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Engineering of E. coli for Heterologous Expression of Secondary Metabolite Biosynthesis Pathways Recovered from Metagenomics Libraries

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Functional Metagenomics: Tools and Applications

Abstract

A key component of the functional metagenomics approach for complex natural product discovery is the host system chosen to screen environmental DNA. The host must provide technical simplicity to enable high throughput assessment of the target compounds of interest. Furthermore, intracellular support is crucial to allowing biosynthesis of those compounds with the most chemical and bioactivity diversity. This chapter examines the characteristics of functional metagenomics screening hosts, including those historically used in discovery applications. An emphasis is placed on identifying desirable features of selected hosts and how engineering strategies may be applied to further enable the goals of compound discovery. A special emphasis is placed on the use of Streptomyces spp. and Escherichia coli as screening hosts and how the parallel field of heterologous biosynthesis engineering with these two hosts has interfaced with past and present objectives in functional metagenomics. Other screening hosts and future prospects for this component of metagenomics-based discovery are also discussed.

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References

  • Aakvik T, Degnes KF, Dahlsrud R, Schmidt F, Dam R, Yu L, Volker U, Ellingsen TE, Valla S (2009) A plasmid RK2-based broad-host-range cloning vector useful for transfer of metagenomic libraries to a variety of bacterial species. FEMS Microbiol Lett 296(2):149–158. doi:10.1111/j.1574-6968.2009.01639.x

    Article  CAS  PubMed  Google Scholar 

  • 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(6000):70–74. doi:10.1126/science.1191652. 330/6000/70 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Amann RI, Ludwig W, Schleifer KH (1995) Phylogenetic identification and in situ detection of individual microbial cells without cultivation. Microbiol Rev 59(1):143–169

    CAS  PubMed  PubMed Central  Google Scholar 

  • Andersson DI, Hughes D (2010) Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol 8(4):260–271. doi:10.1038/nrmicro2319. nrmicro2319 [pii]

    CAS  PubMed  Google Scholar 

  • Aneja P, Dai M, Lacorre DA, Pillon B, Charles TC (2004) Heterologous complementation of the exopolysaccharide synthesis and carbon utilization phenotypes of Sinorhizobium meliloti Rm1021 polyhydroxyalkanoate synthesis mutants. FEMS Microbiol Lett 239(2):277–283. doi:10.1016/j.femsle.2004.08.045

    Article  CAS  PubMed  Google Scholar 

  • August PR, Grossman TH, Minor C, Draper MP, MacNeil IA, Pemberton JM, Call KM, Holt D, Osburne MS (2000) Sequence analysis and functional characterization of the violacein biosynthetic pathway from Chromobacterium violaceum. J Mol Microbiol Biotechnol 2(4):513–519

    CAS  PubMed  Google Scholar 

  • Baker DD, Chu M, Oza U, Rajgarhia V (2007) The value of natural products to future pharmaceutical discovery. Nat Prod Rep 24(6):1225–1244. doi:10.1039/b602241n

    Article  CAS  PubMed  Google Scholar 

  • Baltz RH (2006) Marcel Faber Roundtable: is our antibiotic pipeline unproductive because of starvation, constipation or lack of inspiration? J Ind Microbiol Biotechnol 33(7):507–513. doi:10.1007/s10295-005-0077-9

    Article  CAS  PubMed  Google Scholar 

  • Barnes TA, Jinks A (2008) Methicillin-resistant Staphylococcus aureus: the modern-day challenge. Br J Nurs 17(16):1012, 1014, 1016–1018

    Google Scholar 

  • Bentley SD, Chater KF, Cerdeno-Tarraga AM, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang CH, Kieser T, Larke L, Murphy L, Oliver K, O’Neil S, Rabbinowitsch E, Rajandream MA, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, Barrell BG, Parkhill J, Hopwood DA (2002) Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 417(6885):141–147. doi:10.1038/417141a. 417141a [pii]

    Article  PubMed  Google Scholar 

  • Berdy J (2012) Thoughts and facts about antibiotics: where we are now and where we are heading. J Antibiot (Tokyo) 65(8):441. doi:10.1038/ja.2012.54

