Identification of a prodigiosin cyclization gene in the roseophilin producer and production of a new cyclized prodigiosin in a heterologous host.

Abstract

The prodigiosins are reddish-colored tripyrrole antibiotics biosynthesized by several microorganisms such as Serratia,1 Pseudomonas2 and Streptomyces.3 Streptomyces griseoviridis 2464-S5 produces prodigiosin R14 and roseophilin,5 a unique prodigiosin-related compound containing two pyrrole and one furan moieties (Figure 1), and carries the rph gene cluster involved in their biosynthesis.6 Prodigiosin R1 and roseophilin possess an alkyl chain with the same length and differ in the cyclization pattern (Figure 1). Twenty-one of 25 genes in the rph cluster are homologous to red genes in Streptomyces coelicolor A3(2),7 which produces undecylprodiginine3 and butyl-meta-cycloheptylprodiginine (streptorubin B).8 In the rph cluster, rphG, rphG2, rphG3 and rphG4 showed sufficient homology to redG, a gene involved in cyclization of undecylprodiginine to butyl-meta-cycloheptylprodiginine.9 Thus, we attempted to analyze the functions of these rph genes using a heterologous expression system in S. coelicolor.