Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Bernauer, Hubert S
Wenzel, Silke C
MetadataShow full item record
AbstractSynthetic biology techniques coupled with heterologous secondary metabolite production offer opportunities for the discovery and optimisation of natural products. Here we developed a new assembly strategy based on type IIS endonucleases and elaborate synthetic DNA platforms, which could be used to seamlessly assemble and engineer biosynthetic gene clusters (BGCs). By applying this versatile tool, we designed and assembled more than thirty different artificial myxochromide BGCs, each around 30 kb in size, and established heterologous expression platforms using a derivative of Myxococcus xanthus DK1622 as a host. In addition to the five native types of myxochromides (A, B, C, D and S), novel lipopeptide structures were produced by combinatorial exchange of nonribosomal peptide synthetase (NRPS) encoding genes from different myxochromide BGCs. Inspired by the evolutionary diversification of the native myxochromide megasynthetases, the ancestral A-type NRPS was engineered by inactivation, deletion, or duplication of catalytic domains and successfully converted into functional B-, C- and D-type megasynthetases. The constructional design approach applied in this study enables combinatorial engineering of complex synthetic BGCs and has great potential for the exploitation of other natural product biosynthetic pathways.
AffiliationHIPS, Helmholtz-Institut füt Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States
- An Orphan MbtH-Like Protein Interacts with Multiple Nonribosomal Peptide Synthetases in Myxococcus xanthus DK1622.
- Authors: Esquilín-Lebrón KJ, Boynton TO, Shimkets LJ, Thomas MG
- Issue date: 2018 Nov 1
- Biosynthesis and Heterologous Production of Argyrins.
- Authors: Pogorevc D, Tang Y, Hoffmann M, Zipf G, Bernauer HS, Popoff A, Steinmetz H, Wenzel SC
- Issue date: 2019 May 17
- Combinatorial biosynthesis of cyclic lipopeptide antibiotics: a model for synthetic biology to accelerate the evolution of secondary metabolite biosynthetic pathways.
- Authors: Baltz RH
- Issue date: 2014 Oct 17
- An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides in <i>Escherichia coli</i>.
- Authors: Cleto S, Lu TK
- Issue date: 2017 Oct 10
- Novel expression hosts for complex secondary metabolite megasynthetases: Production of myxochromide in the thermopilic isolate Corallococcus macrosporus GT-2.
- Authors: Perlova O, Gerth K, Kuhlmann S, Zhang Y, Müller R
- Issue date: 2009 Jan 6