Synthesis 2014; 46(16): 2122-2132
DOI: 10.1055/s-0034-1378359
short review
© Georg Thieme Verlag Stuttgart · New York

Access to High Value Natural and Unnatural Products through Hyphenating Chemical Synthesis and Biosynthesis

Kevin P. P. Mahoney
School of Chemistry and BSRC, University of St Andrews, St Andrews, KY16 9ST, UK   Fax: +44(1334)463808   Email: rjmg@st-andrews.ac.uk
,
Duncan R. M. Smith
School of Chemistry and BSRC, University of St Andrews, St Andrews, KY16 9ST, UK   Fax: +44(1334)463808   Email: rjmg@st-andrews.ac.uk
,
Emma J. A. Bogosyan
School of Chemistry and BSRC, University of St Andrews, St Andrews, KY16 9ST, UK   Fax: +44(1334)463808   Email: rjmg@st-andrews.ac.uk
,
Rebecca J. M. Goss*
School of Chemistry and BSRC, University of St Andrews, St Andrews, KY16 9ST, UK   Fax: +44(1334)463808   Email: rjmg@st-andrews.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 08 April 2014

Accepted after revision: 04 June 2014

Publication Date:
09 July 2014 (online)


Abstract

Access to natural products and their analogues is crucial. Such compounds have, for many years, played a central role in the area of drug discovery as well as in providing tools for chemical biology­. The ability to quickly and inexpensively acquire genome sequences has accelerated the field of natural product research. Access to genomic data coupled with new technologies for the engineering of organisms is resulting in the identification of large numbers of previously undiscovered natural products as well as an increased understanding of how the biosynthetic pathways responsible for the biogenesis of these compounds may be manipulated. This short review summarizes and reflects upon approaches to accessing natural products and has a particular focus on approaches combining molecular biology and synthetic chemistry.

