scholarly journals Heme auxotrophy in abundant aquatic microbial lineages

2021 ◽  
Vol 118 (47) ◽  
pp. e2102750118
Author(s):  
Suhyun Kim ◽  
Ilnam Kang ◽  
Jin-Won Lee ◽  
Che Ok Jeon ◽  
Stephen J. Giovannoni ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
De Novo ◽  
Heme Biosynthesis ◽  
Bacterial Group ◽  
Free Living ◽  
Freshwater Habitats ◽  
Domains Of Life ◽  
Living Organisms ◽  
Microbial Groups ◽  
Genome Analyses

Heme, a porphyrin ring complexed with iron, is a metalloprosthetic group of numerous proteins involved in diverse metabolic and respiratory processes across all domains of life, and is thus considered essential for respiring organisms. Several microbial groups are known to lack the de novo heme biosynthetic pathway and therefore require exogenous heme from the environment. These heme auxotroph groups are largely limited to pathogens, symbionts, or microorganisms living in nutrient-replete conditions, whereas the complete absence of heme biosynthesis is extremely rare in free-living organisms. Here, we show that the acI lineage, a predominant and ubiquitous free-living bacterial group in freshwater habitats, is auxotrophic for heme, based on the experimental or genomic evidence. We found that two recently cultivated acI isolates require exogenous heme for their growth. One of the cultured acI isolates also exhibited auxotrophy for riboflavin. According to whole-genome analyses, all (n = 20) isolated acI strains lacked essential enzymes necessary for heme biosynthesis, indicating that heme auxotrophy is a conserved trait in this lineage. Analyses of >24,000 representative genomes for species clusters of the Genome Taxonomy Database revealed that heme auxotrophy is widespread across abundant but not-yet-cultivated microbial groups, including Patescibacteria, Marinisomatota (SAR406), Actinomarinales (OM1), and Marine groups IIb and III of Euryarchaeota. Our findings indicate that heme auxotrophy is a more common phenomenon than previously thought, and may lead to use of heme as a growth factor to increase the cultured microbial diversity.

scholarly journals Heme auxotrophy in abundant aquatic microbial lineages

2021 ◽  
Author(s):  
Suhyun Kim ◽  
Ilnam Kang ◽  
Jin-Won Lee ◽  
Che-Ok Jeon ◽  
Stephen J. Giovannoni ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
De Novo ◽  
Heme Biosynthesis ◽  
Free Living ◽  
Group Iii ◽  
Freshwater Habitats ◽  
Domains Of Life ◽  
Living Organisms ◽  
Microbial Groups ◽  
Genome Analyses

Heme, a porphyrin ring complexed with iron, is a metalloprosthetic group of numerous proteins involved in diverse metabolic and respiratory processes across all domains of life, and is thus considered essential for respiring organisms1,2. Several microbial groups are known to lack the de novo heme biosynthetic pathway and therefore require exogenous heme from the environment3. These heme auxotroph groups are largely limited to pathogens4,5, symbionts6,7, or microorganisms living in nutrient-replete conditions8, whereas the complete absence of heme biosynthesis is extremely rare in free-living organisms9. Here, we show that the acI lineage, a predominant and ubiquitous free-living bacterial group in freshwater habitats, is auxotrophic for heme. We found that two recently cultivated acI isolates10 require exogenous heme for their growth. According to whole-genome analyses, all (n=20) isolated acI strains lacked essential enzymes necessary for heme biosynthesis, indicating that heme auxotrophy is a conserved trait in this lineage. Analyses of >24,000 representative genomes for species clusters of the Genome Taxonomy Database (GTDB) revealed that heme auxotrophy is widespread across abundant but not-yet-cultivated microbial groups, including Patescibacteria, Marinisomatota (SAR406), Actinomarinales (OM1), and marine group III Euryarchaeota. Our findings indicate that heme auxotrophy is a more common phenomenon than previously thought, and may lead to use of heme as a growth factor to increase the cultured microbial diversity.

scholarly journals A Novel Pathway for the Biosynthesis of Heme inArchaea: Genome-Based Bioinformatic Predictions and Experimental Evidence

