In work on polyketide biosynthesis, a combination of synthetic, enzymological,
and molecular genetic approaches is being used to clarify the intricate sequence
of events that is required to convert the simple building blocks acetate and
propionate to complex macrolides such as the broad spectrum antibiotic erythromycin
A and other antibiotics. In collaboration with Prof. Chaitan Khosla and his
group at Stanford, the mechanism of polyketide chain elongation has been studied
directly at the enzyme level using cloned 6-deoxyerythonolide B synthase and
various truncated mutants to establish the mechanistic and structural basis
for the programming of complex polyketide biosynthesis.