1 Introduction

2 CHEM: Total Synthesis

3 BIO-CHEM: Semi-Synthesis

4 CHEM-BIO: Precursor Directed Biosynthesis

5 BIO-CHEM-BIO: Mutasynthesis

6 BIO-BIO: Combinatorial Biosynthesis

7 BIO-BIO-CHEM: Genochemetics: Gene Expression Enabling Synthetic Diversification

8 Conclusions and Future Directions in Natural Product Analogue Generation

 
  • References

  • 1 Cragg GM, Newman DJ, Snader KM. J. Nat. Prod. 1997; 60: 52
  • 2 Rouhi AM. Chem. Eng. News 2003; 81 (41): 77
  • 3 Kirschning A, Hahn F. Angew. Chem. Int. Ed. 2012; 51: 4012
  • 4 Goss RJ. M, Shankar S, Fayad AA. Nat. Prod. Rep. 2012; 29: 870
    • 5a Nicolaou KC, Sorensen EJ. Classics in Total Synthesis: Targets, Strategies, Methods . Wiley; New York: 1996
    • 5b Nicolaou KC, Snyder S. Classics in Total Synthesis II: More Targets, Strategies, Methods. Vol. 2. Wiley; New York: 2003
    • 5c Nicolaou KC, Chen JS. Classics in Total Synthesis III. Wiley; New York: 2011
  • 6 Vinothkumar S, Parameswaran PS. Biotechnol. Adv. 2013; 31: 1826
  • 7 Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsky BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA. Cancer Res. 2001; 61: 1013
  • 8 Yu MJ, Zheng W, Seletsky BM. Nat. Prod. Rep. 2013; 30: 1158
  • 9 Elford TG, Nave S, Sonawane RP, Aggarwal VK. J. Am. Chem. Soc. 2011; 133: 16798
  • 10 Nuhant P, Roush WR. J. Am. Chem. Soc. 2013; 135: 5340
  • 11 Hu DX, Clift MD, Lazarski KE, Thomson RJ. J. Am. Chem. Soc. 2011; 133: 1799
  • 12 Takada A, Hashimoto Y, Takikawa H, Hikita K, Suzuki K. Angew. Chem. Int. Ed. 2011; 50: 2297
  • 13 Custar DW, Zabawa TP, Hines J, Crews CM, Scheidt KA. J. Am. Chem. Soc. 2009; 131: 12406
  • 14 Florence GJ, Morris JC, Murray RG, Osler JD, Reddy VR, Smith TK. Org. Lett. 2011; 13: 514
  • 15 Smith TE, Fink SJ, Levine ZG, McClelland KA, Zackheim AA, Daub ME. Org. Lett. 2012; 14: 1452
  • 16 Nicolaou KC, Seo JH, Nakamura T, Aversa RJ. J. Am. Chem. Soc. 2011; 133: 214
  • 17 Evans PA, Huang M, Lawler MJ, Maroto S. Nat. Chem. 2012; 4: 680
  • 18 Sheehan JC. Ann. N. Y. Acad. Sci. 1967; 145: 216
  • 19 Kardos N, Demain AL. Appl. Microbiol. Biotechnol. 2011; 92: 677
  • 20 Courvalin P. Clin. Infect. Dis. 2006; 42: S25
  • 21 Nakama Y, Yoshida O, Yoda M, Araki K, Sawada Y, Nakamura J, Xu S, Miura K, Maki H, Arimoto H. J. Med. Chem. 2010; 53: 2528
  • 22 Xie J, Pierce JG, James RC, Okano A, Boger DL. J. Am. Chem. Soc. 2011; 133: 13946
  • 23 Pinchman JR, Boger DL. J. Med. Chem. 2013; 56: 4116
  • 24 Pathak TP, Miller SJ. J. Am. Chem. Soc. 2012; 134: 6120
  • 25 Pathak TP, Miller SJ. J. Am. Chem. Soc. 2013; 135: 8415
  • 26 Barrett KT, Miller SJ. J. Am. Chem. Soc. 2013; 135: 2963
  • 27 Lichtor PA, Miller SJ. Nat. Chem. 2012; 4: 990
  • 28 Cuevas C, Pérez M, Martín MJ, Chicharro JL, Fernández-Rivas C, Flores M, Francesch P, Gallego M, Zarzuelo F, de la Calle J, García C, Polanco I, Rodríguez I, Manzanares A. Org. Lett. 2000; 2: 2545
  • 29 Kawagishi F, Toma T, Inui T, Yokoshima Fukuyama T. J. Am. Chem. Soc. 2013; 135: 13684
  • 30 Chen J, Chen X, Bois-Choussy ZhuJ. J. Am. Chem. Soc. 2006; 128: 87
  • 31 Clark BR, O’Connor SE, Fox D, Leroy J, Murphy CD. Org. Biomol. Chem. 2011; 9: 6306
