Biomedical Applications of Lumazine Synthase

Wei, Yangjie; Kumar, Prashant; Wahome, Newton; Mantis, Nicholas J.; Middaugh, C. Russell

doi:10.1016/j.xphs.2018.05.002

Cited by 22 publications

(18 citation statements)

References 130 publications

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“…For a 3D structure modeled with PYRE2 in case of RibE [23] using published structures of RibH from B.subtilis and homologous RibE from E.coli, see Additional file 1: Figure S2 [24][25][26]. It has been considered as a drug target and may also have applications in biotechnology, vaccine carrier molecule development, and other fields due to its useful encapsulation abilities [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Transcription-dependent confined diffusion of enzymes within subcellular spaces of the bacterial cytoplasm

et al. 2021

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Background Knowledge on the localization and mobility of enzymes inside bacterial cells is scarce, but important for understanding spatial regulation of metabolism. The four central enzymes (Rib enzymes) of the riboflavin (RF) biosynthesis pathway in the Gram positive model bacterium Bacillus subtilis have been studied extensively in vitro, especially the heavy RF synthase, a large protein complex with a capsid structure formed by RibH and an encapsulated RibE homotrimer, which mediates substrate-channeling. However, little is known about the behavior and mobility of these enzymes in vivo. Results We have investigated the localization and diffusion of the Rib enzymes in the cytoplasm of B. subtilis. By characterizing the diffusion of Rib enzymes in live cells using single particle tracking (SPT) we provide evidence for confined diffusion at the cell poles and otherwise Brownian motion. A majority of RibH particles showed clear nucleoid occlusion and a high degree of confined motion, which is largely abolished after treatment with Rifampicin, revealing that confinement is dependent on active transcription. Contrarily, RibE is mostly diffusive within the cell, showing only 14% encapsulation by RibH nanocompartments. By localizing different diffusive populations within single cells, we find that fast diffusion occurs mostly across the nucleoids located in the cell centers, while the slower, confined subdiffusion occurs at the crowded cell poles. Conclusions Our results provide evidence for locally different motion of active enzymes within the bacterial cytoplasm, setting up metabolic compartmentalization mostly at the poles of cells.

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Section: Introductionmentioning

confidence: 99%

Transcription-dependent confined diffusion of enzymes within subcellular spaces of the bacterial cytoplasm

et al. 2021

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“…Lumazine synthase (LS), an enzyme involved in riboflavin biosynthesis, is distributed extensively in organisms, including archaea, eubacteria, bacteria, fungi, and plants. [112][113][114] With as many as 12 pentamers or more than 300 subunits, a number of porous shell-like structures have been reported, all of which were able to generate strong humoral and cellular immunity. [115,116] Foreign peptides or proteins inserted at its N-terminus do not disrupt general peptide folding, representing another example of a particulate base for the repetitive display of vaccine candidates.…”

Section: Lumazine Synthasementioning

confidence: 99%

Self‐Assembled Nanoparticles: Exciting Platforms for Vaccination

Pan

Cui

2020

Biotechnology Journal

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Vaccination is successfully advanced to control several fatal diseases and improve human life expectancy. However, additional innovations are required in this field because there are no effective vaccines to prevent some infectious diseases. The shift from the attenuated or inactivated pathogens to safer but less immunogenic protein or peptide antigens has led to a search for effective antigen delivery carriers that can function as both antigen vehicles and intrinsic adjuvants. Among these carriers, self-assembled nanoparticles (SANPs) have shown great potential to be the best representative. For the nanoscale and multiple presentation of antigens, with accurate control over size, geometry, and functionality, these nanoparticles are assembled spontaneously and mimic pathogens, resulting in enhanced antigen presentation and increased cellular and humoral immunity responses. In addition, they may be applied through needle-free routes due to their adhesive ability, which gives them a great future in vaccination applications. This review provides an overview of various SANPs and their applications in prophylactic vaccines.

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“…74 The enzymes lumazine synthase and riboflavin synthase have been studied extensively with the aim of developing antibiotic drugs from inhibitors of these enzymes. 74,75 8-Ribityl lumazines 58 and 59 were first isolated from the mycelium of the fungus Eremothecium ashbyii, along with riboflavin (55) in 1956. 76 The structure of lumazine 58 was assigned by comparing its spectroscopic data with that of the known 6,7,8-trimethyllumazine.…”

Section: Journal Of Natural Productsmentioning

confidence: 99%

“…A total synthesis of penilumamides B−D (72−74) was reported in 2017. 93 Aspergilumamide A (75), which contains a glutamine residue linked to the anthranilate group, was isolated from a mangrove-derived fungus Aspergillus sp., along with penilumamide A (71). 94 The biosynthetic pathway of these lumazine peptides (71−75) was proposed to start from lumazine-6-carboxylic acid (25), formed via folic acid catabolism, followed by stepwise addition of the amino acid (methionine or glutamine) and anthranilic acid.…”

Section: ■ Lumazine Peptidesmentioning

confidence: 99%