The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110
Wolf T, Droste J, Gren T, Ortseifen V, Schneiker-Bekel S, Zemke T, Pühler A, Kalinowski J (2017)
BMC Genomics 18(1): 562.
Zeitschriftenaufsatz
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Einrichtung
Abstract / Bemerkung
Background
Acarbose is used in the treatment of diabetes mellitus type II and is produced by Actinoplanes sp. SE50/110. Although the biosynthesis of acarbose has been intensively studied, profound knowledge about transcription factors involved in acarbose biosynthesis and their binding sites has been missing until now. In contrast to acarbose biosynthetic gene clusters in Streptomyces spp., the corresponding gene cluster of Actinoplanes sp. SE50/110 lacks genes for transcriptional regulators.
Results
The acarbose regulator C (AcrC) was identified through an in silico approach by aligning the LacI family regulators of acarbose biosynthetic gene clusters in Streptomyces spp. with the Actinoplanes sp. SE50/110 genome. The gene for acrC, located in a head-to-head arrangement with the maltose/maltodextrin ABC transporter malEFG operon, was deleted by introducing PCR targeting for Actinoplanes sp. SE50/110. Characterization was carried out through cultivation experiments, genome-wide microarray hybridizations, and RT-qPCR as well as electrophoretic mobility shift assays for the elucidation of binding motifs. The results show that AcrC binds to the intergenic region between acbE and acbD in Actinoplanes sp. SE50/110 and acts as a transcriptional repressor on these genes. The transcriptomic profile of the wild type was reconstituted through a complementation of the deleted acrC gene. Additionally, regulatory sequence motifs for the binding of AcrC were identified in the intergenic region of acbE and acbD. It was shown that AcrC expression influences acarbose formation in the early growth phase. Interestingly, AcrC does not regulate the malEFG operon.
Conclusions
This study characterizes the first known transcription factor of the acarbose biosynthetic gene cluster in Actinoplanes sp. SE50/110. It therefore represents an important step for understanding the regulatory network of this organism. Based on this work, rational strain design for improving the biotechnological production of acarbose can now be implemented.
Stichworte
Actinoplanes;
Acarbose;
MalR;
AcrC;
Transcriptional regulation;
Actinomycetes
Erscheinungsjahr
2017
Zeitschriftentitel
BMC Genomics
Band
18
Ausgabe
1
Art.-Nr.
562
ISSN
1471-2164
eISSN
1471-2164
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Deutsche Forschungsgemeinschaft und die Universität Bielefeld gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2913116
Zitieren
Wolf T, Droste J, Gren T, et al. The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110. BMC Genomics. 2017;18(1): 562.
Wolf, T., Droste, J., Gren, T., Ortseifen, V., Schneiker-Bekel, S., Zemke, T., Pühler, A., et al. (2017). The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110. BMC Genomics, 18(1), 562. https://doi.org/10.1186/s12864-017-3941-x
Wolf, Timo, Droste, Julian, Gren, Tetiana, Ortseifen, Vera, Schneiker-Bekel, Susanne, Zemke, Till, Pühler, Alfred, and Kalinowski, Jörn. 2017. “The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110”. BMC Genomics 18 (1): 562.
Wolf, T., Droste, J., Gren, T., Ortseifen, V., Schneiker-Bekel, S., Zemke, T., Pühler, A., and Kalinowski, J. (2017). The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110. BMC Genomics 18:562.
Wolf, T., et al., 2017. The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110. BMC Genomics, 18(1): 562.
T. Wolf, et al., “The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110”, BMC Genomics, vol. 18, 2017, : 562.
Wolf, T., Droste, J., Gren, T., Ortseifen, V., Schneiker-Bekel, S., Zemke, T., Pühler, A., Kalinowski, J.: The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110. BMC Genomics. 18, : 562 (2017).
Wolf, Timo, Droste, Julian, Gren, Tetiana, Ortseifen, Vera, Schneiker-Bekel, Susanne, Zemke, Till, Pühler, Alfred, and Kalinowski, Jörn. “The MalR type regulator AcrC is a transcriptional repressor of acarbose biosynthetic genes in Actinoplanes sp. SE50/110”. BMC Genomics 18.1 (2017): 562.
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Daten bereitgestellt von European Bioinformatics Institute (EBI)
2 Zitationen in Europe PMC
Daten bereitgestellt von Europe PubMed Central.
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Teil dieser Dissertation
Analysis of the transcriptional regulation of the acarbose biosynthesis gene cluster in Actinoplanes sp. SE50/110
Droste J (2021)
Bielefeld: Universität Bielefeld.
Droste J (2021)
Bielefeld: Universität Bielefeld.
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