Functional Complementation of Pyran Ring Formation in Actinorhodin Biosynthesis in Streptomyces coelicolorA3(2) by Ketoreductase Genes for Granaticin Biosynthesis

@article{Ichinose2001FunctionalCO,
  title={Functional Complementation of Pyran Ring Formation in Actinorhodin Biosynthesis in Streptomyces coelicolorA3(2) by Ketoreductase Genes for Granaticin Biosynthesis},
  author={K. Ichinose and T. Taguchi and D. Bedford and Y. Ebizuka and D. Hopwood},
  journal={Journal of Bacteriology},
  year={2001},
  volume={183},
  pages={3247 - 3250}
}
ABSTRACT A mutation in actVI-ORF1, which controls C-3 reduction in actinorhodin biosynthesis by Streptomyces coelicolor, was complemented by gra-ORF5 and -ORF6 from the granaticin biosynthetic gene cluster of Streptomyces violaceoruberTü22. It is hypothesized that, while gra-ORF5 alone is a ketoreductase for C-9, gra-ORF6 gives the enzyme regiospecificity also for C-3. 
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It is demonstrated that med-ORF12 encodes a ketoreductase responsible for the enantioselective reduction at C-3 in the formation of the pyran ring. Expand
Remarkably different structures and reaction mechanisms of ketoreductases for the opposite stereochemical control in the biosynthesis of BIQ antibiotics.
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Two ketoreductases are involved in the biosynthesis of actinorhodin in Streptomyces coelicolor A3(2) and dihydrogranaticin in S. violaceoruber Tu22, although there is no similarity between their amino acid sequences. Expand
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TLDR
Pyran ring formation in the biosynthesis of actinorhodin in Streptomyces coelicolor A3 was studied using the act cluster deficient strain, CH999, carrying pRM5-based plasmids harbouring combinations of the actVI genes, suggesting that the act VI-ORF1 product is a reductase determining the C-3 stereochemical centre. Expand
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One member of each mutant class was mapped unambigiguously to the chromosomal linkage map in the short segment between the hisD and guaA loci, suggesting that structural genes for actinorhodin biosynthesis may form an uninterrupted cluster of chromosomal genes. Expand
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Putative functional assignments of the products of most of the newly discovered ORFs were made, including those of genes involved in the PKS and tailoring Steps in the biosynthesis of the granaticin aglycone, steps in the deoxy sugar pathway, and putative regulatory and export functions. Expand
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TLDR
The genes from the act and gra (granaticin biosynthetic gene cluster in S. violaceoruber Tu22) clusters involved in post-PKS modifying (tailoring) steps to complete BIQ biosynthesis are described. Expand
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