Rational Engineering of PKS Modules for Neoaureothin Derivatives Production

다국어 초록 (Multilingual Abstract)

Neoaureothin, rare nitro-substituted polyketide produced by Streptomyces orinoci, exhibits valuable biological activities including antiviral, antimalarial and nematicidal activities. However, because it has poor water solubility and only dissolves in organic solvents, there is a limit to its use. In this study, we produced neoaureothin derivatives having improved solubility with slightly modified structures by rational engineering to PKS (polyketide synthase) modules in neoaureothin BGC (biosynthetic gene cluster). To increase its solubility, we designed derivatives with hydroxyl group on its backbone structure. We deactivated dehydratase in norA’ modules in PKS to make derivatives have hydroxyl group. Furthermore, we designed another derivative, by deactivation of ketoreductase in norB module to modify tetrahydrofuran ring, for improved nematicidal bioactivity. After derivatives production, we expect that in vitro glycosylation can be conducted to the produced derivatives to make more soluble derivatives.