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Issue 38, 2018
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Synthetic biology approaches and combinatorial biosynthesis towards heterologous lipopeptide production

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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

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Publication details

The article was received on 07 May 2018, accepted on 08 Aug 2018 and first published on 08 Aug 2018


Article type: Edge Article
DOI: 10.1039/C8SC02046A
Citation: Chem. Sci., 2018,9, 7510-7519
  • Open access: Creative Commons BY-NC license
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    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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