    Article  CAS  Google Scholar 

  • Bibb MJ, Freeman RF, Hopwood DA (1977) Physical and genetic characterization of a 2nd sex factor, Scp2, for streptomyces-coelicolor A3(2). Mol Gen Genet 154(2):155–166. doi:10.1007/Bf00330831

    Article  CAS  Google Scholar 

  • Bibb MJ, Ward JM, Hopwood DA (1978) Transformation of plasmid DNA into Streptomyces at high frequency. Nature 274(5669):398–400

    Article  CAS  PubMed  Google Scholar 

  • Blunt JW, Copp BR, Keyzers RA, Munro MH, Prinsep MR (2013) Marine natural products. Nat Prod Rep 30(2):237–323. doi:10.1039/c2np20112g

    Article  CAS  PubMed  Google Scholar 

  • Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, Bartlett J (2009) Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48(1):1–12. doi:10.1086/595011

    Article  PubMed  Google Scholar 

  • Brady SF, Clardy J (2000) Long-chain N-acyl amino acid antibiotics isolated from heterologously expressed environmental DNA. JACS 122:12903

    Article  CAS  Google Scholar 

  • Brady SF, Clardy J (2004) Palmitoylputrescine, an antibiotic isolated from the heterologous expression of DNA extracted from bromeliad tank water. J Nat Prod 67(8):1283–1286

    Article  CAS  PubMed  Google Scholar 

  • Brady SF, Clardy J (2005a) Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew Chem Int Ed Engl 44(43):7063–7065

    Article  CAS  PubMed  Google Scholar 

  • Brady SF, Clardy J (2005b) N-acyl derivatives of arginine and tryptophan isolated from environmental DNA expressed in Escherichia coli. Org Lett 7(17):3613–3616

    Article  CAS  PubMed  Google Scholar 

  • Brady SF, Chao CJ, Handelsman J, Clardy J (2001) Cloning and heterologous expression of a natural product biosynthetic gene cluster from eDNA. Org Lett 3(13):1981–1984

    Article  CAS  PubMed  Google Scholar 

  • Brady SF, Chao CJ, Clardy J (2002) New natural product families from an environmental DNA (eDNA) gene cluster. J Am Chem Soc 124(34):9968–9969

    Article  CAS  PubMed  Google Scholar 

  • Brady SF, Chao CJ, Clardy J (2004) Long-chain N-acyltyrosine synthases from environmental DNA. Appl Environ Microbiol 70(11):6865–6870. doi:10.1128/AEM.70.11.6865-6870.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carreras CW, Khosla C (1998) Purification and in vitro reconstitution of the essential protein components of an aromatic polyketide synthase. Biochemistry 37(8):2084–2088. doi:10.1021/bi972919+

    Article  CAS  PubMed  Google Scholar 

  • Carreras CW, Gehring AM, Walsh CT, Khosla C (1997) Utilization of enzymatically phosphopantetheinylated acyl carrier proteins and acetyl-acyl carrier proteins by the actinorhodin polyketide synthase. Biochemistry 36(39):11757–11761

    Article  CAS  PubMed  Google Scholar 

  • Cars O, Hedin A, Heddini A (2011) The global need for effective antibiotics-moving towards concerted action. Drug Resist Updat 14(2):68–69. doi:10.1016/j.drup.2011.02.006

    Article  PubMed  Google Scholar 

  • Chang FY, Brady SF (2013) Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening. Proc Natl Acad Sci U S A 110(7):2478–2483. doi:10.1073/pnas.1218073110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Courtois S, Cappellano CM, Ball M, Francou FX, Normand P, Helynck G, Martinez A, Kolvek SJ, Hopke J, Osburne MS, August PR, Nalin R, Guerineau M, Jeannin P, Simonet P, Pernodet JL (2003) Recombinant environmental libraries provide access to microbial diversity for drug discovery from natural products. Appl Environ Microbiol 69(1):49–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830(6):3670–3695. doi:10.1016/j.bbagen.2013.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craig JW, Chang FY, Brady SF (2009) Natural products from environmental DNA hosted in Ralstonia metallidurans. ACS Chem Biol 4(1):23–28. doi:10.1021/cb8002754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craig JW, Chang FY, Kim JH, Obiajulu SC, Brady SF (2010) Expanding small-molecule functional metagenomics through parallel screening of broad-host-range cosmid environmental DNA libraries in diverse proteobacteria. Appl Environ Microbiol 76(5):1633–1641. doi:10.1128/AEM.02169-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davies J (2011) How to discover new antibiotics: harvesting the parvome. Curr Opin Chem Biol 15(1):5–10. doi:10.1016/j.cbpa.2010.11.001