Archaea ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Sonja Storbeck ◽  
Sarah Rolfes ◽  
Evelyne Raux-Deery ◽  
Martin J. Warren ◽  
Dieter Jahn ◽  
...  
Keyword(s):  
Experimental Verification ◽  
Biosynthetic Pathway ◽  
Gene Clusters ◽  
Methanosarcina Barkeri ◽  
Heme Biosynthesis ◽  
Alternative Route ◽  
Biological Processes ◽  
Prosthetic Group ◽  
Biosynthesis Gene ◽  
Domains Of Life

Heme is an essential prosthetic group for many proteins involved in fundamental biological processes in all three domains of life. InEukaryotaandBacteriaheme is formedviaa conserved and well-studied biosynthetic pathway. Surprisingly, inArchaeaheme biosynthesis proceedsviaan alternative route which is poorly understood. In order to formulate a working hypothesis for this novel pathway, we searched 59 completely sequenced archaeal genomes for the presence of gene clusters consisting of established heme biosynthetic genes and colocalized conserved candidate genes. Within the majority of archaeal genomes it was possible to identify such heme biosynthesis gene clusters. From this analysis we have been able to identify several novel heme biosynthesis genes that are restricted to archaea. Intriguingly, several of the encoded proteins display similarity to enzymes involved in hemed1biosynthesis. To initiate an experimental verification of our proposals twoMethanosarcina barkeriproteins predicted to catalyze the initial steps of archaeal heme biosynthesis were recombinantly produced, purified, and their predicted enzymatic functions verified.

scholarly journals RidA Proteins Protect against Metabolic Damage by Reactive Intermediates

2020 ◽  
Vol 84 (3) ◽  
Author(s):  
Jessica L. Irons ◽  
Kelsey Hodge-Hanson ◽  
Diana M. Downs
Keyword(s):  
Sequence Homology ◽  
Protein Sequences ◽  
Reactive Intermediates ◽  
Reactive Intermediate ◽  
Free Living ◽  
Protein Superfamily ◽  
Link Type ◽  
Domains Of Life ◽  
Living Organisms

The Rid (YjgF/YER057c/UK114) protein superfamily was first defined by sequence homology with available protein sequences from bacteria, archaea, and eukaryotes (L. Parsons, N. Bonander, E. Eisenstein, M. Gilson, et al., Biochemistry 42:80–89, 2003, https://doi.org/10.1021/bi020541w). The archetypal subfamily, RidA (reactive intermediate deaminase A), is found in all domains of life, with the vast majority of free-living organisms carrying at least one RidA homolog.

scholarly journals Toxoplasma gondii requires its plant-like heme biosynthesis pathway for infection

2019 ◽  
Author(s):  
Amy Bergmann ◽  
Katherine Floyd ◽  
Melanie Key ◽  
Carly Dameron ◽  
Kerrick C. Rees ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
De Novo ◽  
Phylogenetic Analyses ◽  
Heme Biosynthesis ◽  
Microbial Pathogens ◽  
Biosynthesis Pathway ◽  
Prosthetic Group ◽  
Apicomplexan Parasites ◽  
Pathogenic Microbes ◽  
Living Organisms

Heme, an iron-enclosed organic ring, is essential for virtually all living organisms by serving as a prosthetic group in proteins that function in diverse cellular activities ranging from diatomic gas transport and detection to mitochondrial respiration to detoxification. Cellular heme levels in microbial pathogens can be a composite of endogenous de novo synthesis or exogenous uptake of heme or heme synthesis intermediates1,2. Intracellular pathogenic microbes switch routes for heme supply when heme availability in their replicative environment fluctuates through infections2. Here, we show that the Toxoplasma gondii, an obligate intracellular human pathogen, encodes a functional heme biosynthesis pathway. A chloroplast-derived organelle, termed apicoplast, is involved in the heme production. Genetic and chemical manipulation revealed that de novo heme production is essential for T. gondii intracellular growth and pathogenesis. Surprisingly, the herbicide oxadiazon significantly impaired Toxoplasma growth, consistent with phylogenetic analyses that show T. gondii protoporphyrinogen oxidase is more closely related to plants than mammals. We further improve upon this inhibition by 15-to 25-fold with two oxadiazon derivatives, providing therapeutic proof that Toxoplasma heme biosynthesis is a druggable target. As T. gondii has been used to model other apicomplexan parasites3, our study underscores the utility of targeting heme biosynthesis in other pathogenic apicomplexans.

