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A TetR-family transcription factor regulates fatty acid metabolism in the archaeal model organism Sulfolobus acidocaldarius.


ABSTRACT: Fatty acid metabolism and its regulation are known to play important roles in bacteria and eukaryotes. By contrast, although certain archaea appear to metabolize fatty acids, the regulation of the underlying pathways in these organisms remains unclear. Here, we show that a TetR-family transcriptional regulator (FadRSa) is involved in regulation of fatty acid metabolism in the crenarchaeon Sulfolobus acidocaldarius. Functional and structural analyses show that FadRSa binds to DNA at semi-palindromic recognition sites in two distinct stoichiometric binding modes depending on the operator sequence. Genome-wide transcriptomic and chromatin immunoprecipitation analyses demonstrate that the protein binds to only four genomic sites, acting as a repressor of a 30-kb gene cluster comprising 23 open reading frames encoding lipases and ?-oxidation enzymes. Fatty acyl-CoA molecules cause dissociation of FadRSa binding by inducing conformational changes in the protein. Our results indicate that, despite its similarity in overall structure to bacterial TetR-family FadR regulators, FadRSa displays a different acyl-CoA binding mode and a distinct regulatory mechanism.

SUBMITTER: Wang K 

PROVIDER: S-EPMC6449355 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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A TetR-family transcription factor regulates fatty acid metabolism in the archaeal model organism Sulfolobus acidocaldarius.

Wang Kun K   Sybers David D   Maklad Hassan Ramadan HR   Lemmens Liesbeth L   Lewyllie Charlotte C   Zhou Xiaoxiao X   Schult Frank F   Bräsen Christopher C   Siebers Bettina B   Valegård Karin K   Lindås Ann-Christin AC   Peeters Eveline E  

Nature communications 20190404 1


Fatty acid metabolism and its regulation are known to play important roles in bacteria and eukaryotes. By contrast, although certain archaea appear to metabolize fatty acids, the regulation of the underlying pathways in these organisms remains unclear. Here, we show that a TetR-family transcriptional regulator (FadR<sub>Sa</sub>) is involved in regulation of fatty acid metabolism in the crenarchaeon Sulfolobus acidocaldarius. Functional and structural analyses show that FadR<sub>Sa</sub> binds t  ...[more]

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