The silent information regulator sirtuin 1 (SIRT1) protein is an NAD+-dependent class-III lysine deacetylase that serves as an important post-transcriptional modifier targeting lysine acetylation sites to mediate deacetylation modifications of histones and non-histone proteins. SIRT1 has been reported to be involved in several physiological or pathological processes such as aging, inflammation, immune responses, oxidative stress and allergic diseases. In this review, we summarized the regulatory roles of SIRT1 during allergic disorder progression. Furthermore, we highlight the therapeutic effects of targeting SIRT1 in allergic diseases.

Cryptococcus neoformans is a life-threatening fungal pathogen that is a causative agent for pulmonary infection and meningoencephalitis in both immunocompetent and immunodeficient individuals. Recent studies have elucidated the important function of the target of rapamycin (TOR) signaling pathway in the modulation of C. neoformans virulence factor production and pathogenicity in animal infection models. Herein, we discovered that Ypk1, a critical component of the TOR signaling pathway, acts as a critical modulator in fungal pathogenicity through post-translational modifications (PTMs). Mass spectrometry analysis revealed that Ypk1 is subject to protein acetylation at lysines 315 and 502, and both sites are located within kinase functional domains. Inhibition of the C. neoformans TOR pathway by rapamycin activates the deacetylation process for Ypk1. The YPK1Q strain, a hyper-acetylation of Ypk1, exhibited increased sensitivity to rapamycin, decreased capsule formation ability, reduced starvation tolerance, and diminished fungal pathogenicity, indicating that deacetylation of Ypk1 is crucial for responding to stress. Deacetylase inhibition assays have shown that sirtuin family proteins are critical to the Ypk1 deacetylation mechanism. After screening deacetylase mutants, we found that Dac1 and Dac7 directly interact with Ypk1 to facilitate the deacetylation modification process via a protein-protein interaction. These findings provide new insights into the molecular basis for regulating the TORC-Ypk1 axis and demonstrate an important function of protein acetylation in modulating fungal pathogenicity.
OBJECTIVE: Cryptococcus neoformans is an important opportunistic fungal pathogen in humans. While there are currently few effective antifungal treatments, the absence of novel molecular targets in fungal pathogenicity hinders the development of new drugs. There is increasing evidence that protein post-translational modifications (PTMs) can modulate the pathogenicity of fungi. In this study, we discovered that the pathogenicity of C. neoformans was significantly impacted by the dynamic acetylation changes of Ypk1, the immediate downstream target of the TOR complex. We discovered that Ypk1 is acetylated at lysines 315 and 502, both of which are within kinase functional domains. Deacetylation of Ypk1 is necessary for formation of the capsule structure, the response to the TOR pathway inhibitor rapamycin, nutrient utilization, and host infection. We also demonstrate that the sirtuin protein family is involved in the Ypk1 deacetylation mechanism. We anticipate that the sirtuin-Ypk1 regulation axis could be used as a potential target for the development of antifungal medications.

The silencing regulatory factor 2-like protein 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+) dependent deacetylase located primarily in the mitochondria. This protein plays an important role in oxidative stress, energy metabolism, and autophagy in multicellular organisms. Autophagy (macroautophagy) is primarily a cytoprotective mechanism necessary for intracellular homeostasis and the synthesis, degradation, and recycling of cellular products. Autophagy can influence the progression of several neural, cardiac, hepatic, and renal diseases and can also contribute to the development of fibrosis, diabetes, and many types of cancer. Recent studies have shown that SIRT3 has an important role in regulating autophagy. Therefore in this study, we aimed to perform a literature review to summarize the role of SIRT3 in the regulation of cellular autophagy. The findings of this study could be used to identify new drug targets for SIRT3-related diseases. Methods: A comprehensive literature review of the mechanism involved behind SIRT3 and autophagy-related diseases was performed. Relevant literature published in Pubmed and Web of Science up to July 2023 was identified using the keywords \"silencing regulatory factor 2-like protein 3\", \"SIRT3\" and \"autophagy\".