scholarly journals Transcriptome analysis reveals candidate genes involved in luciferin metabolism inLuciola aquatilis(Coleoptera: Lampyridae)

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2534 ◽  
Author(s):  
Wanwipa Vongsangnak ◽  
Pramote Chumnanpuen ◽  
Ajaraporn Sriboonlert
Keyword(s):  
Candidate Genes ◽  
Transcriptome Analysis ◽  
Biosynthetic Pathway ◽  
De Novo ◽  
Rt Pcr ◽  
Reverse Transcription Pcr ◽  
Key Enzyme ◽  
Coleopteran Insect ◽  
Living Organisms ◽  
Pathway Databases

Bioluminescence, which living organisms such as fireflies emit light, has been studied extensively for over half a century. This intriguing reaction, having its origins in nature where glowing insects can signal things such as attraction or defense, is now widely used in biotechnology with applications of bioluminescence and chemiluminescence. Luciferase, a key enzyme in this reaction, has been well characterized; however, the enzymes involved in the biosynthetic pathway of its substrate, luciferin, remains unsolved at present. To elucidate the luciferin metabolism, we performed ade novotranscriptome analysis using larvae of the firefly species,Luciola aquatilis. Here, a comparative analysis is performed with the model coleopteran insectTribolium casteneumto elucidate the metabolic pathways inL. aquatilis. Based on a template luciferin biosynthetic pathway, combined with a range of protein and pathway databases, and various prediction tools for functional annotation, the candidate genes, enzymes, and biochemical reactions involved in luciferin metabolism are proposed forL. aquatilis. The candidate gene expression is validated in the adultL. aquatilisusing reverse transcription PCR (RT-PCR). This study provides useful information on the bio-production of luciferin in the firefly and will benefit to future applications of the valuable firefly bioluminescence system.

scholarly journals Metabolic Reconstruction Elucidates the Lifestyle of the Last Diplomonadida Common Ancestor

mSystems ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e00774-20
Author(s):  
Alejandro Jiménez-González ◽  
Jan O. Andersson
Keyword(s):  
Metabolic Networks ◽  
Common Ancestor ◽  
De Novo ◽  
Metabolic Reconstruction ◽  
Free Living ◽  
Content Type ◽  
Constant Change ◽  
Living Organisms ◽  
Close Relatives ◽  
Adaptation Processes

ABSTRACTThe identification of ancestral traits is essential to understanding the evolution of any group. In the case of parasitic groups, this helps us understand the adaptation to this lifestyle and a particular host. Most diplomonads are parasites, but there are free-living members of the group nested among the host-associated diplomonads. Furthermore, most of the close relatives within Fornicata are free-living organisms. This leaves the lifestyle of the ancestor unclear. Here, we present metabolic maps of four different diplomonad species. We identified 853 metabolic reactions and 147 pathways present in at least one of the analyzed diplomonads. Our study suggests that diplomonads represent a metabolically diverse group in which differences correlate with different environments (e.g., the detoxification of arsenic). Using a parsimonious analysis, we also provide a description of the putative metabolism of the last Diplomonadida common ancestor. Our results show that the acquisition and loss of reactions have shaped metabolism since this common ancestor. There is a net loss of reaction in all branches leading to parasitic diplomonads, suggesting an ongoing reduction in the metabolic capacity. Important traits present in host-associated diplomonads (e.g., virulence factors and the synthesis of UDP-N-acetyl-d-galactosamine) are shared with free-living relatives. The last Diplomonadida common ancestor most likely already had acquired important enzymes for the salvage of nucleotides and had a reduced capacity to synthesize nucleotides, lipids, and amino acids de novo, suggesting that it was an obligate host-associated organism.IMPORTANCE Diplomonads are a group of microbial eukaryotes found in oxygen-poor environments. There are both parasitic (e.g., Giardia intestinalis) and free-living (e.g., Trepomonas) members in the group. Diplomonads are well known for their anaerobic metabolism, which has been studied for many years. Here, we reconstructed whole metabolic networks of four extant diplomonad species as well as their ancestors, using a bioinformatics approach. We show that the metabolism within the group is under constant change throughout evolutionary time, in response to the environments that the different lineages explore. Both gene losses and gains are responsible for the adaptation processes. Interestingly, it appears that the last Diplomonadida common ancestor had a metabolism that is more similar to extant parasitic than free-living diplomonads. This suggests that the host-associated lifestyle of parasitic diplomonads, such as the human parasite G. intestinalis, is an old evolutionary adaptation.

