Subcellular Compartmentalization and Trafficking of the Biosynthetic Machinery for Fungal Melanin

Melanin is a complex multifunctional pigment found in all kingdoms of life, including fungi. The complex chemical structure of fungal melanins, yet to be fully elucidated, lends them multiple unique functions ranging from radioprotection and antioxidant activity to heavy metal chelation and organic compound absorption. Given their many biological functions, fungal melanins present many possibilities as natural compounds that could be exploited for human use. This review summarizes the current discourse and attempts to apply fungal melanin to enhance human health, remove pollutants from ecosystems, and streamline industrial processes. While the potential applications of fungal melanins are often discussed in the scientific community, they are successfully executed less often. Some of the challenges in the applications of fungal melanin to technology include the knowledge gap about their detailed structure, difficulties in isolating melanotic fungi, challenges in extracting melanin from isolated species, and the pathogenicity concerns that accompany working with live melanotic fungi. With proper acknowledgment of these challenges, fungal melanin holds great potential for societal benefit in the coming years.

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Stoichiometric Analysis of Shifting in Subcellular Compartmentalization of HSP70 within Ischemic Penumbra

Molecules ◽

10.3390/molecules26123578 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3578

Author(s):

Federica Mastroiacovo ◽

Francesca Biagioni ◽

Paola Lenzi ◽

Larisa Ryskalin ◽

Stefano Puglisi-Allegra ◽

...

Keyword(s):

Direct Evidence ◽

Neuronal Survival ◽

Hsp 70 ◽

Preclinical Models ◽

Brain Areas ◽

Cell Compartments ◽

Control Brain ◽

Disease Modifier ◽

Subcellular Compartmentalization

The heat shock protein (HSP) 70 is considered the main hallmark in preclinical studies to stain the peri-infarct region defined area penumbra in preclinical models of brain ischemia. This protein is also considered as a potential disease modifier, which may improve the outcome of ischemic damage. In fact, the molecule HSP70 acts as a chaperonine being able to impact at several level the homeostasis of neurons. Despite being used routinely to stain area penumbra in light microscopy, the subcellular placement of this protein within area penumbra neurons, to our knowledge, remains undefined. This is key mostly when considering studies aimed at deciphering the functional role of this protein as a determinant of neuronal survival. The general subcellular placement of HSP70 was grossly reported in studies using confocal microscopy, although no direct visualization of this molecule at electron microscopy was carried out. The present study aims to provide a direct evidence of HSP70 within various subcellular compartments. In detail, by using ultrastructural morphometry to quantify HSP70 stoichiometrically detected by immuno-gold within specific organelles we could compare the compartmentalization of the molecule within area penumbra compared with control brain areas. The study indicates that two cell compartments in control conditions own a high density of HSP70, cytosolic vacuoles and mitochondria. In these organelles, HSP70 is present in amount exceeding several-fold the presence in the cytosol. Remarkably, within area penumbra a loss of such a specific polarization is documented. This leads to the depletion of HSP70 from mitochondria and mostly cell vacuoles. Such an effect is expected to lead to significant variations in the ability of HSP70 to exert its physiological roles. The present findings, beyond defining the neuronal compartmentalization of HSP70 within area penumbra may lead to a better comprehension of its beneficial/detrimental role in promoting neuronal survival.

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Biosynthetic pathways and enzymes involved in the production of phosphonic acid natural products

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa052 ◽

2021 ◽

Vol 85 (1) ◽

pp. 42-52

Author(s):

Taro Shiraishi ◽

Tomohisa Kuzuyama

Keyword(s):

Natural Products ◽

Biosynthetic Pathway ◽

Organophosphorus Compounds ◽

Genome Mining ◽

Biological Molecules ◽

Antibacterial Drug ◽

Gene Encoding ◽

Quarter Century ◽

Lead Compounds ◽

Biosynthetic Machinery

Abstract Phosphonates are organophosphorus compounds possessing a characteristic C−P bond in which phosphorus is directly bonded to carbon. As phosphonates mimic the phosphates and carboxylates of biological molecules to potentially inhibit metabolic enzymes, they could be lead compounds for the development of a variety of drugs. Fosfomycin (FM) is a representative phosphonate natural product that is widely used as an antibacterial drug. Here, we review the biosynthesis of FM, which includes a recent breakthrough to find a missing link in the biosynthetic pathway that had been a mystery for a quarter-century. In addition, we describe the genome mining of phosphonate natural products using the biosynthetic gene encoding an enzyme that catalyzes C–P bond formation. We also introduce the chemoenzymatic synthesis of phosphonate derivatives. These studies expand the repertoires of phosphonates and the related biosynthetic machinery. This review mainly covers the years 2012-2020.

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Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis

Human Reproduction ◽

10.1093/humrep/dex365 ◽

2017 ◽

Vol 33 (2) ◽

pp. 258-269 ◽

Cited By ~ 14

Author(s):

Maria Gomes Fernandes ◽

Nannan He ◽

Fang Wang ◽

Liesbeth Van Iperen ◽

Cristina Eguizabal ◽

...

