Heterogeneous Expression of the Biosynthetic Gene Clusters
Responsible for the Peptide Antibiotics in E.coli

GU Bin-Bin, HE Shan*, ZHU Peng, YAN Xiao-Jun

Chinese Journal of Biochemistry and Molecular Biology ›› 2013, Vol. 29 ›› Issue (2) : 128-138.

PDF(1355 KB)
PDF(1355 KB)
Chinese Journal of Biochemistry and Molecular Biology ›› 2013, Vol. 29 ›› Issue (2) : 128-138.
Reviews

Heterogeneous Expression of the Biosynthetic Gene Clusters
Responsible for the Peptide Antibiotics in E.coli

  • GU Bin-Bin, HE Shan, ZHU Peng, YAN Xiao-Jun
Author information +
History +

Abstract

Microorganisms produce a large number of secondary metabolites with amazing chemical diversities. Genome mining of their biosynthetic gene clusters and heterogeneous expression are essential for new drug discovery and yield improvement. In the past 20 years, numerous gene clusters responsible for the biosyntheses of important natural products have been identified. Among them, biosynthetic gene clusters for peptide antibiotics account for a large proportion. Peptide antibiotics have various biological activities including antibacterial, antitumor and antiviral activity,which have attracted considerable attention in chemical and pharmaceutical communities. Understanding of the biosynthetic mechanism and development of heterogeneous expression will pave the way for more rational structural modifications through combinant biosynthesis and yield improvements by metabolic engineering. E. coli, as the most extensive and successful expression system, is often employed to express exogenous genes. In general, E.coli is used to express one or several genes and rarely used to express the whole biosynthesis gene cluster. Since the first exogenous biosynthesis gene cluster responsible for polyketide 6deoxyerythronolide B (6dEB) was successfully expressed in E. coli in 2001(Khosla and Cane), E. coli as a heterogeneous host of gene cluster, has drawn high attention in the related fields. Then a number of ribosomal peptides and nonribosomal peptides gene clusters have been successively expressed in E. Coli. This review summarizes the advances in the heterogeneous expression of biosynthetic gene clusters for assembly of peptide antibiotics in E. coli.

Key words

ribosomal peptides(RPs) / nonribosomal peptides(NRPs) / biosynthetic gene clusters / heterogeneous expression

Cite this article

Download Citations
GU Bin-Bin, HE Shan*, ZHU Peng, YAN Xiao-Jun. Heterogeneous Expression of the Biosynthetic Gene Clusters
Responsible for the Peptide Antibiotics in E.coli[J]. Chinese Journal of Biochemistry and Molecular Biology, 2013, 29(2): 128-138

