Regulation of bacterial haem biosynthesis

Beas, Jordi Zamarreño; Videira, Marco A.M.; Saraiva, Lı́gia M.

doi:10.1016/j.ccr.2021.214286

Cited by 17 publications

(13 citation statements)

References 191 publications

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“…In the cyanobacterium Thermosynechococcus elongatus ferrochelatase interacts with proto'gen IX oxidase; in Vibrio vulnificus a complex between ferrochelatase and proto'gen IX dehydrogenase was described; in B. subtilis, CpfC ferrochelatase co-purifies with Fra, a homolog of the eukaryotic iron chaperon frataxin; and in S. aureus there is a transient interaction between ferrochelatase and coproheme decarboxylase ChdC. Also in S. aureus, ferrochelatase CpfC was shown to interact with heme oxygenase IsdG of the heme uptake system (Reniere, Haley, and Skaar 2011;Videira et al 2018;Zamarreño Beas et al 2022). In this work, we provide evidence for the interaction of ferrochelatase and transfer of heme to a novel type of heme chaperone.…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted March 30, 2023. ; https://doi.org/10.1101/2023.03.30.534706 doi: bioRxiv preprint pathways share as the first common precursor the 5-aminolevulinic acid (ALA) molecule, that is converted to uroporphyrinogen III (uro'gen III) through the action of three enzymes: PbgS, HmbS and UroS (Heinemann, Jahn, and Jahn 2008). The following conversion of uro'gen III to heme occurs according to one of three pathways depending on the organism, which are described in detail in several reviews (e.g., Dailey and Medlock 2022;Zamarreño Beas, Videira, and Saraiva 2022).…”

Section: Introductionmentioning

confidence: 99%

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InCampylobacter jejunia new type of chaperone receives hemebfrom ferrochelatase

Beas

Videira

Karavaeva

et al. 2023

Preprint

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Intracellular heme formation and trafficking are fundamental processes in living organisms. Three biogenesis pathways are used by bacteria and archaea to produce iron protoporphyrin IX (heme b) that diverge after the formation of the common intermediate uroporphyrinogen III (uro'gen III). In this work, we identify and provide a detailed characterization of the enzymes involved in the transformation of uro'gen III into heme. We show that in this organism operates the protoporphyrin-dependent pathway (PPD pathway), in which the last reaction is the incorporation of ferrous iron into the porphyrin ring by the ferrochelatase enzyme. In general, following this final reaction, little is known about how the formed heme b reaches the target proteins. In particular, the chaperons that are thought to be required to traffic heme for incorporation into hemeproteins to avoid the cytotoxicity associated to free heme, remain largely unidentified. We identified in C. jejuni a chaperon-like protein, named CgdH2, that binds heme with a dissociation constant of 4.9 ± 1.0 μM, a binding that is impaired upon mutation of residues histidine 45 and 133. We show that C. jejuni CgdH2 establishes protein-protein interactions with ferrochelatase, which should enable for the observed transfer of heme from ferrochelatase to CgdH2. Phylogenetic analysis revealed that C. jejuni CgdH2 is evolutionarily distinct from the currently known chaperones. Therefore, CgdH2 is a novel chaperone and the first protein identified as an acceptor of the intracellularly formed heme, thus enlarging our understanding of bacterial heme homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

InCampylobacter jejunia new type of chaperone receives hemebfrom ferrochelatase

Beas

Videira

Karavaeva

et al. 2023

Preprint

Self Cite

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“…Several of the bacteria that have been discussed are facultative anaerobes, making oxygen availability central to the regulation of heme biosynthesis as heme is needed for aerobic respiration and protection from ROS, and for many Gram-negative bacteria, oxygen availability is a common regulator of heme biosynthesis ( Dailey et al, 2017 ; Zamarreño Beas et al, 2022 ). Both L. monocytogenes and S. aureus have been classified as facultative anaerobes, and while B. subtilis was originally considered to be strictly aerobic, it has since been discovered to use nitrate as an electron acceptor for growth in anaerobic conditions, making it a likely facultative anaerobe ( Hoffmann et al, 1995 ).…”

Section: Regulation Of Heme Synthesis Via the Coproporphyrin Dependen...mentioning

confidence: 99%

Regulation of heme biosynthesis via the coproporphyrin dependent pathway in bacteria

Aftab,

Donegan

2024

Front. Microbiol.

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Heme biosynthesis in the Gram-positive bacteria occurs mostly via a pathway that is distinct from that of eukaryotes and Gram-negative bacteria in the three terminal heme synthesis steps. In many of these bacteria heme is a necessary cofactor that fulfills roles in respiration, gas sensing, and detoxification of reactive oxygen species. These varying roles for heme, the requirement of iron and glutamate, as glutamyl tRNA, for synthesis, and the sharing of intermediates with the synthesis of other porphyrin derivatives necessitates the need for many points of regulation in response to nutrient availability and metabolic state. In this review we examine the regulation of heme biosynthesis in these bacteria via heme, iron, and oxygen species. We also discuss our perspective on emerging roles of protein-protein interactions and post-translational modifications in regulating heme biosynthesis.

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“…Heme is an iron-containing porphyrin compound that is essential for the survival of virtually all living systems (Gallio et al 2021 ). It serves as a prosthetic group in proteins involved in multiple biological processes, such as oxygen transport and storage, electron transfer, and oxidative stress detoxification (Beas et al 2022 ). Heme has extensive application value.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in microbial synthesis of free heme

Yang,

Guo,

Sun

et al. 2024

Appl Microbiol Biotechnol

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Heme is an iron-containing porphyrin compound widely used in the fields of healthcare, food, and medicine. Compared to animal blood extraction, it is more advantageous to develop a microbial cell factory to produce heme. However, heme biosynthesis in microorganisms is tightly regulated, and its accumulation is highly cytotoxic. The current review describes the biosynthetic pathway of free heme, its fermentation production using different engineered bacteria constructed by metabolic engineering, and strategies for further improving heme synthesis. Heme synthetic pathway in Bacillus subtilis was modified utilizing genome-editing technology, resulting in significantly improved heme synthesis and secretion abilities. This technique avoided the use of multiple antibiotics and enhanced the genetic stability of strain. Hence, engineered B. subtilis could be an attractive cell factory for heme production. Further studies should be performed to enhance the expression of heme synthetic module and optimize the expression of heme exporter and fermentation processes, such as iron supply. Key points • Strengthening the heme biosynthetic pathway can significantly increase heme production. • Heme exporter overexpression helps to promote heme secretion, thereby further promoting excessive heme synthesis. • Engineered B. subtilis is an attractive alternative for heme production.

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Regulation of bacterial haem biosynthesis

Cited by 17 publications

References 191 publications

InCampylobacter jejunia new type of chaperone receives hemebfrom ferrochelatase

InCampylobacter jejunia new type of chaperone receives hemebfrom ferrochelatase

Regulation of heme biosynthesis via the coproporphyrin dependent pathway in bacteria

Recent advances in microbial synthesis of free heme

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