Lysine acetylation is an evolutionarily conserved and widespread post-translational modification implicated in the regulation of multiple metabolic processes, but its function remains largely unknown in plant pathogenic fungi. A comprehensive analysis combined with proteomic, molecular and cellular approaches was presented to explore the roles of cytoplasmic acetylation in Fusarium oxsysporum f.sp. lycopersici (Fol). The divergent cytoplasmic deacetylase FolSir2 was biochemically characterized, which is contributing to fungal virulence. Based on this, a total of 1752 acetylated sites in 897 proteins were identified in Fol via LC-MS/MS analysis. Further analyses of the quantitative acetylome revealed that 115 proteins representing two major pathways, translational and ribosome biogenesis, were hyperacetylated in the ∆Folsir2 strain. We experimentally examined the regulatory roles of FolSir2 on K271 deacetylation of FolGsk3, a serine/tyrosine kinase implicated in a variety of cellular functions, which was found to be crucial for the activation of FolGsk3 and thus modulated Fol pathogenicity. Cytoplasmic deacetylation by FolSir2 homologues has a similar function in Botrytis cinerea and likely other fungal pathogens. These findings reveal a conserved mechanism of silent information regulator 2-mediated cytoplasmic deacetylation that is involved in plant-fungal pathogenicity, providing a candidate target for designing broad-spectrum fungicides to control plant diseases.

OBJECTIVE: To investigate the possible role of La ribonucleoprotein 7 (LARP7) in psoriasis through a mouse model and uncover its underlying mechanism.
METHODS: The back skin of C57BL/6 mice was smeared with IMquimod (IMQ) cream for 7 days to induce psoriasis. Immunoblot kit was used to detect the deacetylase activity of SIRT1 (member of sirtuin family). Hematoxylin and eosin staining was used to assess the degree of psoriasis in mouse. Flow cytometry assays were performed to confirm effects on Th1/Th17 cell differentiation. Enzyme-linked-immunosorbent serologic assays were used to detect the level of secreted cytokines.
RESULTS: LARP7 upregulated SIRT1 deacetylase activity. LARP7 alleviated psoriasis symptoms in mice by upregulating SIRT1 deacetylase activity. In addition, LARP7 regulated Th1/Th17 cell differentiation in psoriatic mice. We further found that LARP7 inhibited Th1/Th17 cytokine.
CONCLUSIONS: LARP7 upregulated SIRT1 activity and inhibited Th1/Th17 cytokine response in psoriatic mice.

With potent herbicidal activity, biocatalysis synthesis of L-glufosinate has drawn attention. In present research, NAP-Das2.3, a deacetylase capable of stereoselectively resolving N-acetyl-L-glufosinate to L-glufosinate mined from Arenimonas malthae, was heterologously expressed and characterized. In Escherichia coli, NAP-Das2.3 activity only reached 0.25 U/L due to the formation of inclusive bodies. Efficient soluble expression of NAP-Das2.3 was achieved in Pichia pastoris. In shake flask and 5 L bioreactor fermentation, NAP-Das2.3 activity by recombinant P. pastoris reached 107.39 U/L and 1287.52 U/L, respectively. The optimum temperature and pH for N-acetyl-glufosinate hydrolysis by NAP-Das2.3 were 45 °C and pH 8.0, respectively. The Km and Vmax of NAP-Das2.3 towards N-acetyl-glufosinate were 25.32 mM and 19.23 μmol mg-1 min-1, respectively. Within 90 min, 92.71% of L-enantiomer in 100 mM racemic N-acetyl-glufosinate was converted by NAP-Das2.3. L-glufosinate with high optical purity (e.e.P above 99.9%) was obtained. Therefore, the recombinant NAP-Das2.3 might be an alternative for L-glufosinate biosynthesis.