    Article  CAS  PubMed  Google Scholar 

  • Davies J, Ryan KS (2012) Introducing the parvome: bioactive compounds in the microbial world. ACS Chem Biol 7(2):252–259. doi:10.1021/cb200337h

    Article  CAS  PubMed  Google Scholar 

  • Demain AL (2009) Antibiotics: natural products essential to human health. Med Res Rev 29(6):821–842. doi:10.1002/med.20154

    Article  CAS  PubMed  Google Scholar 

  • Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot (Tokyo) 62(1):5–16. doi:10.1038/ja.2008.16

    Article  CAS  Google Scholar 

  • Dreier J, Shah AN, Khosla C (1999) Kinetic analysis of the actinorhodin aromatic polyketide synthase. J Biol Chem 274(35):25108–25112

    Article  CAS  PubMed  Google Scholar 

  • Embley TM (1996) Molecular Approaches to Environmental Microbiology. Prentice Hall, Essex

    Google Scholar 

  • Feitelson JS, Hopwood DA (1983) Cloning of a Streptomyces gene for an O-methyltransferase involved in antibiotic biosynthesis. Mol Gen Genet 190(3):394–398

    Article  CAS  PubMed  Google Scholar 

  • Fierer N, Bradford MA, Jackson RB (2007) Toward an ecological classification of soil bacteria. Ecology 88(6):1354–1364

    Article  PubMed  Google Scholar 

  • Fischbach MA, Walsh CT (2009) Antibiotics for emerging pathogens. Science 325(5944):1089–1093. doi:10.1126/science.1176667. 325/5944/1089 [pii]

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fox JL (2006) The business of developing antibacterials. Nat Biotechnol 24(12):1521–1528. doi:10.1038/nbt1206-1521

    Article  CAS  PubMed  Google Scholar 

  • Frense D (2007) Taxanes: perspectives for biotechnological production. Appl Microbiol Biotechnol 73(6):1233–1240

    Article  CAS  PubMed  Google Scholar 

  • Gabor EM, de Vries EJ, Janssen DB (2004) Construction, characterization, and use of small-insert gene banks of DNA isolated from soil and enrichment cultures for the recovery of novel amidases. Environ Microbiol 6(9):948–958. doi:10.1111/j.1462-2920.2004.00643.x

    Article  CAS  PubMed  Google Scholar 

  • George IF, Hartmann M, Liles MR, Agathos SN (2011) Recovery of as-yet-uncultured soil acidobacteria on dilute solid media. Appl Environ Microbiol 77(22):8184–8188. doi:10.1128/AEM.05956-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gillespie DE, Brady SF, Bettermann AD, Cianciotto NP, Liles MR, Rondon MR, Clardy J, Goodman RM, Handelsman J (2002) Isolation of antibiotics turbomycin a and B from a metagenomic library of soil microbial DNA. Appl Environ Microbiol 68(9):4301–4306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glauert AM, Hopwood DA (1959) A membranous component of the cytoplasm in Streptomyces coelicolor. J Biophys Biochem Cytol 6:515–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glauert AM, Hopwood DA (1960) The fine structure of Streptomyces coelicolor. I. The cytoplasmic membrane system. J Biophys Biochem Cytol 7:479–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glauert AM, Hopwood DA (1961) The fine structure of Streptomyces violaceoruber (S. coelicolor). III. The walls of the mycelium and spores. J Biophys Biochem Cytol 10:505–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gokhale RS, Hunziker D, Cane DE, Khosla C (1999a) Mechanism and specificity of the terminal thioesterase domain from the erythromycin polyketide synthase. Chem Biol 6(2):117–125

