תפריט נגישות
ניגודיות עדינהניגודיות גבוהה
מונוכרום
הדגשת קישורים
חסימת אנימציה
פונט קריא
סגור
איפוס הגדרות נגישות
להורדת מודול נגישות חינם תפריט נגישותניגודיות עדינהניגודיות גבוההמונוכרוםהדגשת קישוריםחסימת אנימציהפונט קריאסגוראיפוס הגדרות נגישותלהורדת מודול נגישות חינםVijay K. Sharma
Ravindra Nath Kharwar
Microorganisms comprise a group of highly diverse life forms on the Earth. Microbes, including bacteria and fungi, produce a vast variety of natural products that are an unparalleled resource of industrial and pharmaceutical significance. Bacterial and fungal genome sequencing disclosed the presence of numerous secondary metabolites biosynthetic gene clusters (BGC). For example, analysis of next-generation sequencing data of Aspergillus spp. has revealed that a single strain has far more secondary metabolites BGCs that outnumber previously isolated natural products in the laboratory (Khaldi et al., 2010; Sanchez et al., 2012). These silent (cryptic) gene clusters harbor a treasure of novel bioactive metabolites for drug discovery. However, under standard laboratory conditions, only a portion of these compounds are accessible. Under normal conditions, some BGCs remain silent or expressed at low levels (Skellam, 2019; Wu et al., 2020). Gene expression can be triggered by changing cultivation parameters or applying physical, biological or chemical stresses (Scherlach and Hertweck, 2009). These silent genes could be activated by employing epigenetic manipulation approaches. Epigenetics describes the heritable changes in gene expression that occur without a change in the genome sequence. These epigenetic changes of the DNA strands are reversible, enabling adaptation and modulation of gene(s) expression in fluctuating environments.
In recent years, such epigenetic modulation has led to the discovery of several newly identified natural biomolecules. Epigenetic manipulations include gene knockouts that alter the expression and functionality of specific enzymes involved in creating and modulating DNA methylation patterns. Common molecular modifications that form the basis of epigenetic gene regulation include DNA methylation, chromatin remodeling, covalent histone modification, the localization of histone variants and feedback loops (Akone et al., 2019; Poças-Fonseca et al., 2020) (Figure 1). Consequently, DNA methyltransferase inhibitors and/or histone deacetylase inhibitors frequently target the genes knockout. Treatments of bacteria and fungi with DNA methyltransferase (DNMT) inhibitors like 5-azacytidine, procaine, procainamide, and hydralazine, and histone deacetylase (HDAC) inhibitors like sodium butyrate, suberoylanilide hydroxamic acid (SAHA) and valproic acid have been reported to induce the cryptic genes or activation of biosynthetic pathways of secondary metabolites. In addition to genetic modulation, a number of recent studies have suggested that various active food components present in dietary ingredients like turmeric, grapes, or green tea may also stimulate epigenetic changes (Sharma et al., 2017; Evans et al., 2020; Mishra et al., 2020). Pathogen-triggered epigenetic changes may also alter host cell functions, either to promote host defense or to favor pathogen persistence. Epigenetic mechanisms are known to repress and control expression of genes involved in pathogenicity (Tannous et al., 2020). Thus, epigenetic regulations have the potential application in controlling pathogenesis and post-harvest plant pathogens. Epigenetic perturbation of gene clusters leverages microorganisms for biosynthesizing new chemical entities of pharmaceutical and industrial importance. Further, epigenetic manipulations are also known to affect the metabolite pathways such as polyketide biosynthesis, induced production of cryptic compounds, restoration of attenuated compounds, and the production of host origin bioactive compounds.
Vijay K. Sharma
Ravindra Nath Kharwar
Microorganisms comprise a group of highly diverse life forms on the Earth. Microbes, including bacteria and fungi, produce a vast variety of natural products that are an unparalleled resource of industrial and pharmaceutical significance. Bacterial and fungal genome sequencing disclosed the presence of numerous secondary metabolites biosynthetic gene clusters (BGC). For example, analysis of next-generation sequencing data of Aspergillus spp. has revealed that a single strain has far more secondary metabolites BGCs that outnumber previously isolated natural products in the laboratory (Khaldi et al., 2010; Sanchez et al., 2012). These silent (cryptic) gene clusters harbor a treasure of novel bioactive metabolites for drug discovery. However, under standard laboratory conditions, only a portion of these compounds are accessible. Under normal conditions, some BGCs remain silent or expressed at low levels (Skellam, 2019; Wu et al., 2020). Gene expression can be triggered by changing cultivation parameters or applying physical, biological or chemical stresses (Scherlach and Hertweck, 2009). These silent genes could be activated by employing epigenetic manipulation approaches. Epigenetics describes the heritable changes in gene expression that occur without a change in the genome sequence. These epigenetic changes of the DNA strands are reversible, enabling adaptation and modulation of gene(s) expression in fluctuating environments.
In recent years, such epigenetic modulation has led to the discovery of several newly identified natural biomolecules. Epigenetic manipulations include gene knockouts that alter the expression and functionality of specific enzymes involved in creating and modulating DNA methylation patterns. Common molecular modifications that form the basis of epigenetic gene regulation include DNA methylation, chromatin remodeling, covalent histone modification, the localization of histone variants and feedback loops (Akone et al., 2019; Poças-Fonseca et al., 2020) (Figure 1). Consequently, DNA methyltransferase inhibitors and/or histone deacetylase inhibitors frequently target the genes knockout. Treatments of bacteria and fungi with DNA methyltransferase (DNMT) inhibitors like 5-azacytidine, procaine, procainamide, and hydralazine, and histone deacetylase (HDAC) inhibitors like sodium butyrate, suberoylanilide hydroxamic acid (SAHA) and valproic acid have been reported to induce the cryptic genes or activation of biosynthetic pathways of secondary metabolites. In addition to genetic modulation, a number of recent studies have suggested that various active food components present in dietary ingredients like turmeric, grapes, or green tea may also stimulate epigenetic changes (Sharma et al., 2017; Evans et al., 2020; Mishra et al., 2020). Pathogen-triggered epigenetic changes may also alter host cell functions, either to promote host defense or to favor pathogen persistence. Epigenetic mechanisms are known to repress and control expression of genes involved in pathogenicity (Tannous et al., 2020). Thus, epigenetic regulations have the potential application in controlling pathogenesis and post-harvest plant pathogens. Epigenetic perturbation of gene clusters leverages microorganisms for biosynthesizing new chemical entities of pharmaceutical and industrial importance. Further, epigenetic manipulations are also known to affect the metabolite pathways such as polyketide biosynthesis, induced production of cryptic compounds, restoration of attenuated compounds, and the production of host origin bioactive compounds.
