ArticleProceedings of the National Academy of Sciences of the United States of America2015
Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03450369 (A Phase 1B Dose Escalating Study of the Safety, Short-Term Engraftment and Action of a Singly-Applied NB01 in Adults With Moderate Acne), which is not on this map. Cited by 109 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1B Dose Escalating Study of the Safety, Short-Term Engraftment and Action of a Singly-Applied NB01 in Adults With Moderate Acne
Who cites it
109 citing papers in PubMed, 190 citations in OpenAlex.
- Unraveling the active site cover of coproheme decarboxylase from Listeria monocytogenes.The FEBS journal · 2026Article
- Use of Porphyrin Precursors as a Novel Approach for Detection ofInternational journal of molecular sciences · 2026Article
- Milestones in the Elucidation of Heme Biosynthesis.Chemical reviews · 2026Review
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway with Mycobacterium tuberculosis adaptation to nitric oxide and iron limitation stress.PLoS genetics · 2026Article
- SHP-1 agonist SC-43 limits methicillin-resistant Staphylococcus aureus infection through inhibition of heme biosynthesis.EMBO molecular medicine · 2026Article
- The terminal heme synthetic enzyme, coproheme decarboxylase, negatively regulates heme uptake in Mycobacterium tuberculosis.The Journal of biological chemistry · 2026Article
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway withbioRxiv : the preprint server for biology · 2026Article
- Bacterial porphyrins in healthy skin: Microbiota components impact melanogenesis and age-related processes leading to Porphyr'ageing.International journal of cosmetic science · 2026Article
- Porphyrin pathways as targets for combating antimicrobial resistance: virulence and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- The role of conserved elements in an active site α-helix of coproheme decarboxylase.Journal of inorganic biochemistry · 2026Article
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- Identification of SARS-CoV-2 3CLpro inhibitors from marine actinomycetes through integrated phylogeny-based metabolomics with functional screening and bioinformatic analysis.Scientific reports · 2025Article
- High-yield porphyrin production through metabolic engineering and biocatalysis.Nature biotechnology · 2025Article
- Deciphering the role of the distal pocket in Staphylococcus aureus coproheme decarboxylase.Journal of inorganic biochemistry · 2025Article
- Metabolic engineering ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Heme and immunity: The heme oxygenase dichotomy.Journal of inorganic biochemistry · 2025Review
- Compartmentalization of heme biosynthetic pathways into yeast mitochondria enhances heme production.NPJ science of food · 2025Article
- Functional Differentiation and Regulatory Mechanisms of Ferrochelatases HemH1 and HemH2 inInternational journal of molecular sciences · 2025Article
- Photodynamic Inactivation Mediated by Endogenous Porphyrins ofACS omega · 2025Article
- Mitochondrial translation regulates terminal erythroid differentiation by maintaining iron homeostasis.Science advances · 2025Article
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
It has been generally accepted that biosynthesis of protoheme (heme) uses a common set of core metabolic intermediates that includes protoporphyrin. Herein, we show that the Actinobacteria and Firmicutes (high-GC and low-GC Gram-positive bacteria) are unable to synthesize protoporphyrin. Instead, they oxidize coproporphyrinogen to coproporphyrin, insert ferrous iron to make Fe-coproporphyrin (coproheme), and then decarboxylate coproheme to generate protoheme. This pathway is specified by three genes named hemY, hemH, and hemQ. The analysis of 982 representative prokaryotic genomes is consistent with this pathway being the most ancient heme synthesis pathway in the Eubacteria. Our results identifying a previously unknown branch of tetrapyrrole synthesis support a significant shift from current models for the evolution of bacterial heme and chlorophyll synthesis. Because some organisms that possess this coproporphyrin-dependent branch are major causes of human disease, HemQ is a novel pharmacological target of significant therapeutic relevance, particularly given high rates of antimicrobial resistance among these pathogens.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.