scholarly journals A single regulator NrtR controls bacterial NAD+ homeostasis via its acetylation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rongsui Gao ◽  
Wenhui Wei ◽  
Bachar H Hassan ◽  
Jun Li ◽  
Jiaoyu Deng ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
De Novo ◽  
Common Mechanism ◽  
Acetyl Phosphate ◽  
Post Translational Modification ◽  
Positive Bacterium ◽  
Nad Metabolism ◽  
Domains Of Life

Nicotinamide adenine dinucleotide (NAD+) is an indispensable cofactor in all domains of life, and its homeostasis must be regulated tightly. Here we report that a Nudix-related transcriptional factor, designated MsNrtR (MSMEG_3198), controls the de novo pathway of NAD+biosynthesis in M. smegmatis, a non-tuberculosis Mycobacterium. The integrated evidence in vitro and in vivo confirms that MsNrtR is an auto-repressor, which negatively controls the de novo NAD+biosynthetic pathway. Binding of MsNrtR cognate DNA is finely mapped, and can be disrupted by an ADP-ribose intermediate. Unexpectedly, we discover that the acetylation of MsNrtR at Lysine 134 participates in the homeostasis of intra-cellular NAD+ level in M. smegmatis. Furthermore, we demonstrate that NrtR acetylation proceeds via the non-enzymatic acetyl-phosphate (AcP) route rather than by the enzymatic Pat/CobB pathway. In addition, the acetylation also occurs on the paralogs of NrtR in the Gram-positive bacterium Streptococcus and the Gram-negative bacterium Vibrio, suggesting that these proteins have a common mechanism of post-translational modification in the context of NAD+ homeostasis. Together, these findings provide a first paradigm for the recruitment of acetylated NrtR to regulate bacterial central NAD+ metabolism.

Prospective enzymes for omega-3 PUFA biosynthesis found in endoparasitic classes within the phylum Platyhelminthes

2020 ◽  
Vol 94 ◽  
Author(s):  
D. Babaran ◽  
M.T. Arts ◽  
R.J. Botelho ◽  
S.A. Locke ◽  
J. Koprivnikar
Keyword(s):  
Parasite Species ◽  
De Novo ◽  
Genomic Data ◽  
Wide Distribution ◽  
Omega 3 ◽  
Free Living ◽  
Chain Pufa ◽  
Pufa Biosynthesis ◽  
Aquatic Food ◽  
Long Chain

