Characterization of the biosynthesis gene cluster for alkyl-O-dihydrogeranyl-methoxyhydroquinones in Actinoplanes missouriensis.

A polyketide biosynthesis gene cluster (agq) was found on the genome of a rare actinomycete, Actinoplanes missouriensis. Streptomyces lividans expressing agqA encoding a type III polyketide synthase produced alkylresorcinols mainly from C(16-17) fatty acids. Heterologous expression of the agq genes in S. lividans indicated the function of cognate polyketide modification enzymes; a monooxygenase AgqB hydroxylates the alkylresorcinols to yield 6-alkyl-2-hydroxyhydroquinones, a methyltransferase AgqC catalyzes O-methylation of the alkyl-hydroxyhydroquinones to yield 6-alkyl-2-methoxyhydroquinones, and a UbiA-like prenyltransferase AgqD attaches a prenyl group to the C-4 hydroxy group of the alkyl-methoxyhydroquinones to yield 6-alkyl-4-O-geranyl-2-methoxyhydroquinones and 6-alkyl-4-O-dihydrofarnesyl-2-methoxyhydroquinones derived from C(16-17) fatty acids. In contrast, A. missouriensis was found to produce 6-alkyl-4-O-dihydrogeranyl-2-methoxyhydroquinones derived from C(16-18) fatty acids by the function of the agq gene cluster. All of these prenylated phenolic lipids were novel compounds.