    Article  CAS  PubMed  Google Scholar 

  • Gokhale RS, Tsuji SY, Cane DE, Khosla C (1999b) Dissecting and exploiting intermodular communication in polyketide synthases. Science 284(5413):482–485

    Article  CAS  PubMed  Google Scholar 

  • Golomb M, Chamberlin M (1974) Characterization of T7-specific ribonucleic acid polymerase. IV. Resolution of the major in vitro transcripts by gel electrophoresis. J Biol Chem 249(9):2858–2863

    CAS  PubMed  Google Scholar 

  • Guan C, Ju J, Borlee BR, Williamson LL, Shen B, Raffa KF, Handelsman J (2007) Signal mimics derived from a metagenomic analysis of the gypsy moth gut microbiota. Appl Environ Microbiol 73(11):3669–3676. doi:10.1128/AEM.02617-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henne A, Daniel R, Schmitz RA, Gottschalk G (1999) Construction of environmental DNA libraries in Escherichia coli and screening for the presence of genes conferring utilization of 4-hydroxybutyrate. Appl Environ Microbiol 65(9):3901–3907

    CAS  PubMed  PubMed Central  Google Scholar 

  • Henne A, Schmitz RA, Bomeke M, Gottschalk G, Daniel R (2000) Screening of environmental DNA libraries for the presence of genes conferring lipolytic activity on Escherichia coli. Appl Environ Microbiol 66(7):3113–3116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopwood DA (1960) Phase-contrast observations on Streptomyces coelicolor. J Gen Microbiol 22:295–302

    Article  CAS  PubMed  Google Scholar 

  • Hopwood DA (1997) Genetic contributions to understanding polyketide synthases. Chem Rev 97(7):2465–2498

    Article  CAS  PubMed  Google Scholar 

  • Hopwood DA (1999) Forty years of genetics with Streptomyces: from in vivo through in vitro to in silico. Microbiology 145(Pt 9):2183–2202

    Article  CAS  PubMed  Google Scholar 

  • Hopwood DA (2003) Streptomyces genes: from Waksman to Sanger. J Ind Microbiol Biotechnol 30(8):468–471. doi:10.1007/s10295-003-0031-7

    Article  CAS  PubMed  Google Scholar 

  • Hopwood DA (2006) Soil to genomics: the Streptomyces chromosome. Annu Rev Genet 40:1–23. doi:10.1146/annurev.genet.40.110405.090639

    Article  CAS  PubMed  Google Scholar 

  • Hopwood DA, Glauert AM (1960) The fine structure of Streptomyces coelicolor. II. The nuclear material. J Biophys Biochem Cytol 8:267–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hopwood DA, Wright HM (1973) A plasmid of Streptomyces coelicolor carrying a chromosomal locus and its inter-specific transfer. J Gen Microbiol 79(2):331–342

    Article  CAS  PubMed  Google Scholar 

  • Jennewein S, Croteau R (2001) Taxol: biosynthesis, molecular genetics, and biotechnological applications. Appl Microbiol Biotechnol 57(1–2):13–19

    CAS  PubMed  Google Scholar 

  • Kakirde KS, Wild J, Godiska R, Mead DA, Wiggins AG, Goodman RM, Szybalski W, Liles MR (2011) Gram negative shuttle BAC vector for heterologous expression of metagenomic libraries. Gene 475(2):57–62. doi:10.1016/j.gene.2010.11.004

    Article  CAS  PubMed  Google Scholar 

  • Kao CM, Katz L, Khosla C (1994) Engineered biosynthesis of a complete macrolactone in a heterologous host. Science 265(5171):509–512

    Article  CAS  PubMed  Google Scholar 

  • Kardos N, Demain AL (2011) Penicillin: the medicine with the greatest impact on therapeutic outcomes. Appl Microbiol Biotechnol 92(4):677–687. doi:10.1007/s00253-011-3587-6