Abstract The free-living infectious stages of macroparasites, specifically, the cercariae of trematodes (flatworms), are likely to be significant (albeit underappreciated) vectors of nutritionally important polyunsaturated fatty acids (PUFA) to consumers within aquatic food webs, and other macroparasites could serve similar roles. In the context of de novo omega-3 (n-3) PUFA biosynthesis, it was thought that most animals lack the fatty acid (FA) desaturase enzymes that convert stearic acid (18:0) into ɑ-linolenic acid (ALA; 18:3n-3), the main FA precursor for n-3 long-chain PUFA. Recently, novel sequences of these enzymes were recovered from 80 species from six invertebrate phyla, with experimental confirmation of gene function in five phyla. Given this wide distribution, and the unusual attributes of flatworm genomes, we conducted an additional search for genes for de novo n-3 PUFA in the phylum Platyhelminthes. Searches with experimentally confirmed sequences from Rotifera recovered nine relevant FA desaturase sequences from eight species in four genera in the two exclusively endoparasite classes (Trematoda and Cestoda). These results could indicate adaptations of these particular parasite species, or may reflect the uneven taxonomic coverage of sequence databases. Although additional genomic data and, particularly, experimental study of gene functionality are important future validation steps, our results indicate endoparasitic platyhelminths may have enzymes for de novo n-3 PUFA biosynthesis, thereby contributing to global PUFA production, but also representing a potential target for clinical antihelmintic applications.

scholarly journals Natural variation in yolk fatty acids, but not androgens, predicts offspring fitness in a wild bird

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lucia Mentesana ◽  
Martin N. Andersson ◽  
Stefania Casagrande ◽  
Wolfgang Goymann ◽  
Caroline Isaksson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Maternal Effects ◽  
Natural Variation ◽  
De Novo ◽  
Natural Populations ◽  
Egg Laying ◽  
Interactive Effects ◽  
Free Living ◽  
Offspring Fitness

Abstract Background In egg-laying animals, mothers can influence the developmental environment and thus the phenotype of their offspring by secreting various substances into the egg yolk. In birds, recent studies have demonstrated that different yolk substances can interactively affect offspring phenotype, but the implications of such effects for offspring fitness and phenotype in natural populations have remained unclear. We measured natural variation in the content of 31 yolk components known to shape offspring phenotypes including steroid hormones, antioxidants and fatty acids in eggs of free-living great tits (Parus major) during two breeding seasons. We tested for relationships between yolk component groupings and offspring fitness and phenotypes. Results Variation in hatchling and fledgling numbers was primarily explained by yolk fatty acids (including saturated, mono- and polyunsaturated fatty acids) - but not by androgen hormones and carotenoids, components previously considered to be major determinants of offspring phenotype. Fatty acids were also better predictors of variation in nestling oxidative status and size than androgens and carotenoids. Conclusions Our results suggest that fatty acids are important yolk substances that contribute to shaping offspring fitness and phenotype in free-living populations. Since polyunsaturated fatty acids cannot be produced de novo by the mother, but have to be obtained from the diet, these findings highlight potential mechanisms (e.g., weather, habitat quality, foraging ability) through which environmental variation may shape maternal effects and consequences for offspring. Our study represents an important first step towards unraveling interactive effects of multiple yolk substances on offspring fitness and phenotypes in free-living populations. It provides the basis for future experiments that will establish the pathways by which yolk components, singly and/or interactively, mediate maternal effects in natural populations.

scholarly journals Biology of Heme in Mammalian Erythroid Cells and Related Disorders

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tohru Fujiwara ◽  
Hideo Harigae
Keyword(s):  
Biosynthetic Pathway ◽  
Iron Acquisition ◽  
Protoporphyrin Ix ◽  
Erythroid Differentiation ◽  
Heme Biosynthesis ◽  
Erythroid Cells ◽  
Prosthetic Group ◽  
Expression Of Genes ◽  
Human Disorders ◽  
Pathway Regulation

Heme is a prosthetic group comprising ferrous iron (Fe2+) and protoporphyrin IX and is an essential cofactor in various biological processes such as oxygen transport (hemoglobin) and storage (myoglobin) and electron transfer (respiratory cytochromes) in addition to its role as a structural component of hemoproteins. Heme biosynthesis is induced during erythroid differentiation and is coordinated with the expression of genes involved in globin formation and iron acquisition/transport. However, erythroid and nonerythroid cells exhibit distinct differences in the heme biosynthetic pathway regulation. Defects of heme biosynthesis in developing erythroblasts can have profound medical implications, as represented by sideroblastic anemia. This review will focus on the biology of heme in mammalian erythroid cells, including the heme biosynthetic pathway as well as the regulatory role of heme and human disorders that arise from defective heme synthesis.

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