  • 32 Clark BR, Murphy CD. Org. Biomol. Chem. 2009; 7: 111
  • 33 Pan E, Oswald NW, Legako AG, Life JM, Posner BA, MacMillan JB. Chem. Sci. 2013; 4: 482
  • 34 Grüschow S, Rackham EJ, Elkins B, Newill PL. A, Hill LM, Goss RJ. M. ChemBioChem 2009; 10: 355
  • 35 Ragab AE, Grüschow S, Rackham EJ, Goss RJ. M. Org. Biomol. Chem. 2010; 8: 3128
  • 36 Glenn WS, Nims E, O’Connor SE. J. Am. Chem. Soc. 2011; 133: 19346
  • 37 Lussier F, Colatriano D, Wiltshire Z, Page JE, Martin VJ. J. Comput. Struct. Biotechnol. J. 2012; 3: e201210020
  • 38 Lee HY, Harvey CJ. B, Cane DE, Khosla C. J. Antibiot. 2011; 64: 59
  • 39 Goss RJ. M, Lanceron S, Deb Roy A, Sprague S, Nure-Alam M, Hughes DL, Wilkinson B, Moss SJ. ChemBioChem 2010; 11: 698
  • 40 Kim DH, Ryu JH, Lee KS, Lee BM, Lee MO, Lim S, Maeng PJ. Appl. Microbiol. Biotechnol. 2013; 97: 5881
  • 41 Amir-Heidari B, Thirlway J, Micklefield J. Org. Biomol. Chem. 2008; 6: 975
  • 42 Eichner S, Floss HG, Sasse F, Kirschning A. ChemBioChem 2009; 10: 1801
  • 43 Kim W, Lee JS, Lee D, Cai XF, Shin JC, Lee K, Lee C, Ryu S, Paik S, Lee JJ, Hong Y. ChemBioChem 2007; 8: 1491
  • 44 Runguphan W, Maresh JJ, O’Connor SE. Proc. Natl. Acad. Sci. U.S.A. 2009; 106: 13673
  • 45 Runguphan W, O’Connor SE. Org. Lett. 2013; 15: 2850
  • 46 Squire CM, Goss RJ. M, Hong H, Leadlay PF, Staunton J. ChemBioChem 2003; 4: 1225
  • 47 Mo S, Kim BS, Reynolds KA. Chem. Biol. 2005; 12: 191
  • 48 Murphy AC, Fukuda D, Song Z, Hothersall J, Cox RJ, Willis CL, Thomas CM, Simpson TJ. Angew. Chem. Int. Ed. 2011; 50: 3271
  • 49 Thomas I, Martin CJ, Wilkinson CJ, Staunton J, Leadlay PF. Chem. Biol. 2002; 9: 781
  • 50 Wu N, Cane DE, Khosla C. Biochemistry 2002; 41: 5056
  • 51 Wu N, Kudo F, Cane DE, Khosla C. J. Am. Chem. Soc. 2000; 122: 4847
  • 52 Kao CM, McPherson M, McDaniel RN, Fu H, Cane DE, Khosla C. J. Am. Chem. Soc. 1997; 119: 11339
  • 53 Caffrey P. Chem. Biol. 2005; 12: 1060
  • 54 Shepherd MD, Liu T, Mendez C, Salas JA, Rohr J. Appl. Environ. Microbiol. 2011; 77: 435
  • 55 Pérez M, Baig I, Braña AF, Salas JA, Rohr J, Méndez C. ChemBioChem 2008; 9: 2295
  • 56 Heide L, Westrich L, Anderle C, Gust B, Kammerer B, Piel J. ChemBioChem 2008; 9: 1992
  • 57 O’Connor SE. Meth. Enzymol. 2012; 515: 189
  • 58 Roy AD, Grüschow S, Cairns N, Goss RJ. M. J. Am. Chem. Soc. 2010; 132: 12243
  • 59 Walker MC, Thuronyi BW, Charkoudian LK, Lowry B, Khosla C, Chang MC. Y. Science 2013; 341: 1089
  • 60 Omura S, Ikeda H, Malpartida F, Kieser HM, Hopwood DA. Antimicrob. Agents Chemother. 1986; 29: 13
  • 61 Nguyen KT, Ritz D, Gu JQ, Alexander D, Chu M, Miao V, Brian P, Baltz RH. Proc. Natl. Acad. Sci. U.S.A. 2006; 103: 17462
  • 62 Roy AD, Grüschow S, Cairns N, Goss RJ. M. J. Am. Chem. Soc. 2010; 132: 12243
  • 63 Smith DR, Grüschow S, Goss RJ. Curr. Opin. Chem. Biol. 2013; 17: 276
  • 64 Dong C, Flecks S, Unversucht S, Haupt C, van Pee KH, Naismith JH. Science 2005; 309: 2216
  • 65 Barder TE, Walker SD, Martinelli JR, Buchwald SL. J. Am. Chem. Soc. 2005; 127: 4685
  • 66 Osbourn A, Goss RJ. M, Carter GT. Natural Products: Discourse, Diversity, and Design . Wiley; New York: 2014