Histone acetylation modification significantly affects secondary metabolism in filamentous fungi. However, how histone acetylation regulates secondary metabolite synthesis in the lovastatin (a lipid-lowering drug) producing Aspergillus terreus remains unknown because protein is involved and has been identified in this species. Here, the fungal-specific histone deacetylase gene, hstD, was characterized through functional genomics in two marine-derived A. terreus strains, Mj106 and RA2905. The results showed that the ablation of HstD resulted in reduced mycelium growth, less conidiation, and decreased lovastatin biosynthesis but significantly increased terrein biosynthesis. However, unlike its homologs in yeast, HstD was not required for fungal responses to DNA damage agents, indicating that HstD likely plays a novel role in the DNA damage repair process in A. terreus. Furthermore, the loss of HstD resulted in a significant upregulation of H3K56 and H3K27 acetylation when compared to the wild type, suggesting that epigenetic functions of HstD, as a deacetylase, target H3K27 and H3K56. Additionally, a set of no-histone targets with potential roles in fungal growth, conidiation, and secondary metabolism were identified for the first time using acetylated proteomic analysis. In conclusion, we provide a comprehensive analysis of HstD for its targets in histone or non-histone and its roles in fungal growth and development, DNA damage response, and secondary metabolism in A. terreus.

The Schizosaccharomyces pombe Clr6S complex, a class I histone deacetylase complex, functions as a zinc-dependent enzyme to remove acetyl groups from lysine residues in histone tails. We report here the cryo-EM structure of Clr6S alone and a cryo-EM map of Clr6S in complex with a nucleosome. The active center, revealed at near-atomic resolution, includes features important for catalysis-A water molecule coordinated by zinc, the likely nucleophile for attack on the acetyl-lysine bond, and a loop that may position the substrate for catalysis. The cryo-EM map in the presence of a nucleosome reveals multiple Clr6S-nucleosome contacts and a high degree of relative motion of Clr6S and the nucleosome. Such flexibility may be attributed to interaction at a site in the flexible histone tail and is likely important for the function of the deacetylase, which acts at multiple sites in other histone tails.

Deacetylases, a class of enzymes that can catalyze the hydrolysis of acetylated substrates to remove the acetyl group, used in producing various products with high qualities, are one of the most influential industrial enzymes. These enzymes are highly specific, non-toxic, sustainable, and eco-friendly biocatalysts. Deacetylases and deacetylated compounds have been widely applicated in pharmaceuticals, medicine, food, and the environment. This review synthetically summarizes deacetylases\' sources, characterizations, classifications, and applications. Moreover, the typical structural characteristics of deacetylases from different microbial sources are summarized. We also reviewed the deacetylase-catalyzed reactions for producing various deacetylated compounds, such as chitosan-oligosaccharide (COS), mycothiol, 7-aminocephalosporanic acid (7-ACA), glucosamines, amino acids, and polyamines. It is aimed to expound on the advantages and challenges of deacetylases in industrial applications. Moreover, it also serves perspectives on obtaining promising and innovative biocatalysts for enzymatic deacetylation. KEYPOINTS: • The fundamental properties of microbial deacetylases of various microorganisms are presented. • The biochemical characterizations, structures, and catalyzation mechanisms of microbial deacetylases are summarized. • The applications of microbial deacetylases in food, pharmaceutical, medicine, and the environment were discussed.

Upregulation of pyruvate kinase M2 (PKM2) is critical for the orchestration of metabolism and inflammation in critical illness, while autophagic degradation is a recently revealed mechanism that counter-regulates PKM2. Accumulating evidence suggests that sirtuin 1 (SIRT1) function as a crucial regulator in autophagy. The present study investigated whether SIRT1 activator would downregulate PKM2 in lethal endotoxemia via promotion of its autophagic degradation. The results indicated that lethal dose of lipopolysaccharide (LPS) exposure decreased the level of SIRT1. Treatment with SRT2104, a SIRT1 activator, reversed LPS-induced downregulation of LC3B-II and upregulation of p62, which was associated with reduced level of PKM2. Activation of autophagy by rapamycin also resulted in reduction of PKM2. The decline of PKM2 in SRT2104-treated mice was accompanied with compromised inflammatory response, alleviated lung injury, suppressed elevation of blood urea nitrogen (BUN) and brain natriuretic peptide (BNP), and improved survival of the experimental animals. In addition, co-administration of 3-methyladenine, an autophagy inhibitor, or Bafilomycin A1, a lysosome inhibitor, abolished the suppressive effects of SRT2104 on PKM2 abundance, inflammatory response and multiple organ injury. Therefore, promotion of autophagic degradation of PKM2 might be a novel mechanism underlying the anti-inflammatory benefits of SIRT1 activator.