Chen J, Mori T, Yan Y, Liu W, Abe I. Acta Crystlogr F Struct Biol Commun, 2014, 70: 734–737

    Article  CAS  Google Scholar 

  85. Zhang L, Mori T, Zheng Q, Awakawa T, Yan Y, Liu W, Abe I. Angew Chem Int Ed, 2015, 54: 13462–13465

    Article  CAS  Google Scholar 

  86. Olano C, Méndez C, Salas JA. Nat Prod Rep, 2010, 27: 571–616

    Article  CAS  Google Scholar 

  87. Li TL, Liu YC, Lyu SY. Curr Opin Chem Biol, 2012, 16: 170–178

    Article  CAS  Google Scholar 

  88. Zhang C. Science, 2006, 313: 1291–1294

    Article  CAS  Google Scholar 

  89. Gantt RW, Peltier-Pain P, Cournoyer WJ, Thorson JS. Nat Chem Biol, 2011, 7: 685–691

    Article  CAS  Google Scholar 

  90. Park SR, Park JW, Ban YH, Sohng JK, Yoon YJ. Nat Prod Rep, 2013, 30: 11–20

    Article  CAS  Google Scholar 

  91. Kirby J, Keasling JD. Nat Prod Rep, 2008, 25: 656–661

    Article  CAS  Google Scholar 

  92. Xu W, Gavia DJ, Tang Y. Nat Prod Rep, 2014, 31: 1474–1487

    Article  CAS  Google Scholar 

  93. Green KD, Chen W, Houghton JL, Fridman M, Garneau-Tsodikova S. Chem Eur J Chem Bio, 2010, 11: 119–126

    Article  CAS  Google Scholar 

  94. Llewellyn NM, Spencer JB. Chem Commun, 2008, 3786

    Google Scholar 

  95. Christianson DW. Curr Opin Chem Biol, 2008, 12: 141–150

    Article  CAS  Google Scholar 

  96. Yin YC, Yu HL, Luan ZJ, Li RJ, Ouyang PF, Liu J, Xu JH. ChemBioChem, 2014, 15: 2443–2449

    Article  CAS  Google Scholar 

  97. Vedula LS, Jiang J, Zakharian T, Cane DE, Christianson DW. Arch Biochem Biophys, 2008, 469: 184–194

    Article  CAS  Google Scholar 

  98. Vedula LS, Zhao Y, Coates RM, Koyama T, Cane DE, Christianson DW. Archives Biochem Biophys, 2007, 466: 260–266

    Article  CAS  Google Scholar 

  99. Hammer SC, Marjanovic A, Dominicus JM, Nestl BM, Hauer B. Nat Chem Biol, 2015, 11: 121–126

    Article  CAS  Google Scholar 

  100. Evans BS, Chen Y, Metcalf WW, Zhao H, Kelleher NL. Chem Biol, 2011, 18: 601–607

    Article  CAS  Google Scholar 

  101. Kim E, Moore BS, Yoon YJ. Nat Chem Biol, 2015, 11: 649–659

    Article  CAS  Google Scholar 

  102. Staunton J, Wilkinson B. Curr Opin Chem Biol, 2001, 5: 159–164

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China

    Zhi Lin & Wen Liu

  2. Huzhou Center of Bio-Synthetic Innovation, Huzhou, 313000, China

    Dandan Chen & Wen Liu

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  1. Zhi Lin
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  2. Dandan Chen
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  3. Wen Liu
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Correspondence to Dandan Chen or Wen Liu.

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These authors contributed equally to this work.

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Lin, Z., Chen, D. & Liu, W. Biosynthesis-based artificial evolution of microbial natural products. Sci. China Chem. 59, 1175–1187 (2016). https://doi.org/10.1007/s11426-016-0062-x

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