Thumbnail Image
Publication

Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production.

Yan, Fu
; 
Burgard, Christian
; 
Popoff, Alexander
; 
Zaburannyi, Nestor
; 
Zipf, Gregor
; 
Maier, Josef
; 
Bernauer, Hubert S
; 
Wenzel, Silke C
; 
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2018-10-14
Submitted date
Show all metadata
Files
Thumbnail Image
Open Access publication
Adobe PDF, 1.26 MB
Thumbnail Image
supplemental material
Adobe PDF, 4.99 MB
Other Titles
Abstract
Synthetic 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.
Citation
Affiliation
HIPS, Helmholtz-Institut füt Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
Publisher
Journal
URI
http://hdl.handle.net/10033/621529
DOI
10.1039/c8sc02046a
PubMed ID
30319751
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
Description
Series/Report no.
ISSN
2041-6520
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 3.0 United States
cbn
Collections
publications of the research group of microbial natural substances([HIPS]MINS)