Structures of an unusual 3-hydroxyacyl dehydratase (FabZ) from a ladderane-producing organism with an unexpected substrate preference

Dietl, Andreas; Wellach, Kathrin; Mahadevan, Pavithra; Mertes, Nicole; Winter, Sophie L.; Kutsch, Tobias; Walz, Carlo; Schlichting, Ilme; Fabritz, Sebastian; Barends, ThomasR.M.

doi:10.1016/j.jbc.2023.104602

Cited by 3 publications

(1 citation statement)

References 54 publications

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“…Furthermore, we speculate that the observed unprecedented decrease of C16 alkyls in this study not matching the homeoviscous adaptation theory may be the result of ladderanes synthesis, specifically, that C16 alkyls or their parts could be used as an initial substrate for ladderane synthesis by a recently discovered anammox-specific acyl carrier protein and ACP-3hydroxyacyl dehydratase (Dietl and Barends, 2022;Dietl et al, 2023). However, anammox were found to cope with temperatures as high as 80 °C (Byrne et al, 2009), which implies the existence of another adaptation mechanism to cover these extremely thermophilic temperatures.…”

Section: Discontinuous Nature Of Anammox Adaptation Via Ladderanesmentioning

confidence: 69%

Mechanisms of Anammox Adaptation to High Temperatures: Increased Cyclization of Ladderane Lipids and Proteomic Insights

Christina,

Klára,

Adam

et al. 2024

Preprint

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Although anammox-based processes have been widely applied in mesophilic conditions of reject water and recently in mainstream conditions, the potential of their implementation in high-temperature wastewaters remains largely unexplored. Therefore, this study investigated the operation parameters for the successful adaptation of anammox bacteria and the mechanisms involved on the proteomic and cellular level including unique ladderane lipids. For this purpose, the enrichment of Candidatus Brocadia was cultivated in two fed-batch reactors (FBRs) at a lab scale. The temperature of one FBR was gradually increased from 30 to 40 degrees C while the other FBR was maintained at 30 degrees C with four consecutive replicates of this experiment. For this adaptation to be successful, the original loading rate had to be at least halved, or ideally maintained below half the value of the specific anammox activity at the time. The most notable adaptation mechanisms included: (1) upregulation of chaperones and (2) doubled ladderane cyclization via the replacement of non-ladderane fatty acid by a ladderane fatty acid in ladderane lipids (p-value 0.005). To our best knowledge, this is the first study to describe the novel mechanism of ladderane cyclization which together with other adaptation strategies presents crucial indicators in anammox adaptation to high-temperature wastewaters.

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Section: Discontinuous Nature Of Anammox Adaptation Via Ladderanesmentioning

confidence: 69%

Mechanisms of Anammox Adaptation to High Temperatures: Increased Cyclization of Ladderane Lipids and Proteomic Insights

Christina,

Klára,

Adam

et al. 2024

Preprint

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Structural Basis of the Dehydratase Module (hDH) of Human Fatty Acid Synthase

Cai,

Huang,

Zhang

et al. 2024

ChemBioChem

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The human fatty acid synthase (hFASN) produces fatty acids for cellar membrane construction, energy storage, biomolecule modifications and signal transduction. Abnormal expression and functions of hFASN highly associate with numerous human diseases such as obesity, diabetes, and cancers, and thereby it has been considered as a valuable potential drug target. So far, the structural and catalytic mechanisms of most of the hFASN enzymatic modules have been extensively studied, except the key dehydratase module (hDH). Here we presented the enzymatic characterization and the high‐resolution crystal structure of hDH. We demonstrated that the hDH preferentially catalyzes the acyl substrates with short lengths between 4 to 8‐carbons, and exhibits much lower enzymatic activity on longer substrates. Subsequent structural study showed that hDH displays a pseudo‐dimeric organization with a single L‐shaped composite hydrophobic catalytic tunnel as well as an atypical ACP binding site nearby, indicating that hDH achieves distinct substrate recognition and dehydration mechanisms compared to the conventional bacterial fatty acid dehydratases identified. Our findings laid the foundation for understanding the biological and pathogenic functions of hFASN, and may facilitate therapeutical drug development against diseases with abnormal functionality of hFASN.

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Biosynthetic potential of uncultured anammox community bacteria revealed through multi-omics analysis

Wang,

Fu,

Shen

et al. 2024

Bioresource Technology

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Structures of an unusual 3-hydroxyacyl dehydratase (FabZ) from a ladderane-producing organism with an unexpected substrate preference

Cited by 3 publications

References 54 publications

Mechanisms of Anammox Adaptation to High Temperatures: Increased Cyclization of Ladderane Lipids and Proteomic Insights

Mechanisms of Anammox Adaptation to High Temperatures: Increased Cyclization of Ladderane Lipids and Proteomic Insights

Structural Basis of the Dehydratase Module (hDH) of Human Fatty Acid Synthase

Biosynthetic potential of uncultured anammox community bacteria revealed through multi-omics analysis

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