Article: Biocatalytic production of the antibiotic aurachin D in Escherichia coli.
2022 Volume 12, Issue 1, Page(s) 138
Abstract: Aurachin D is a potent inhibitor of cytochrome bd oxidases, which are potential targets in the treatment of infectious diseases. In this study, our aim was to improve the biocatalytic production of aurachin D from a quinolone precursor molecule with ... ...
| Abstract | Aurachin D is a potent inhibitor of cytochrome bd oxidases, which are potential targets in the treatment of infectious diseases. In this study, our aim was to improve the biocatalytic production of aurachin D from a quinolone precursor molecule with recombinant Escherichia coli cells expressing the biosynthesis enzyme AuaA. In order to achieve a high-level production of this membrane-bound farnesyltransferase in E. coli, the expression of the auaA gene was translationally coupled to an upstream cistron in accordance with a bicistronic design (BCD) strategy. Screening of various BCD elements led to the identification of optimized auaA expression cassettes, which increased the aurachin D titer in E. coli up to 29-fold in comparison to T7-mediated expression. This titer could be further raised by codon optimization of auaA and by introducing the mevalonate pathway into the production strain. The latter measure was intended to improve the availability of farnesyl pyrophosphate, which is needed as a cosubstrate for the AuaA-catalyzed reaction. In sum, the described efforts resulted in a strain producing aurachin D with a titer that is 424 times higher than that obtained with the original, non-optimized expression host. |
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| Language | English |
| Publishing date | 2022-11-03 |
| Publishing country | Germany |
| Document type | Journal Article |
| ZDB-ID | 2621432-5 |
| ISSN | 2191-0855 |
| ISSN | 2191-0855 |
| DOI | 10.1186/s13568-022-01478-8 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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