Origin and diversification of the cardiolipin biosynthetic pathway in the Eukarya domain

2020 ◽  
Vol 48 (3) ◽  
pp. 1035-1046
Author(s):  
Luis Alberto Luévano-Martínez ◽  
Anna L. Duncan
Keyword(s):  
Biosynthetic Pathway ◽  
Bacterial Enzymes ◽  
Bacterial Endosymbiont ◽  
Anionic Phospholipids ◽  
Cellular Processes ◽  
The Third ◽  
Domains Of Life ◽  
Cardiolipin Synthase ◽  
Hydrolase Family ◽  
Phosphate Synthase

Cardiolipin (CL) and its precursor phosphatidylglycerol (PG) are important anionic phospholipids widely distributed throughout all domains of life. They have key roles in several cellular processes by shaping membranes and modulating the activity of the proteins inserted into those membranes. They are synthesized by two main pathways, the so-called eukaryotic pathway, exclusively found in mitochondria, and the prokaryotic pathway, present in most bacteria and archaea. In the prokaryotic pathway, the first and the third reactions are catalyzed by phosphatidylglycerol phosphate synthase (Pgps) belonging to the transferase family and cardiolipin synthase (Cls) belonging to the hydrolase family, while in the eukaryotic pathway, those same reactions are catalyzed by unrelated homonymous enzymes: Pgps of the hydrolase family and Cls of the transferase family. Because of the enzymatic arrangement found in both pathways, it seems that the eukaryotic pathway evolved by convergence to the prokaryotic pathway. However, since mitochondria evolved from a bacterial endosymbiont, it would suggest that the eukaryotic pathway arose from the prokaryotic pathway. In this review, it is proposed that the eukaryote pathway evolved directly from a prokaryotic pathway by the neofunctionalization of the bacterial enzymes. Moreover, after the eukaryotic radiation, this pathway was reshaped by horizontal gene transfers or subsequent endosymbiotic processes.

scholarly journals The Hexosamine Biosynthetic Pathway as a Therapeutic Target after Cartilage Trauma: Modification of Chondrocyte Survival and Metabolism by Glucosamine Derivatives and PUGNAc in an Ex Vivo Model

2021 ◽  
Vol 22 (14) ◽  
pp. 7247
Author(s):  
Jana Riegger ◽  
Julia Baumert ◽  
Frank Zaucke ◽  
Rolf E. Brenner
Keyword(s):  
Biosynthetic Pathway ◽  
Ex Vivo ◽  
Type Ii Collagen ◽  
Cartilage Explants ◽  
Uridine Diphosphate ◽  
Cell Protection ◽  
Ex Vivo Model ◽  
Human Cartilage ◽  
Hexosamine Biosynthetic Pathway ◽  
Cellular Processes

The hexosamine biosynthetic pathway (HBP) is essential for the production of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the building block of glycosaminoglycans, thus playing a crucial role in cartilage anabolism. Although O-GlcNAcylation represents a protective regulatory mechanism in cellular processes, it has been associated with degenerative diseases, including osteoarthritis (OA). The present study focuses on HBP-related processes as potential therapeutic targets after cartilage trauma. Human cartilage explants were traumatized and treated with GlcNAc or glucosamine sulfate (GS); PUGNAc, an inhibitor of O-GlcNAcase; or azaserine (AZA), an inhibitor of GFAT-1. After 7 days, cell viability and gene expression analysis of anabolic and catabolic markers, as well as HBP-related enzymes, were performed. Moreover, expression of catabolic enzymes and type II collagen (COL2) biosynthesis were determined. Proteoglycan content was assessed after 14 days. Cartilage trauma led to a dysbalanced expression of different HBP-related enzymes, comparable to the situation in highly degenerated tissue. While GlcNAc and PUGNAc resulted in significant cell protection after trauma, only PUGNAc increased COL2 biosynthesis. Moreover, PUGNAc and both glucosamine derivatives had anti-catabolic effects. In contrast, AZA increased catabolic processes. Overall, “fueling” the HBP by means of glucosamine derivatives or inhibition of deglycosylation turned out as cells and chondroprotectives after cartilage trauma.

The malS-5′UTR regulates hisG, a key gene in the histidine biosynthetic pathway in Salmonella enterica serovar Typhi

2017 ◽  
Vol 63 (4) ◽  
pp. 287-295 ◽  
Author(s):  
Ying Zhang ◽  
Dongmei Yan ◽  
Lin Xia ◽  
Xin Zhao ◽  
George Osei-Adjei ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Rna Structure ◽  
Biosynthetic Pathway ◽  
Salmonella Typhi ◽  
Base Pairing ◽  
Salmonella Enterica Serovar Typhi ◽  
Cellular Processes ◽  
Invasive Capacity ◽  
Shine Dalgarno Sequence ◽  
Bax Gene

