Functional dissection and module swapping of fungal cyclooligomer depsipeptide synthetases.

BbBSLS and BbBEAS were dissected and reconstituted in Saccharomyces cerevisiae. The intermodular linker is essential for the reconstitution of the separate modules. Module 1 can be swapped between BbBEAS and BbBSLS, while modules 2 and 3 control the product profiles. BbBSLS is a flexible enzyme that also synthesizes beauvericins.

[1]  I. Molnár,et al.  Biosynthesis of the cyclooligomer depsipeptide beauvericin, a virulence factor of the entomopathogenic fungus Beauveria bassiana. , 2008, Chemistry & biology.

[2]  Gitanjali Yadav,et al.  NRPS-PKS: a knowledge-based resource for analysis of NRPS/PKS megasynthases , 2004, Nucleic Acids Res..

[3]  M. Marahiel,et al.  Construction of hybrid peptide synthetases by module and domain fusions. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Vederas,et al.  Complete Reconstitution of a Highly Reducing Iterative Polyketide Synthase , 2009, Science.

[5]  I. Molnár,et al.  Cytotoxic and Antihaptotactic beauvericin analogues from precursor-directed biosynthesis with the insect pathogen Beauveria bassiana ATCC 7159. , 2007, Journal of natural products.

[6]  S. Cheevadhanarak,et al.  Identification of the nonribosomal peptide synthetase gene responsible for bassianolide synthesis in wood-decaying fungus Xylaria sp. BCC1067. , 2008, Microbiology.

[7]  David R. Liu,et al.  Directed evolution can rapidly improve the activity of chimeric assembly-line enzymes , 2007, Proceedings of the National Academy of Sciences.

[8]  I. Molnár,et al.  Biosynthesis of the cyclooligomer depsipeptide bassianolide, an insecticidal virulence factor of Beauveria bassiana. , 2009, Fungal genetics and biology : FG & B.

[9]  T. Stachelhaus,et al.  Harnessing the potential of communication-mediating domains for the biocombinatorial synthesis of nonribosomal peptides. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Pieper,et al.  Bacterial expression of catalytically active fragments of the multifunctional enzyme enniatin synthetase. , 1994, Journal of molecular biology.

[11]  I. Molnár,et al.  Fungal cyclooligomer depsipeptides: from classical biochemistry to combinatorial biosynthesis. , 2011, Natural product reports.

[12]  Jixun Zhan,et al.  Search for cell motility and angiogenesis inhibitors with potential anticancer activity: beauvericin and other constituents of two endophytic strains of Fusarium oxysporum. , 2007, Journal of natural products.

[13]  A. Logrieco,et al.  Beauvericin Production by FusariumSpecies , 1998, Applied and Environmental Microbiology.

[14]  T. Stachelhaus,et al.  Aminoacyl-CoAs as probes of condensation domain selectivity in nonribosomal peptide synthesis. , 1999, Science.

[15]  Jiachen Zi,et al.  Engineered production of fungal anticancer cyclooligomer depsipeptides in Saccharomyces cerevisiae. , 2013, Metabolic engineering.

[16]  T. Stachelhaus,et al.  Selective interaction between nonribosomal peptide synthetases is facilitated by short communication-mediating domains. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[17]  J. Nielsen,et al.  Implementation of communication-mediating domains for non-ribosomal peptide production in Saccharomyces cerevisiae. , 2010, Biotechnology and bioengineering.

[18]  D. Cane,et al.  Dissecting and exploiting intermodular communication in polyketide synthases. , 1999, Science.

[19]  N. Grammel,et al.  Construction and in vitro analysis of a new bi-modular polypeptide synthetase for synthesis of N-methylated acyl peptides. , 2000, Chemistry & biology.