Keyword(s):

Germ Cell ◽

Cell Development ◽

P Element ◽

Germ Cell Development ◽

Subcellular Compartmentalization ◽

Human Specific

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Insights into the Functionality of the Putative Residues Involved in Enterocin AS-48 Maturation

Applied and Environmental Microbiology ◽

10.1128/aem.01154-10 ◽

2010 ◽

Vol 76 (21) ◽

pp. 7268-7276 ◽

Cited By ~ 19

Author(s):

Rubén Cebrián ◽

Mercedes Maqueda ◽

José Luis Neira ◽

Eva Valdivia ◽

Manuel Martínez-Bueno ◽

...

Keyword(s):

Posttranslational Modifications ◽

High Efficiency ◽

Specific Protein ◽

Culture Conditions ◽

Site Directed Mutagenesis ◽

Circular Structure ◽

Cleavage Enzyme ◽

Site Recognition ◽

Biosynthetic Machinery

ABSTRACT AS-48 is a 70-residue, α-helical, cationic bacteriocin produced by Enterococcus faecalis and is very singular in its circular structure and its broad antibacterial spectrum. The AS-48 preprotein consists of an N-terminal signal peptide (SP) (35 residues) followed by a proprotein moiety that undergoes posttranslational modifications to yield the mature and active circular protein. For the study of the specificity of the region of AS-48 that is responsible for maturation, three single mutants have been generated by site-directed mutagenesis in the as-48A structural gene. The substitutions were made just in the residues that are thought to constitute a recognition site for the SP cleavage enzyme (His-1, Met1) and in those involved in circularization (Met1, Trp70). Each derivative was expressed in the enterococcal JH2-2 strain containing the necessary native biosynthetic machinery for enterocin production. The importance of these derivatives in AS-48 processing has been evaluated on the basis of the production and structural characterization of the corresponding derivatives. Notably, only two of them (Trp70Ala and Met1Ala derivatives) could be purified in different forms and amounts and are characterized for their bactericidal activity and secondary structure. We could not detect any production of AS-48 in JH2-2(pAM401-81 His-1Ile ) by using the conventional chromatographic techniques, despite the high efficiency of the culture conditions applied to produce this enterocin. Our results underline the different important roles of the mutated residues in (i) the elimination of the SP, (ii) the production levels and antibacterial activity of the mature proteins, and (iii) protein circularization. Moreover, our findings suggest that His-1 is critically involved in cleavage site recognition, its substitution being responsible for the blockage of processing, thereby hampering the production of the specific protein in the cellular culture supernatant.

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Subcellular compartmentalization of myosin isoforms in embryonic chick heart ventricle myocytes during cytokinesis

Cell Motility and the Cytoskeleton ◽

10.1002/cm.970190307 ◽

1991 ◽

Vol 19 (3) ◽

pp. 189-206 ◽

Cited By ~ 25

Author(s):

Abigail H. Conrad ◽

William A. Clark ◽

Gary W. Conrad

Keyword(s):

Myosin Isoforms ◽

Embryonic Chick ◽

Heart Ventricle ◽

Chick Heart ◽

Embryonic Chick Heart ◽

Subcellular Compartmentalization

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Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases

Cells ◽

10.3390/cells10081990 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1990

Author(s):

Inmaculada Navarro-Lérida ◽

Miguel Sánchez-Álvarez ◽

Miguel Ángel del Pozo

Keyword(s):

Rho Gtpases ◽

Rho Gtpase ◽

Protein Complexes ◽

Specific Protein ◽

Cell Polarization ◽

Small Gtpase ◽

Post Translational Modification ◽

Functional Regulation ◽

Subcellular Compartmentalization ◽

Cellular Compartments

Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression—a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP–GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.

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Fungal melanins: a review

Canadian Journal of Microbiology ◽

10.1139/w98-119 ◽

1998 ◽

Vol 44 (12) ◽

pp. 1115-1136 ◽

Cited By ~ 386

Author(s):

M J Butler ◽

A W Day

Keyword(s):

Molecular Biology ◽

Analytical Methods ◽

Enzymatic Degradation ◽

Fundamental Properties ◽

Wide Range ◽

Lignin Peroxidases ◽

Fungal Melanin ◽

Relationship Of ◽

The Relationship ◽

Fungal Melanins

The relationship of polyketide melanogenesis molecular biology to that of nonmelanin-producing pathways in a wide range of fungi and other organisms is discussed. Analytical methods and fundamental properties of melanins are discussed and fungal melanin properties are compared with those of animal and bacterial melanins. The enzymatic degradation of melanins by lignin peroxidases is described.Key words: fungal melanin, polyketide melanin, DHN melanin, melanin degradation, melanin properties, melanin analysis.

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