In vivo biocombinatorial synthesis of lipopeptides by COM domain-mediated reprogramming of the surfactin biosynthetic complex

被引：54

作者：

Chiocchini, Claudia ^{[1
]}

Linne, Uwe ^{[1
]}

Stachelhaus, Torsten ^{[1
]}

机构：

[1] Univ Marburg, Fac Chem Biochem, D-35032 Marburg, Germany

来源：

CHEMISTRY & BIOLOGY | 2006年 / 13卷 / 08期

关键词：

D O I：

10.1016/j.chembiol.2006.06.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The intermolecular communication within NRPS complexes relies on the coordinated interplay of donor and acceptor communication-mediating (COM) domains. In this study, the potential of COM domains was exploited in vivo by establishing a system for the true biocombinatorial synthesis of lipopeptides via directed reprogramming of a natural NRP biosynthetic assembly line (i.e., surfactin). By means of COM domain swapping, these experiments verified the decisive role of COM domains for the control of protein-protein interactions between NRPSs, demonstrated the functionality of COM domain pairs even in the context of a heterologous host and NRPS system, and allowed for the intended skipping of a biosynthetic enzyme within a multienzymatic biosynthetic complex. Ultimately, abrogation of the selectivity barrier provided by COM domains afforded the successful simultaneous, biocombinatorial synthesis of distinct lipopeptide products.

引用

页码：899 / 908

页数：10

共 32 条

[1] Aminoacyl-CoAs as probes of condensation domain selectivity in nonribosomal peptide synthesis [J].

Belshaw, PJ ;

Walsh, CT ;

Stachelhaus, T .

SCIENCE, 1999, 284 (5413) :486-489

[2] The structure of docking domains in modular polyketide synthases [J].

Broadhurst, RW ;

Nietlispach, D ;

Wheatcroft, MP ;

Leadlay, PF ;

Weissman, KJ .

CHEMISTRY & BIOLOGY, 2003, 10 (08) :723-731

[3] Engineering of peptide synthetases - Key role of the thioesterase-like domain for efficient production of recombinant peptides [J].

deFerra, F ;

Rodriguez, F ;

Tortora, O ;

Tosi, C ;

Grandi, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (40) :25304-25309

[4] TRANSLATION OF THE OPEN READING FRAME ENCODED BY COMS, A GENE OF THE SRF OPERON, IS NECESSARY FOR THE DEVELOPMENT OF GENETIC COMPETENCE, BUT NOT SURFACTIN BIOSYNTHESIS, IN BACILLUS-SUBTILIS [J].

DSOUZA, C ;

NAKANO, MM ;

FRISBY, DL ;

ZUBER, P .

JOURNAL OF BACTERIOLOGY, 1995, 177 (14) :4144-4148

[5] IDENTIFICATION OF COMS, A GENE OF THE SRFA OPERON THAT REGULATES THE ESTABLISHMENT OF GENETIC COMPETENCE IN BACILLUS-SUBTILIS [J].

DSOUZA, C ;

NAKANO, MM ;

ZUBER, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (20) :9397-9401

[6] Exploitation of the selectivity-conferring code of nonribosomal peptide synthetases for the rational design of novel peptide antibiotics [J].

Eppelmann, K ;

Stachelhaus, T ;

Marahiel, MA .

BIOCHEMISTRY, 2002, 41 (30) :9718-9726

[7] Engineered biosynthesis of the peptide antibiotic bacitracin in the surrogate host Bacillus subtilis [J].

Eppelmann, K ;

Doekel, S ;

Marahiel, MA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (37) :34824-34831

[8] Role of linkers in communication between protein modules [J].

Gokhale, RS ;

Khosla, C .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2000, 4 (01) :22-27

[9] Antibiotic-resistance cassettes for Bacillus subtilis [J].

GueroutFleury, AM ;

Shazand, K ;

Frandsen, N ;

Stragier, P .

GENE, 1995, 167 (1-2) :335-336

[10] Selective interaction between nonribosomal peptide syntheltases is facilitated by short commuinication-mediating domains [J].

Hahn, M ;

Stachelhaus, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (44) :15585-15590

← 1 2 3 4 →