References

[ 1 ] Newman D J, Cragg G M, Snader K M. Natural Products as Sources of New Drugs over the Period 1981   
     −2002 [J] . J Nat Prod, 2003, 66 (7) : 1022–1037
[ 2 ] Walsh C T, Nolan E M. Morphing Peptide Backbones into Heterocycles [J] . Proc Natl Acad Sci U S A,
     2008, 105 (15) : 5655–5656
[ 3 ] Nolan E M, Walsh C T. How Nature Morphs Peptide Scaffolds into Antibiotics [J] . ChemBioChem,
     2009, 10 (1) : 34–53
[ 4 ]  Destoumieux-Garzón D, Peduzzi J, Rebuffat S. Focus on modified microcins: structural features and mechanisms of action [J] . Biochimie, 2002, 84 (5-6) : 511–519
[ 5 ]  Duquesne S, Destoumieux-Garzón D, Peduzzi J, et al. [J] . Nat Prod Rep, 2007, 24 (4) : 708–734Microcins, gene-encoded antibacterial peptides from enterobacteria
[ 6 ]  Duquesne S, Petit V, Peduzzi J, et al. Structural and functional diversity of microcins, gene-encoded antibacterial peptides from enterobacteria. [J] . J Mol Microbiol Biotechnol, 2007, 13 (4): 200–209
[ 7 ] Severinov K, Semenova E, Kazakov A, et al. Low-molecular-weight post-translationally modified microcins. [J] . Mol Microbiol, 2007, 65 (6): 1380–1394
[ 8 ] McAuliffe O, Ross R P, Hill C. Lantibiotics: structure, biosynthesis and mode of action.[J] . FEMS      Microbiol Rev, 2001, 25 (3) : 285–308
[ 9 ] Chatterjee C, Paul M, Xie L, et al.Biosynthesis and mode of action of lantibiotics[J] . Chem Rev,
     2005, 105 (2): 633–683
[10] Patton G C, van der Donk W A.New developments in lantibiotic biosynthesis and mode of action[J] .
     Curr Opin Microbiol, 2005, 8 (5): 543–551
[11] Schmidt E W, Nelson J T, Rasko D A, et al.Patellamide A and C biosynthesis by a microcin-like pathway in Prochloron didemni, the cyanobacterial symbiont of Lissoclinum patellaa [J] . Proc Natl        Acad Sci U S A, 2005, 102 (20) : 7315–7320
[12] Lee S W, Mitchell D A, Markley A L, et al. Discovery of a widely distributed toxin biosynthetic gene cluster[J] . Proc Natl Acad Sci U S A, 2008, 105 (15) : 5879–5884
[13]  Schwarzer D, Finking R, Marahiel M A. Nonribosomal peptides: from genes to products. [J] . Nat Prod Rep, 2003, 20 (3): 275–287
[14] Cane D E, Walsh C T, Khosla C. Harnessing the biosynthetic code: combinations, permutations, and mutations[J] .Science, (1998), 282 (5386) : 63–68 
[15]  Walsh C T. Polyketide and nonribosomal peptide antibiotics: modularity and versatility[J] .Science,
     2004, 303 (5665) : 1805–1810
[16] Kieser T, Bibb M J, Buttner M J, et al. Practical Streptomyces Genetics. Microbiology Today (Book
     Reviews), 2000
[17] Hutchinson C R. Polyketide and non-ribosomal peptide synthases: falling together by coming apart      [J] . Proc Natl Acad Sci U S A, 2003, 100 (6) : 3010–3012
[18] Desai R P, Leaf T, Woo E, et al. Enhanced production of heterologous macrolide aglycones by fed-batch cultivation of Streptomyces coelicolor [J] . J Ind Microbiol Biotechnol, 2002, 28 (5) : 297–301
[19] Thorpe H M, Smith M C. In Vitro Site-Specific Integration of Bacteriophage DNA Catalyzed by a      Recombinase of the Resolvase/Invertase Family [J] . Proc Natl Acad Sci U S A, 1998, 95 (10) :      5505–5510
[20] Pfeifer BA, Admiraal SJ, Gramajo H, et al. Biosynthesis of complex polyketides in a metabolically engineered strain of E. colii [J] .Science, 2001, 291 (5509) : 1790–1792
[21] Sivonen K, Börner T. Bioactive Compounds Produced by cyanobacteria. The Cyanobacteria: Molecular  
     biology, genomics and evolution (M).Caister Academic Press, Norfolk, United Kingdom. 2008, 7 : 159–197   
[22]  Magarvey N A, Beck Z Q, Golakoti T, et al. Biosynthetic characterization and chemoenzymatic assembly of the cryptophycins. Potent anticancer agents from cyanobionts [J] . ACS Chem
     Biol, 2006, 1 (12) : 766–779
[23]  Welker M, von Döhren H. Cyanobacterial peptides - nature's own combinatorial biosynthesis. [J] .
     FEMS Microbiol Rev, 2006, 30 (4) : 530–563
[24] Donia M S, Ravel J, Schmidt E W. A global assembly line for cyanobactins. [J] . Nat Chem Biol, 