    Article  CAS  PubMed  Google Scholar 

  • Katz ML, Mueller LV, Polyakov M, Weinstock SF (2006) Where have all the antibiotic patents gone? Nat Biotechnol 24(12):1529–1531. doi:10.1038/nbt1206-1529

    Article  CAS  PubMed  Google Scholar 

  • Kellner H, Luis P, Portetelle D, Vandenbol M (2011) Screening of a soil metatranscriptomic library by functional complementation of Saccharomyces cerevisiae mutants. Microbiol Res 166(5):360–368. doi:10.1016/j.micres.2010.07.006

    Article  CAS  PubMed  Google Scholar 

  • Kieser T, Hopwood DA, Wright HM, Thompson CJ (1982) pIJ101, a multi-copy broad host-range Streptomyces plasmid: functional analysis and development of DNA cloning vectors. Mol Gen Genet 185(2):223–228

    Article  CAS  PubMed  Google Scholar 

  • Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA (2000) Practical Streptomyces genetics. The John Innes Foundation, Norwich

    Google Scholar 

  • Kingston DG (1994) Taxol: the chemistry and structure-activity relationships of a novel anticancer agent. Trends Biotechnol 12(6):222–227

    Article  CAS  PubMed  Google Scholar 

  • Kirby R, Wright LF, Hopwood DA (1975) Plasmid-determined antibiotic synthesis and resistance in Streptomyces coelicolor. Nature 254(5497):265–267

    Article  CAS  PubMed  Google Scholar 

  • Knietsch A, Waschkowitz T, Bowien S, Henne A, Daniel R (2003) Metagenomes of complex microbial consortia derived from different soils as sources for novel genes conferring formation of carbonyls from short-chain polyols on Escherichia coli. J Mol Microbiol Biotechnol 5 (1):46–56. doi:68724

    Google Scholar 

  • Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4(3):206–220

    Article  CAS  PubMed  Google Scholar 

  • Lambalot RH, Gehring AM, Flugel RS, Zuber P, LaCelle M, Marahiel MA, Reid R, Khosla C, Walsh CT (1996) A new enzyme superfamily—the phosphopantetheinyl transferases. Chem Biol 3(11):923–936

    Article  CAS  PubMed  Google Scholar 

  • Lederberg J (2000) Infectious history. Science 288(5464):287–293

    Article  CAS  PubMed  Google Scholar 

  • Lee SY (1996) High cell-density culture of Escherichia coli. Trends Biotechnol 14(3):98–105. doi:10.1016/0167-7799(96)80930-9. 0167-7799(96)80930-9 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Lee HY, Khosla C (2007) Bioassay-guided evolution of glycosylated macrolide antibiotics in Escherichia coli. PLoS Biol 5(2):e45

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li JW, Vederas JC (2009) Drug discovery and natural products: end of an era or an endless frontier? Science 325(5937):161–165. doi:10.1126/science.1168243

    Article  PubMed  CAS  Google Scholar 

  • Lim HK, Chung EJ, Kim JC, Choi GJ, Jang KS, Chung YR, Cho KY, Lee SW (2005) Characterization of a forest soil metagenome clone that confers indirubin and indigo production on Escherichia coli. Appl Environ Microbiol 71(12):7768–7777. doi:10.1128/AEM.71.12.7768-7777.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lydiate DJ, Malpartida F, Hopwood DA (1985) The Streptomyces plasmid SCP2*: its functional analysis and development into useful cloning vectors. Gene 35(3):223–235

    Article  CAS  PubMed  Google Scholar 

  • MacNeil IA, Tiong CL, Minor C, August PR, Grossman TH, Loiacono KA, Lynch BA, Phillips T, Narula S, Sundaramoorthi R, Tyler A, Aldredge T, Long H, Gilman M, Holt D, Osburne MS (2001) Expression and isolation of antimicrobial small molecules from soil DNA libraries. J Mol Microbiol Biotechnol 3(2):301–308

    CAS  PubMed  Google Scholar 

  • Majernik A, Gottschalk G, Daniel R (2001) Screening of environmental DNA libraries for the presence of genes conferring Na(+)(Li(+))/H(+) antiporter activity on Escherichia coli: characterization of the recovered genes and the corresponding gene products. J Bacteriol 183(22):6645–6653. doi:10.1128/JB.183.22.6645-6653.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malpartida F, Hopwood DA (1984) Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host. Nature 309(5967):462–464

