Issue 38, 2018

Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production

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.

Graphical abstract: Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production

Supplementary files

Article information

Article type
Edge Article
Submitted
07 May 2018
Accepted
08 Aug 2018
First published
08 Aug 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2018,9, 7510-7519

Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production

F. Yan, C. Burgard, A. Popoff, N. Zaburannyi, G. Zipf, J. Maier, H. S. Bernauer, S. C. Wenzel and R. Müller, Chem. Sci., 2018, 9, 7510 DOI: 10.1039/C8SC02046A

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