Biosynthetic Gene Clusters of Benzoisochromanequinone Antibiotics in Streptomyces spp. Identification of Genes Involved in Post-PKS Tailoring Steps.

Abstract

Benzoisochromanequinone (BIQ) antibiotics are a class of aromatic polyketides produced by Streptomyces spp. A polyketide synthase (PKS, Type II) is involved in the formation of each BIQ chromophore. The first PKS genes were cloned in S. coelicolor A3(2), producer of the typical BIQ antibiotic, actinorhodin; sequence analysis of the PKS genes revealed their clustering with all the other relevant biosynthetic genes (the act cluster). A number of PKS genes have been discovered in the producers not only of other BIQs, but also of other classes of aromatic polyketides, using the act PKS genes as hybridisation probes. Among them similar genetic organisations were identified for the genes encoding the minimal PKS components -KS (ketosynthase), CLF (chain length factor), ACP (acyl carrier protein)- and their closely associated proteins: KR (ketoreductase), ARO (aromatase), and CYC (cyclase). In spite of the increasing knowledge of PKS genes themselves, various biosynthetic problems remain to be solved. As one of the most extensively studied examples at the genetic level, BIQ antibiotics are useful model compounds to be studied to understand the whole biosynthetic pathways of aromatic polyketides. This review describes the genes from the act and gra (granaticin biosynthetic gene cluster in S. violaceoruber Tü22) clusters involved in post-PKS modifying (tailoring) steps to complete BIQ biosynthesis.