    Article  CAS  PubMed  Google Scholar 

  • Martinez A, Kolvek SJ, Yip CL, Hopke J, Brown KA, MacNeil IA, Osburne MS (2004) Genetically modified bacterial strains and novel bacterial artificial chromosome shuttle vectors for constructing environmental libraries and detecting heterologous natural products in multiple expression hosts. Appl Environ Microbiol 70(4):2452–2463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McAllister WT, Morris C, Rosenberg AH, Studier FW (1981) Utilization of bacteriophage T7 late promoters in recombinant plasmids during infection. J Mol Biol 153(3):527–544

    Article  CAS  PubMed  Google Scholar 

  • Molinari G (2009) Natural products in drug discovery: present status and perspectives. Adv Exp Med Biol 655:13–27. doi:10.1007/978-1-4419-1132-2_2

    Article  CAS  PubMed  Google Scholar 

  • Mutka SC, Carney JR, Liu Y, Kennedy J (2006) Heterologous production of epothilone C and D in Escherichia coli. Biochemistry 45(4):1321–1330

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75(3):311–335. doi:10.1021/np200906s

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newman DJ, Cragg GM, Battershill CN (2009) Therapeutic agents from the sea: biodiversity, chemo-evolutionary insight and advances to the end of Darwin’s 200th year. Diving Hyperb Med 39(4):216–225

    PubMed  Google Scholar 

  • Nicolaou KC, Montagnon T (2008) Molecules that changed the world. Wiley, Weinheim

    Google Scholar 

  • Ongley SE, Bian X, Neilan BA, Muller R (2013) Recent advances in the heterologous expression of microbial natural product biosynthetic pathways. Nat Prod Rep 30(8):1121–1138. doi:10.1039/c3np70034h

    Article  CAS  PubMed  Google Scholar 

  • Pace NR, Stahl DA, Lane DJ, Olsen GJ (1986) The analysis of natural microbial-populations by ribosomal-RNA sequences. Adv Microb Ecol 9:1–55

    Article  CAS  Google Scholar 

  • Peiru S, Menzella HG, Rodriguez E, Carney J, Gramajo H (2005) Production of the potent antibacterial polyketide erythromycin C in Escherichia coli. Appl Environ Microbiol 71(5):2539–2547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pelaez F (2006) The historical delivery of antibiotics from microbial natural products—can history repeat? Biochem Pharmacol 71(7):981–990. doi:10.1016/j.bcp.2005.10.010

    Article  CAS  PubMed  Google Scholar 

  • Pfeifer BA, Khosla C (2001) Biosynthesis of polyketides in heterologous hosts. Microbiol Mol Biol Rev 65(1):106–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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(5509):1790–1792

    Article  CAS  PubMed  Google Scholar 

  • Pfeifer BA, Wang CC, Walsh CT, Khosla C (2003) Biosynthesis of Yersiniabactin, a complex polyketide-nonribosomal peptide, using Escherichia coli as a heterologous host. Appl Environ Microbiol 69(11):6698–6702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quadri LE, Weinreb PH, Lei M, Nakano MM, Zuber P, Walsh CT (1998) Characterization of Sfp, a Bacillus subtilis phosphopantetheinyl transferase for peptidyl carrier protein domains in peptide synthetases. Biochemistry 37(6):1585–1595

    Article  CAS  PubMed  Google Scholar 

  • Rahman H, Austin B, Mitchell WJ, Morris PC, Jamieson DJ, Adams DR, Spragg AM, Schweizer M (2010) Novel anti-infective compounds from marine bacteria. Mar Drugs 8(3):498–518. doi:10.3390/md8030498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rappe MS, Giovannoni SJ (2003) The uncultured microbial majority. Annu Rev Microbiol 57:369–394. doi:10.1146/annurev.micro.57.030502.090759

