Search

Latent tuberculosis, caused by dormant Mycobacterium tuberculosis (Mtb), poses a threat to global health through the incubation of undiagnosed infections within the community. Dormant Mtb, which is phenotypically tolerant to antibiotics, accumulates triacylglycerol (TAG) utilizing fatty acids obtained from macrophage lipid droplets. TAG is vital to mycobacteria, serving as a cell envelope component and energy reservoir during latency. TAG synthesis occurs by sequential acylation of glycerol‐3‐phosphate, wherein the second acylation step is catalyzed by acylglycerol‐3‐phosphate acyltransferase (AGPAT), resulting in the production of phosphatidic acid (PA), a precursor for the synthesis of TAG and various phospholipids. Here, we have characterized a putative acyltransferase of Mtb encoded by Rv3816c. We found that Rv3816c has all four characteristic motifs of AGPAT, exists as a membrane‐bound enzyme, and functions as 1‐acylglycerol‐3‐phosphate acyltransferase. The enzyme could transfer the acyl group to acylglycerol‐3‐phosphate (LPA) from monounsaturated fatty acyl‐coenzyme A of chain length 16 or 18 to produce PA. Complementation of Escherichia coli PlsC mutant in vivo by Rv3816c confirmed that it functions as AGPAT. Its active site mutants, H43A and D48A, were incapable of transferring the acyl group to LPA in vitro and were not able to rescue the growth defect of E. coli PlsC mutant in vivo. Identifying Rv3816c as AGPAT and comparing its properties with other AGPAT homologs is not only a step toward understanding the TAG biosynthesis in mycobacteria but has the potential to explore it as a drug target. [ABSTRACT FROM AUTHOR]

Mulberry leaf is a widely used protein feed and is often used as a strategy to reduce feed costs and improve meat quality in the livestock industry. However, to date, there is a lack of research on the improvement of meat quality using mulberry leaves, and the exact mechanisms are not yet known. The results showed that fermented mulberry leaves significantly reduced backfat content but had no significant effect on intramuscular fat (IMF). Lipidomic analysis showed that 98 and 303 differential lipid molecules (p < 0.05) were identified in adipose and muscle tissues, respectively, including triglycerides (TG), phosphatidylcholine, phosphatidylethanolamine, sphingolipids, and especially TG; therefore, we analysed the acyl carbon atom number of TG. The statistical results of acyl with different carbon atom numbers of TG in adipose tissue showed that the acyl group containing 13 carbon atoms (C13) in TG was significantly upregulated, whereas C15, C16, C17, and C23 were significantly downregulated, whereas in muscle tissue, the C12, C19, C23, C25, and C26 in TG were significantly downregulated. Acyl changes in TG were different for different numbers of carbon atoms in different tissues. We found that the correlations of C (14–18) in adipose tissue were higher, but in muscle tissue, the correlations of C (18–26) were higher. Through pathway enrichment analysis, we identified six and four metabolic pathways with the highest contributions of differential lipid metabolites in adipose and muscle tissues respectively. These findings suggest that fermented mulberry leaves improve meat quality mainly by inhibiting TG deposition by downregulating medium‐ and short‐chain fatty acids in backfat tissue and long‐chain fatty acids in muscle tissue. [ABSTRACT FROM AUTHOR]

The 2H‐tetrahydro‐4,6‐dioxo‐1,2‐oxazine (TDO) ring, a rare structural motif embedded in the molecular architecture of alchivemycins, is synthesized from 2,2,6‐trimethyl‐4H‐1,3‐dioxin‐4‐one via two routes. Both routes involve the intramolecular trapping of an acylketene intermediate by an internal hydroxy group to form the TDO ring as a key step. The first synthesis was achieved in 29 % overall yield from the starting material by a four‐step sequence featuring a DMAP−CaCl2‐mediated O‐ to C‐acyl migration reaction to install an acyl group at the C5 position of the TDO ring. The second synthesis was completed in 8 % overall yield from the same starting material as the first one through five steps by exploiting a photo‐induced double bromination reaction. [ABSTRACT FROM AUTHOR]

Since the discovery of the sirtuin family founding member (i.e., the yeast silent information regulator 2 (sir2) protein) in 2000, more and more sirtuin proteins have been identified and are currently known to be present in organisms from all the three kingdoms of life (i.e., bacteria, archaea, and eukarya). Seven sirtuin proteins have been identified in mammals including humans, that is, SIRT1/2/3/4/5/6/7. Sirtuin proteins are a class of enzymes with primary catalytic activity being the β‐nicotinamide adenine dinucleotide (β‐NAD+ or NAD+)‐dependent deacylation from the Nε‐acyl‐lysine residues on cellular proteins. Many sirtuins (e.g., human SIRT1/2/3/4/5/6/7) have been found to each possess multiple individual deacylase activities acting on Nε‐acyl‐lysine substrates with different acyl groups ranging from the simple formyl and acetyl to the more complex groups like succinyl and myristoyl; however, our current knowledge on the (patho)physiological roles of these individual deacylase activities is still limited, which could be due to the currently still thin research toolbox for investigation (i.e., the deacylase‐selective sirtuin mutant and inhibitor/activator). In this article, an updated account on the subject matter will be presented with biochemical and medicinal chemistry perspectives. [ABSTRACT FROM AUTHOR]

We developed intramolecular carboxyamidations of alkyne‐tethered O‐acylhydroxamates followed by either thermally induced spontaneous or 4‐(dimethylamino)pyridine‐catalyzed O→O or O→N acyl group migration. Under iron‐catalyzed conditions, the carboxyamidation products were generated in high yield from both Z‐alkene and arene‐tethered substrates. DFT calculations indicate that the iron‐catalyzed carboxyamidation proceeds via a stepwise mechanism involving iron‐imidyl radical cyclization followed by intramolecular acyloxy transfer from the iron center to the alkenyl radical center to furnish the cis‐carboxyamidation product. Upon treatment with 4‐(dimethylamino)pyridine, the Z‐alkene‐tethered carboxyamidation products underwent selective O→O acyl migration to generate 2‐acyloxy‐5‐acyl pyrroles. Thermal O→N acyl migration occurs during carboxyamidation if the Z‐alkene linker contains an alkyl or an aryl substituent at the β‐position of the carbonyl group. On the other hand, the arene linker‐containing compounds selectively undergo O→N acyl migration to generate N‐acyl‐3‐acylisoindolinones, and the corresponding O→O acyl migration forming isoindole derivatives was not observed. [ABSTRACT FROM AUTHOR]