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- W2155254049 abstract "Summary Jadomycin production is under complex regulation in S treptomyces venezuelae . Here, another cluster‐situated regulator, JadR *, was shown to negatively regulate jadomycin biosynthesis by binding to four upstream regions of jadY , jadR1 , jadI and jadE in jad gene cluster respectively. The transcriptional levels of four target genes of JadR * increased significantly in Δ jadR *, confirming that these genes were directly repressed by JadR *. Jadomycin B ( JdB ) and its biosynthetic intermediates 2,3‐dehydro‐ UWM 6 ( DHU ), dehydrorabelomycin ( DHR ) and jadomycin A ( JdA ) modulated the DNA ‐binding activities of JadR * on the jadY promoter, with DHR giving the strongest dissociation effects. Direct interactions between JadR * and these ligands were further demonstrated by surface plasmon resonance, which showed that DHR has the highest affinity for JadR *. However, only DHU and DHR could induce the expression of jadY and jadR * in vivo . JadY is the FMN / FAD reductase supplying cofactors FMNH 2 / FADH 2 for JadG , an oxygenase, that catalyses the conversion of DHR to JdA . Therefore, our results revealed that JadR * and early pathway intermediates, particularly DHR , regulate cofactor supply by a convincing case of a feed‐forward mechanism. Such delicate regulation of expression of jadY could ensure a timely supply of cofactors FMNH 2 / FADH 2 for jadomycin biosynthesis, and avoid unnecessary consumption of NAD ( P ) H ." @default.
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- W2155254049 date "2013-10-17" @default.
- W2155254049 modified "2023-10-03" @default.
- W2155254049 title "JadR*-mediated feed-forward regulation of cofactor supply in jadomycin biosynthesis" @default.
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- W2155254049 doi "https://doi.org/10.1111/mmi.12406" @default.
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