Events and seminars

The Moore cell-free synthetic biology group has a broad interest in natural product biosynthesis and antimicrobial resistance. In this talk, I aim to discuss the relative strengths and limitations of the emerging use of cell-free systems within academic and industrial engineering biology research.

First, I will share our recent research on the biosynthesis of two distinct natural product pathways where we are leveraging the strengths of both cell-free and microbial cell approaches to elucidate enzyme function, as well as engineer biosynthesis. Specifically, I will share our findings on uncovering several new enzymes involved in modified indole biosynthesis, as well as engineering over 20 new-to-nature indolocarbazole natural products, with potential applications for biomedicine or sustainable pigments.

Second, our group has a major focus on developing bacterial cell-free gene expression systems for rapid and combinatorial engineering of peptide, protein, and small molecule biosynthesis^1–4, where we are collaborating with UK Health Security Agency and industry (e.g., Syngenta), for combating human and crop diseases, respectively. A significant part of the talk will discuss our recent development of using cell-free systems as a tool to elucidate antibiotic resistance in disease-causing bacteria, as well as the potential of developing non-standard antimicrobials⁵.

References

1.    Li, J., Kwon, Y.-C., Lu, Y. & Moore, S. J. Editorial: Cell-Free Synthetic Biology. Front Bioeng Biotechnol 9, 799122 (2021).

2.    Moore, S. J., Lai, H.-E., Li, J. & Freemont, P. S. Streptomyces cell-free systems for natural product discovery and engineering. Nat. Prod. Rep. (2022) doi:10.1039/d2np00057a.

3.    Nagappa, L. K. et al. A ubiquitous amino acid source for prokaryotic and eukaryotic cell-free transcription-translation systems. Front. Bioeng. Biotechnol. 10, 992708 (2022).

4.    Moore, S. J. et al. A Streptomyces venezuelae Cell-Free Toolkit for Synthetic Biology. ACS Synth. Biol. 10, 402–411 (2021).

5.    Chengan, K. et al. A cell-free strategy for host-specific profiling of intracellular antibiotic sensitivity and resistance. npj Antimicrobials and Resistance (2023) doi:10.1038/s44259-023-00018-z.