43(P-3) ベンゾイソクロマンキノン系抗生物質生合成の反応と制御に関する研究 : 遺伝子解析からのアプローチ(ポスター発表の部)

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Benzoisochromanequinone (BIQ) antibiotics are a class of aromatic polyketides produced by Streptonzyces spp. Actinorhodin (ACT) produced by Streptomyces coelicolor A3(2) has served as one of the pioneering model compounds for studying the genetic programming of aromatic polyketides whose basic carbon skeleton is formed by a type II polyketide synthase. Elucidation of the biosynthetic pathway of ACT would lead to comprehensive understanding of secondary metabolism because S. coelicolor is currently the subject of a genome sequencing project. The present study focuses on the BIQs, the granaticins (GRAs), whose nascent polyketide is identical to that of ACT. The post-PKS steps involve different pyran-ring stereochemistry and glycosylation. Comparison of the complete gene clusters for ACT and GRA is therefore of great interest. The entire GRA biosynthetic gene cluster was cloned from S. violaceoruber Tu22, and expressed in the heterologous host, S. coelicolor A3(2) strain CH999. Chemical analysis of the recombinants carrying the cosmid, pOJ446-22-24, showed comparable production of GRAs. Sequencing analysis of the cosmid identified 37 complete open reading frames (ORFs). There are 15 ORFs that resemble each other on the act and gra clusters. Although the fact that granaticin has the opposite stereochemistry from ACT led us to search for the gra homologues for actVI-ORF1, the stereochemical determinant at C-3 of ACT, the gra cluster lacks obvious candidates. There exist gra ORF products having a characteristic nucleotide binding motif: ORFs 5,6,17,22, and 26. The products of ORFs 17, 22, and 26 are most likely to be involved in the DOH pathway because of their high degree of homologies with other deduced gene products responsible for deoxysugar formation. An explored possibility is that the stereochemistry in the pyran ring of GRA biosynthesis would be controlled by ORF 5/6. A pathway-specific transcriptional activator gene (gra-ORF9) was identified. The gene product (named SARP: Streptomyces antibiotic regulatory protein) is presumed to bind the direct repeat (DR) sequences in the promoter regions of Streptomyces antibiotic biosynthetic genes. A search for such DR sequences in the gra cluster revealed an array of hexameric repeats separated by fixed numbers of nucleotides corresponding one or two turns of the DNA helices.
天然有機化合物討論会の論文
2000-10-01

43(P-3) ベンゾイソクロマンキノン系抗生物質生合成の反応と制御に関する研究 : 遺伝子解析からのアプローチ(ポスター発表の部)

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