    Article  CAS  PubMed  Google Scholar 

  • Roberts GA, Staunton J, Leadlay PF (1993) Heterologous expression in Escherichia coli of an intact multienzyme component of the erythromycin-producing polyketide synthase. Eur J Biochem 214(1):305–311

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez E, Gramajo H (1999) Genetic and biochemical characterization of the alpha and beta components of a propionyl-CoA carboxylase complex of Streptomyces coelicolor A3(2). Microbiology 145(Pt 11):3109–3119

    Article  CAS  PubMed  Google Scholar 

  • Roemer T, Xu D, Singh SB, Parish CA, Harris G, Wang H, Davies JE, Bills GF (2011) Confronting the challenges of natural product-based antifungal discovery. Chem Biol 18(2):148–164. doi:10.1016/j.chembiol.2011.01.009

    Article  CAS  PubMed  Google Scholar 

  • Rondon MR, August PR, Bettermann AD, Brady SF, Grossman TH, Liles MR, Loiacono KA, Lynch BA, MacNeil IA, Minor C, Tiong CL, Gilman M, Osburne MS, Clardy J, Handelsman J, Goodman RM (2000) Cloning the soil metagenome: a strategy for accessing the genetic and functional diversity of uncultured microorganisms. Appl Environ Microbiol 66(6):2541–2547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schipper C, Hornung C, Bijtenhoorn P, Quitschau M, Grond S, Streit WR (2009) Metagenome-derived clones encoding two novel lactonase family proteins involved in biofilm inhibition in Pseudomonas aeruginosa. Appl Environ Microbiol 75(1):224–233. doi:10.1128/AEM.01389-08

    Article  CAS  PubMed  Google Scholar 

  • Schrempf H, Bujard H, Hopwood DA, Goebel W (1975) Isolation of covalently closed circular deoxyribonucleic acid from Streptomyces coelicolor A3(2). J Bacteriol 121(2):416–421

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shiloach J, Fass R (2005) Growing E. coli to high cell density—a historical perspective on method development. Biotechnol Adv 23(5):345–357. doi:10.1016/j.biotechadv.2005.04.004. S0734-9750(05)00046-7 [pii]

    Article  CAS  PubMed  Google Scholar 

  • Song MC, Kim EJ, Kim E, Rathwell K, Nam SJ, Yoon YJ (2014) Microbial biosynthesis of medicinally important plant secondary metabolites. Nat Prod Rep 31(11):1497–1509. doi:10.1039/c4np00057a

    Article  CAS  PubMed  Google Scholar 

  • Spizek J, Novotna J, Rezanka T, Demain AL (2010) Do we need new antibiotics? The search for new targets and new compounds. J Ind Microbiol Biotechnol 37(12):1241–1248. doi:10.1007/s10295-010-0849-8

    Article  CAS  PubMed  Google Scholar 

  • Studier FW, Moffatt BA (1986) Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J Mol Biol 189(1):113–130

    Article  CAS  PubMed  Google Scholar 

  • Swartz JR (1996) Escherichia coli recombinant DNA technology. In: Neidhardt FC (ed) Escherichia coli and Salmonella typhimurium, vol 2, 2nd edn. American Society for Microbiology, Washington, DC, pp 1693–1711

    Google Scholar 

  • Torsvik V, Goksoyr J, Daae FL (1990) High diversity in DNA of soil bacteria. Appl Environ Microbiol 56(3):782–787

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vederas JC (2014) Explorations of fungal biosynthesis of reduced polyketides—a personal viewpoint. Nat Prod Rep 31(10):1253–1259. doi:10.1039/c4np00091a

    Article  CAS  PubMed  Google Scholar 

  • Verdine GL (1996) The combinatorial chemistry of nature. Nature 384(6604 Suppl):11–13. doi:10.1038/384011a0

    CAS  PubMed  Google Scholar 

  • Wang Y, Pfeifer BA (2008) 6-Deoxyerythronolide B production through chromosomal localization of the deoxyerythronolide B synthase genes in E. coli. Metab Eng 10(1):33–38

