Characterisation of novel glycoepetide antibiotic biosynthetic pathways

01.01.2017 bis 31.12.2018

The glycopeptide antibiotics (GPAs) are clinically relevant antibiotic natural products. These are complex molecules and their commercial production relies on the use of bacteria to produce these compounds. This project will
examine the mechanism of biosynthesis of two novel examples of the GPAs (ristomycin and kistamycin) by combining the strengths of the Stegmann group for in vivo manipulation of the bacterial producer strains with
the strengths of the Cryle group for in vitro characterisation of the biosynthetic enzymes (using structural biology and biochemical techniques). The complexity of the biosynthesis machinery requires that we understand their
function on a detailed level using in vitro techniques, however the overall pathway remains far too complex to reconstitute yet in vitro: hence the combination of in vitro experiments directly with the ability to examine the
effects of selective mutations in vivo will enable us to rapidly explore not only the biosynthesis of GPAs but also the potential to make new GPAs through redesign of the biosynthetic machinery itself.