Cell free expression is a valuable way to circumvent bottlenecks that are introduced via lengthy genetic procedures. Efforts to further optimise and develop these systems include optimising for specific classes of natural products (e.g. polyketides or non-ribosomal peptides) or new host machineries. We are particularly interested in developing cell free systems for natural product production in Streptomyces and Myxobacteria. This has applications in high throughput bioengineering. For example, screening constructs in collaboration with computational scientists employing machine learning.

Heterologous expression is a powerful tool for accessing engineered pathways as well as pathways that are cryptic—or not produced under standard culture conditions.  Efforts in our lab aim to improve heterologous expression of natural products—both through developing better expression tools and through engineering new pathways.

We seek to characterise the enzymes in biosynthetic pathways. Our biggest focus is on the so called “megasynthase” enzymes, which are type I polyketide synthases and non-ribosomal peptide synthetases. These are complex, multidomain enzymes that have “colinear” biosynthetic pathways where in the molecular structure of metabolites correlates to sequence, enabling the ability to “genome mine” new natural products and recombine biosynthetic elements via protein chimeras.  Additionally, we characterise enzymes that are mechanistically novel or distinct.