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Structural insights into repression of the Pneumococcal fatty acid synthesis pathway by repressor FabT and co-repressor acyl-ACP.

Zuo G, Chen ZP, Jiang YL, Zhu Z, Ding C, Zhang Z, Chen Y, Zhou CZ, Li Q
FEBS Lett 593 2730-2741 (2019)
Cited: 10 times
EuropePMC logo PMID: 31291684

Abstract

The Streptococcus pneumoniae fatty acid synthesis (FAS) pathway is globally controlled at the transcriptional level by the repressor FabT and its co-repressor acyl carrier protein (acyl-ACP), the intermediate of phospholipid synthesis. Here, we report the crystal structure of FabT complexed with a 23-bp dsDNA, which indicates that FabT is a weak repressor with low DNA-binding affinity in the absence of acyl-ACP. Modification of ACP with a long-chain fatty acid is necessary for the formation of a stable complex with FabT, mimicked in vitro by cross-linking, which significantly elevates the DNA-binding affinity of FabT. Altogether, we propose a putative working model of gene repression under the double control of FabT and acyl-ACP, elucidating a distinct repression network for Pneumococcus to precisely coordinate FAS.

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Reviews citing this publication (1)

  1. FabT, a Bacterial Transcriptional Repressor That Limits Futile Fatty Acid Biosynthesis. Lambert C, Poyart C, Gruss A, Fouet A. Microbiol Mol Biol Rev 86 e0002922 (2022)

Articles citing this publication (7)

  1. Genome Sequencing and Analysis of Thraustochytriidae sp. SZU445 Provides Novel Insights into the Polyunsaturated Fatty Acid Biosynthesis Pathway. Zhu X, Li S, Liu L, Li S, Luo Y, Lv C, Wang B, Cheng CHK, Chen H, Yang X. Mar Drugs 18 E118 (2020)
  2. The Enterococcus faecalis FabT Transcription Factor Regulates Fatty Acid Biosynthesis in Response to Exogeneous Fatty Acids. Zou Q, Dong H, Zhu L, Cronan JE. Front Microbiol 13 877582 (2022)
  3. Transcriptional Profiling Reveals the Importance of RcrR in the Regulation of Multiple Sugar Transportation and Biofilm Formation in Streptococcus mutans. Gong T, He X, Chen J, Tang B, Zheng T, Jing M, Lin Y, Pan Y, Ma Q, Li Y, Zhou X. mSystems 6 e0078821 (2021)
  4. Competence-Associated Peptide BriC Alters Fatty Acid Biosynthesis in Streptococcus pneumoniae. Aggarwal SD, Gullett JM, Fedder T, Safi JPF, Rock CO, Hiller NL. mSphere 6 e0014521 (2021)
  5. Inactivation of Transcriptional Regulator FabT Influences Colony Phase Variation of Streptococcus pneumoniae. Zhang J, Ye W, Wu K, Xiao S, Zheng Y, Shu Z, Yin Y, Zhang X. mBio 12 e0130421 (2021)
  6. The Bactericidal Fatty Acid Mimetic 2CCA-1 Selectively Targets Pneumococcal Extracellular Polyunsaturated Fatty Acid Metabolism. Reithuber E, Nannapaneni P, Rzhepishevska O, Lindgren AEG, Ilchenko O, Normark S, Almqvist F, Henriques-Normark B, Mellroth P. mBio 11 e03027-20 (2020)
  7. Acyl-AcpB, a FabT corepressor in Streptococcus pyogenes. Lambert C, d'Orfani A, Gaillard M, Zhang Q, Gloux K, Poyart C, Fouet A. J Bacteriol 205 e0027423 (2023)


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