     2008, 4 (6) : 341–343
[25]  Donia M S, Hathaway B J, Sudek S, et al. Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians[J] . Nat Chem Biol, 2006,2 (12) : 729–735
[26] Sudek S, Haygood M G, Youssef D T, et al. Structure of trichamide, a cyclic peptide from the bloom-forming cyanobacterium Trichodesmium erythraeum, predicted from the genome sequence     [J] . Appl Environ Microbiol, 2006, 72 (6) : 4382–4387
[27] Ziemert N, Ishida K, Quillardet P, et al. Microcyclamide biosynthesis in two strains of Microcystis aeruginosa: from structure to genes and vice versaa [J] . Appl Environ Microbiol, 2008, 74 (6) : 1791–     1797
[28] Salvatella X, Caba J M, Albericio F, et al. Solution structure of the antitumor candidate trunkamide A by 2D NMR and restrained simulated annealing methods. [J] . J Org Chem, 2003, 68 (2): 211–215
[29] Williams A B, Jacobs R S. A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line [J] .Cancer Lett, 71 (1-3) : 97–102
[30] Fu X, Do T, Schmitz F J, et al. New Cyclic Peptides from the Ascidian Lissoclinum patella[J] . J Nat
     Prod, 1998, 61 (12) : 1547–1551
[31]  Schnell N, Entian K D, Schneider U, et al. Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings.[J] . Nature, 1988, 333 (6170) : 276–278
[32] Van der Meer J R, Polman J, Beerthuyzen M M, et al. Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis[J] . J Bacteriol, 1993, 175 (9) : 2578–2588
[33] Balabas B E, Montgomery B L, Ong L E, et al. CotB is essential for complete activation of green light-induced genes during complementary chromatic adaptation in Fremyella diplosiphonis[J] . Mol      Microbiol, 2003, 50 (3) : 781–793
[34] González-Pastor J E, San Millán J L, Castilla M A, et al. Structure and organization of plasmid genes required to produce the translation inhibitor microcin C7[J] . J Bacteriol, 1995, 177 (24) : 7131–7140
[35] Fuller J D, Camus A C, Duncan C L, et al. Identification of a streptolysin S-associated gene cluster and its role in the pathogenesis of Streptococcus iniae disease[J] . Infect Immun, 2002, 70 (10) : 5730–     5739
[36] Breil B , Borneman J, Triplett E W.  A newly discovered gene, tfuA, involved in the production of the ribosomally synthesized peptide antibiotic trifolitoxin[J] . J Bacteriol, 1996, 178 (14) : 4150–4156
[37] Ichinose K, Bedford D J, Tornus D, et al. The granaticin biosynthetic gene cluster of Streptomyces violaceoruber Tü22: sequence analysis and expression in a heterologous host. [J]. Chem Biol, 1998, 5
     (11) : 647–659
[38]  Milne J C, Roy R S, Eliot A C, et al. Cofactor requirements and reconstitution of microcin B17 synthetase: a multienzyme complex that catalyzes the formation of oxazoles and thiazoles in the antibiotic microcin B17 [J] . Biochemistry, 1999, 38 (15) : 4768–4781
[39]  Gehring A M, Mori I I, Perry R D, et al. The nonribosomal peptide synthetase HMWP2 forms a thiazoline ring during biogenesis of yersiniabactin, an iron-chelating virulence factor of yersinia pestis [J] . Biochemistry, 1998, 37(48):17104
[40]  Banerjee S, Hansen J N. Structure and expression of a gene encoding the precursor of subtilin, a small protein antibiotic [J] . J Biol Chem. 1988, 263 (19): 9508-9514
[41]  Long P F, Dunlap W C, Battershill C N, et al. Shotgun cloning and heterologous expression of the patellamide gene cluster as a strategy to achieving sustained metabolite production [J] . Chembiochem, 2005, 6 (10) : 1760–1765
[42]  Béjà O, Suzuki M T, Koonin E V, et al. Construction and analysis of bacterial artificial chromosome libraries from a marine microbial assemblage[J] . Environ Microbiol, 2000, 2 (5) : 516–529
[43]  Sosio M, Giusino F, Cappellano C,et al. Artificial chromosomes for antibiotic-producing actinomycetes
[J] . Nat Biotechnol, 2000, 18 :343–345
[44]  Paerl H W, Fulton R S 3rd, Moisander P H, et al. Harmful freshwater algal blooms, with an emphasis on cyanobacteria [J] . Sci World J, 2001, 1 : 76–113