Bacterial noncoding RNAs (ncRNA) regulate diverse cellular processes, including virulence and environmental fitness. The malS 5′ untranslated region (named malS-5′UTR) was identified as a regulatory ncRNA that increases the invasive capacity of Salmonella enterica serovar Typhi. An IntaRNA search suggested base pairing between malS-5′UTR and hisG mRNA, a key gene in the histidine biosynthetic pathway. Overexpression of malS-5′UTR markedly reduced bacterial growth in minimal medium without histidine. Overexpression of malS-5′UTR increased mRNA from his operon genes, independently of the bax gene, and decreased HisG protein in Salmonella Typhi. RNA structure analysis showed base pairing of the malS-5′UTR RNA with the hisG mRNA across the ribosome binding site. Thus, we propose that malS-5′UTR inhibited hisG translation, probably by base pairing to the Shine–Dalgarno sequence.

scholarly journals Expression, Purification, and Characterization of (R)-Sulfolactate Dehydrogenase (ComC) from the Rumen MethanogenMethanobrevibacter milleraeSM9

Archaea ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Yanli Zhang ◽  
Linley R. Schofield ◽  
Carrie Sang ◽  
Debjit Dey ◽  
Ron S. Ronimus
Keyword(s):  
Biosynthetic Pathway ◽  
Critical Role ◽  
Reduction Reaction ◽  
Coenzyme M ◽  
Purification And Characterization ◽  
The Third ◽  
Optimal Activity ◽  
Methyl Coenzyme M Reductase

(R)-Sulfolactate dehydrogenase (EC 1.1.1.337), termed ComC, is a member of an NADH/NADPH-dependent oxidoreductase family of enzymes that catalyze the interconversion of 2-hydroxyacids into their corresponding 2-oxoacids. The ComC reaction is reversible and in the biosynthetic direction causes the conversion of (R)-sulfolactate to sulfopyruvate in the production of coenzyme M (2-mercaptoethanesulfonic acid). Coenzyme M is an essential cofactor required for the production of methane by the methyl-coenzyme M reductase complex. ComC catalyzes the third step in the first established biosynthetic pathway of coenzyme M and is also involved in methanopterin biosynthesis. In this study, ComC fromMethanobrevibacter milleraeSM9 was cloned and expressed inEscherichia coliand biochemically characterized. Sulfopyruvate was the preferred substrate using the reduction reaction, with 31% activity seen for oxaloacetate and 0.2% seen forα-ketoglutarate. Optimal activity was observed at pH 6.5. The apparentKMfor coenzyme (NADH) was 55.1 μM, and for sulfopyruvate, it was 196 μM (for sulfopyruvate theVmaxwas 93.9 μmol min−1 mg−1andkcatwas 62.8 s−1). The critical role of ComC in two separate cofactor pathways makes this enzyme a potential means of developing methanogen-specific inhibitors for controlling ruminant methane emissions which are increasingly being recognized as contributing to climate change.

scholarly journals Sirtuin-dependent reversible lysine acetylation of glutamine synthetases reveals an autofeedback loop in nitrogen metabolism

2016 ◽  
Vol 113 (24) ◽  
pp. 6653-6658 ◽  
Author(s):  
Di You ◽  
Bin-Cheng Yin ◽  
Zhi-Hai Li ◽  
Ying Zhou ◽  
Wen-Bang Yu ◽  
...  
Keyword(s):  
Nitrogen Metabolism ◽  
Feedback Regulation ◽  
Nutrient Sensing ◽  
Saccharopolyspora Erythraea ◽  
Regulatory Function ◽  
Lysine Acetylation ◽  
Cellular Processes ◽  
Domains Of Life ◽  
Lysine Acetyltransferase ◽  
Response To Environmental Change

In cells of all domains of life, reversible lysine acetylation modulates the function of proteins involved in central cellular processes such as metabolism. In this study, we demonstrate that the nitrogen regulator GlnR of the actinomycete Saccharopolyspora erythraea directly regulates transcription of the acuA gene (SACE_5148), which encodes a Gcn5-type lysine acetyltransferase. We found that AcuA acetylates two glutamine synthetases (GlnA1 and GlnA4) and that this lysine acetylation inactivated GlnA4 (GSII) but had no significant effect on GlnA1 (GSI-β) activity under the conditions tested. Instead, acetylation of GlnA1 led to a gain-of-function that modulated its interaction with the GlnR regulator and enhanced GlnR–DNA binding. It was observed that this regulatory function of acetylated GSI-β enzymes is highly conserved across actinomycetes. In turn, GlnR controls the catalytic and regulatory activities (intracellular acetylation levels) of glutamine synthetases at the transcriptional and posttranslational levels, indicating an autofeedback loop that regulates nitrogen metabolism in response to environmental change. Thus, this GlnR-mediated acetylation pathway provides a signaling cascade that acts from nutrient sensing to acetylation of proteins to feedback regulation. This work presents significant new insights at the molecular level into the mechanisms underlying the regulation of protein acetylation and nitrogen metabolism in actinomycetes.