    Article  PubMed  CAS  Google Scholar 

  • Wang GY, Graziani E, Waters B, Pan W, Li X, McDermott J, Meurer G, Saxena G, Andersen RJ, Davies J (2000) Novel natural products from soil DNA libraries in a streptomycete host. Org Lett 2(16):2401–2404

    Article  CAS  PubMed  Google Scholar 

  • Watanabe K, Hotta K, Praseuth AP, Koketsu K, Migita A, Boddy CN, Wang CC, Oguri H, Oikawa H (2006) Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. Nat Chem Biol 2(8):423–428

    Article  CAS  PubMed  Google Scholar 

  • Wenzel SC, Gross F, Zhang Y, Fu J, Stewart AF, Muller R (2005) Heterologous expression of a myxobacterial natural products assembly line in pseudomonads via red/ET recombineering. Chem Biol 12(3):349–356

    Article  CAS  PubMed  Google Scholar 

  • Wild J, Szybalski W (2004) Copy-control pBAC/oriV vectors for genomic cloning. Methods Mol Biol 267:145–154. doi:10.1385/1-59259-774-2:145

    CAS  PubMed  Google Scholar 

  • Wild J, Hradecna Z, Posfai G, Szybalski W (1996) A broad-host-range in vivo pop-out and amplification system for generating large quantities of 50- to 100-kb genomic fragments for direct DNA sequencing. Gene 179(1):181–188

    Article  CAS  PubMed  Google Scholar 

  • Wild J, Hradecna Z, Szybalski W (2001) Single-copy/high-copy (SC/HC) pBAC/oriV novel vectors for genomics and gene expression. Plasmid 45:142

    Google Scholar 

  • Wild J, Hradecna Z, Szybalski W (2002) Conditionally amplifiable BACs: switching from single-copy to high-copy vectors and genomic clones. Genome Res 12(9):1434–1444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yun J, Kang S, Park S, Yoon H, Kim MJ, Heu S, Ryu S (2004) Characterization of a novel amylolytic enzyme encoded by a gene from a soil-derived metagenomic library. Appl Environ Microbiol 70(12):7229–7235. doi:10.1128/AEM.70.12.7229-7235.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Wang Y, Pfeifer BA (2008) Bacterial hosts for natural product production. Mol Pharm 5(2):212–225

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Wang Y, Boghigian B, Pfeifer BA (2009) Probing the heterologous metabolism supporting 6-deoxyerythronolide B biosynthesis in E. coli. Microb Biotechnol 2(3):390–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Boghigian BA, Pfeifer BA (2010a) Investigating the role of native propionyl-CoA and methylmalonyl-CoA metabolism on heterologous polyketide production in Escherichia coli. Biotechnol Bioeng 105(3):567–573. doi:10.1002/bit.22560

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Wang Y, Wu J, Skalina K, Pfeifer BA (2010b) Complete biosynthesis of erythromycin A and designed analogs using E. coli as a heterologous host. Chem Biol 17(11):1232–1240. doi:10.1016/j.chembiol.2010.09.013

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Boghigian BA, Armando J, Pfeifer BA (2011) Methods and options for the heterologous production of complex natural products. Nat Prod Rep 28(1):125–151. doi:10.1039/c0np00037j

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY, 14260-4200, USA

    Lei Fang, Guojian Zhang & Blaine A. Pfeifer

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  1. Lei Fang
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  2. Guojian Zhang
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  3. Blaine A. Pfeifer
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Correspondence to Blaine A. Pfeifer .

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  1. Department of Biology, University of Waterloo , Waterloo, Ontario, Canada

    Trevor C. Charles

  2. Department of Biological Sciences, Auburn University , Auburn, Alabama, USA

    Mark R. Liles

  3. Biorescources, AIT Austrian Institute of Technology Biorescources, Tulln, Austria

    Angela Sessitsch

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Fang, L., Zhang, G., Pfeifer, B.A. (2017). Engineering of E. coli for Heterologous Expression of Secondary Metabolite Biosynthesis Pathways Recovered from Metagenomics Libraries. In: Charles, T., Liles, M., Sessitsch, A. (eds) Functional Metagenomics: Tools and Applications. Springer, Cham. https://doi.org/10.1007/978-3-319-61510-3_3

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