[45] Welker M, von Döhren H. Cyanobacterial peptides - nature's own combinatorial biosynthesis[J] .      FEMS Microbiol Rev, 2006, 30 (4) : 530–563
   [46]  Murakami M,et al. Microviridins, elastase inhibitors from the cyanobacterium Nostoc Sun Q, Ishida K, 
     minutum (NIES-26)[J] . Phytochemistry, 1997, 45 (6) : 1197–1202
[47] Okino T, Matsuda H, Murakami M, et al. New microviridins, elastase inhibitors from the blue-green
     Alga Microcystis aeruginosa [J] . Tetrahedron, 1995, 51 (39) : 10679–10686
[48]  Rohrlack T, Christoffersen K, Kaebernick M, et al. Cyanobacterial protease inhibitor microviridin J causes a lethal molting disruption in Daphnia pulicaria[J] .Appl Environ Microbiol, 2004, 70 (8) :
     5047–5050
[49] Fischbach M A, Walsh C T. Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms[J] . Chem Rev, 2006, 106 (8) : 3468–3496
[50]  Rouhiainen L, Paulin L, Suomalainen S, et al. Genes encoding synthetases of cyclic depsipeptides, anabaenopeptilides, in Anabaena strain 90[J] . Mol Microbiol, 2000, 37 (1) : 156–167
[51]  Ziemert N, Ishida K, Liaimer A, et al[J] . Angew Chem Int Ed Engl, 2008, 47 (40) : 7756–7759. Ribosomal synthesis of tricyclic depsipeptides in bloom-forming cyanobacteria
[52]  Leikoski N, Fewer D P, Sivonen K. Widespread occurrence and lateral transfer of the cyanobactin biosynthesis gene cluster in cyanobacteria [J] . Appl Environ Microbiol, 2009, 75 (3) : 853–857
[53] Leikoski N, Fewer D P, Jokela J, et al. Highly diverse cyanobactins in strains of the genus Anabaena     [J] . Appl Environ Microbiol, 2010, 76 (3) : 701–709
[54] Willey J M, van der Donk W A. Lantibiotics: peptides of diverse structure and function [J] . Annu Rev
      Microbiol, 2007, 61 : 477–501
[55] Rey M W, Ramaiya P, Nelson B A, et al. Complete genome sequence of the industrial bacterium Bacillus licheniformis and comparisons with closely related Bacillus species [J] . Genome Biol, 2004, 5 (10) : R77
[56] Begley M, Cotter P D, Hill C, et al. Identification of a novel two-peptide lantibiotic, lichenicidin, following rational genome mining for LanM proteins [J] . Appl Environ Microbiol, 2009, 75 (17) :      5451–5460
[57]  Dischinger J, Josten M, Szekat C, et al. Production of the novel two-peptide lantibiotic lichenicidin by Bacillus licheniformis DSM 13 [J] . PLoS One, 2009, 4 (8) : e6788
[58] Caetano T, Krawczyk J M, Mösker E, et al. Heterologous expression, biosynthesis, and mutagenesis of type II lantibiotics from Bacillus licheniformis in Escherichia coli[J] . Chem Biol, 2011, 18 (1) :
     90–100
[59] Lin Y, Teng K, Huan L, et al. Dissection of the bridging pattern of bovicin HJ50, a lantibiotic containing a characteristic disulfide bridgei[J] . Microbiol Res, 2011, 166 (3) : 146–154
[60] Steinerová N, Lipavská H, Stajner K, et al.Production of quinomycin A in Streptomyces lasaliensis. [J]
     .Folia Microbiol (Praha), 1987, 32 (1) : 1–5
[61] Watanabe K, Hotta K, Praseuth A P, et al. Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli[J] . Nat Chem Biol, 2006, 2 (8) : 423–428
[62] Watanabe K, Oikawa H Robust platform for de novo production of heterologous polyketides and nonribosomal peptides in Escherichia coli.[J] . Org Biomol Chem, 2007, 5 (4): 593–602
[63] Weissman K J, Leadlay P F. Combinatorial biosynthesis of reduced polyketides. [J] . Nat Rev Microbiol,
     2005, 3 (12) : 925–936
[64] Wenzel S C, Gross F, Zhang Y, et al. Heterologous expression of a myxobacterial natural productsassembly line in pseudomonads via red/ET recombineering [J] . Chem Biol, 2005, 12 (3) : 349–356
[65] Menzella H G, Reid R, Carney J R, et al. Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes [J] . Nat Biotechnol, 2005, 23 (9) :1171–1176

Funding

Supported by Zhejiang Marine Biotechnology Innovation Team(ZMBIT)(No. 2012R100292) ; Ningbo Marine Algae Biotechnology Team(NMABT)(No. 2011B81007) ; Qianjiang Talent Plan (No. 2012R10068); National Natural Science Foundation of China (No.40906080)

PDF(1355 KB)

635

Accesses

0

Citation

Detail

Sections
Recommended

/