scholarly journals Bioinformatics of Metalloproteins and Metalloproteomes

Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3366
Author(s):  
Yan Zhang ◽  
Junge Zheng
Keyword(s):  
Comparative Genomics ◽  
Metal Binding ◽  
Computational Prediction ◽  
Bioinformatic Analysis ◽  
Research Progress ◽  
Evolutionary Patterns ◽  
Cellular Processes ◽  
Metal Binding Sites ◽  
Domains Of Life ◽  
Systematic Understanding

Trace metals are inorganic elements that are required for all organisms in very low quantities. They serve as cofactors and activators of metalloproteins involved in a variety of key cellular processes. While substantial effort has been made in experimental characterization of metalloproteins and their functions, the application of bioinformatics in the research of metalloproteins and metalloproteomes is still limited. In the last few years, computational prediction and comparative genomics of metalloprotein genes have arisen, which provide significant insights into their distribution, function, and evolution in nature. This review aims to offer an overview of recent advances in bioinformatic analysis of metalloproteins, mainly focusing on metalloprotein prediction and the use of different metals across the tree of life. We describe current computational approaches for the identification of metalloprotein genes and metal-binding sites/patterns in proteins, and then introduce a set of related databases. Furthermore, we discuss the latest research progress in comparative genomics of several important metals in both prokaryotes and eukaryotes, which demonstrates divergent and dynamic evolutionary patterns of different metalloprotein families and metalloproteomes. Overall, bioinformatic studies of metalloproteins provide a foundation for systematic understanding of trace metal utilization in all three domains of life.

scholarly journals Subcellular localization and tissue distribution of sialic acid-forming enzymes. N-acetylneuraminate-9-phosphate synthase and N-acetylneuraminate 9-phosphatase

1984 ◽  
Vol 223 (2) ◽  
pp. 323-328 ◽  
Author(s):  
J Van Rinsum ◽  
W Van Dijk ◽  
G J Hooghwinkel ◽  
W Ferwerda
Keyword(s):  
Subcellular Localization ◽  
Biosynthetic Pathway ◽  
Cytosolic Fraction ◽  
Phosphate Esters ◽  
Rat Tissues ◽  
Acetylneuraminic Acid ◽  
Nitrophenyl Phosphate ◽  
Sucrose Medium ◽  
Hydrolysis Of ◽  
Phosphate Synthase

The activities of N-acetylneuraminate 9-phosphate synthase and N-acetylneuraminate 9-phosphatase, the two enzymes involved in the final steps of the biosynthetic pathway of N-acetylneuraminic acid, were measured with the substrates N-acetyl[14C]mannosamine 6-phosphate and N-acetyl[14C]neuraminic acid 9-phosphate respectively. Subcellular localization studies in rat liver indicated that both enzymes are localized in the cytosolic fraction after homogenization in sucrose medium. To test the possibility of misinterpretation due to the hydrolysis of N-acetylneuraminic acid 9-phosphate by non-specific phosphatases, the hydrolysis of various phosphate esters by the cytosolic fraction was tested. Only p-nitrophenyl phosphate was hydrolysed; however, competition studies with N-acetylneuraminic acid 9-phosphate and p-nitrophenyl phosphate indicated that two different enzymes were involved and that no competition existed between the two substrates. In various other rat tissues N-acetylneuraminate-9-phosphate synthase and N-acetylneuraminate 9-phosphatase activities were detected, suggesting that N-acetylmannosamine 6-phosphate is a general precursor for N-acetylneuraminic acid biosynthesis in all the tissues studied.

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.

The Role of Bacterial Enzymes in Inducing Inflammation in the Middle Ear Cavity

1979 ◽  
Vol 87 (6) ◽  
pp. 859-870 ◽  
Author(s):  
Seth H. Lowell ◽  
S. K. Juhn
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Bacterial Infections ◽  
Current Knowledge ◽  
Acute Otitis Media ◽  
Bacterial Enzymes ◽  
Infectious Process ◽  
The Third ◽  
Host Tissues

Current knowledge of the pathophysiology of bacterial infections is elementary. The initial events leading to the invasion of host tissues are a matter of conjecture for many bacterial organisms. This is particularly true for pneumococci, the most frequent causative organisms of acute otitis media. Bacterial enzymes may account for the initial disruption of host tissues, and this study explored their role in the infectious process. As a first step, pneumococcal cultures were analyzed, and significant levels of the enzymes lipase and hyaluronidase were demonstrated. Secondly, the presence of these enzymes in middle ear effusions was explored in an animal model of acute otitis media. The enzymes reached peak levels at seven days. The third and most important portion of the study examined the significance of these enzymes in producing inflammation and alterations in the middle ear cavity of normal experimental animals. This portion was a histologic comparison of temporal bone specimens and demonstrated that marked acute and chronic changes can be induced by placing solutions of these enzymes in the middle ear cavity. This study concludes that bacterial enzymes play an important role in the induction of acute otitis media.

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