Discovery and Engineering of Natural Products
Natural Product Biosynthesis
|
Soil bacteria are a classic source for isolating natural products, such as antibiotics and anticancer drugs. Typically, the genes that make these secondary metabolites are neatly organised together as biosynthetic gene clusters. However, many of these remain uncharacterised and are termed “cryptic” or “silent” due to their dormancy under laboratory cultivation. In the environment, unknown signals or stress factors are required to switch them on.
One current project is studying an uncharacterised natural product from Streptomyces, which specifically inhibits a recA- (DNA recombinase) mutant from B. subtilis, suggesting that this antimicrobial is targeting DNA as its mode of action. In collaboration with Dr Emzo de los Santos (University of Warwick) Funded by the Wellcome Trust and Royal Society 
|
Synthetic Biology
Synthetic biology enables the complete hardwiring of gene expression, using synthetic genes with optimised codon usage and the removal of natural regulatory elements. For awakening novel biosynthetic gene clusters, synthetic biology allows a way forward to remove “cryptic” control (e.g. operators, rare codons, poor start codons) that potentially limit gene expression and natural product biosynthesis. In synthetic biology this process is called refactoring, whereby genes and their control elements (e.g. promoters, RBS, terminators) can be restructured into synthetic operons. The group will assemble synthetic gene clusters to access new natural products, as well as identifying and confirming novel gene function.
Cell-Free Systems
There's been a recent explosion in cell-free research since the rise of synthetic biology. Cell-free systems allow quick design cycles for bottom-up design of prototype pathways and gene expression circuits. They contain all the machinery of a cell but behave like a chemical system in a test-tube. Cell-free systems can either contain an extract containing pathway enzymes or devices, or can be used for de novo synthesis of proteins within a few hours.
Research in the lab will focus on the use of cell-free systems for studying natural product biosynthesis and the development of “non-natural” natural products.
In collaboration with Dr Emzo de los Santos and Professor Chris Corre (University of Warwick)
Research in the lab will focus on the use of cell-free systems for studying natural product biosynthesis and the development of “non-natural” natural products.
In collaboration with Dr Emzo de los Santos and Professor Chris Corre (University of Warwick)
