Since the initial identification of cytochrome P450 monooxygenases (CYPs/P450s), great progress has been made in understanding their structure-function relationship, diversity and application in producing compounds beneficial to humans. However, the molecular evolution of P450s in terms of their dynamics both at protein and DNA levels and functional conservation across kingdoms still needs investigation. In this study, we analyzed 17 598 P450s belonging to 113 P450 families (bacteria −42; fungi −19; plant −28; animal −22; plant and animal −1 and common P450 family −1) and found highly conserved and rapidly evolving P450 families. Results suggested that bacterial P450s, particularly P450s belonging to mycobacteria, are highly conserved both at protein and DNA levels. Mycobacteria possess the highest P450 diversity percentage compared to other microbes and have a high coverage of P450s (≥1%) in their genomes, as found in fungi and plants. Phylogenetic and functional analyses revealed the functional conservation of P450s despite belonging to different biological kingdoms, suggesting the adherence of P450s to their innate function such as their involvement in either generation or oxidation of steroids and structurally related molecules, fatty acids and terpenoids. This study’s results offer new understanding of the dynamic structural nature of P450s.

Under extreme acidic environments, bacteria exploit several acid resistance (AR) mechanisms for enhancing their survival, which is concerned with several aspects, such as issues in human health and fermentation for acidic products. Currently, knowledge of bacterial AR mainly comes from the strong acid (such as hydrochloric acid) stresses, whereas AR mechanisms against organic weak acids (such as acetic acid), which are indeed encountered by bacteria, are less understood. Acetic acid bacteria (AAB), with the ability to produce acetic acid up to 20 g/100 mL, possess outstanding acetic acid tolerance, which is conferred by their unique AR mechanisms, including pyrroloquinoline quinine-dependent alcohol dehydrogenase, acetic acid assimilation and molecular chaperons. The distinguished AR of AAB toward acetic acid may provide a paradigm for research in bacterial AR against weak organic acids. In order to understand AAB’s AR mechanism more holistically, omics approaches have been employed in the corresponding field. However, the currently reported transcriptomic study was processed under a low-acidity (1 g/100 mL) environment, which could not reflect the general conditions that AAB are usually faced with. This study performed RNA-Seq transcriptomic analysis investigating AR mechanisms in Acetobacter pasteurianus CGMCC 1.41, a widely used vinegar-brewing AAB strain, at different stages of fermentation, namely, under different acetic acid concentrations (from 0.6 to 6.03 g/100 mL). The results demonstrated the even and clustered genomic distribution of up- and down-regulated genes, respectively. Difference in AR between AAB and other microorganisms was supported by the down-regulation of urea degradation and trehalose synthesis-related genes in response to acetic acid. Detailed analysis reflected the role of ethanol respiration as the main energy source and the limited effect of acetic acid assimilation on AR during fermentation as well as the competition between ethanol respiratory chain and NADH, succinate dehydrogenase-based common respiratory chain. Molecular chaperons contribute to AR, too, but their regulatory mechanisms require further investigation. Moreover, pathways of glucose catabolism and fatty acid biosynthesis are also related to AR. Finally, 2-methylcitrate cycle was proposed as an AR mechanism in AAB for the first time. This study provides new insight into AR mechanisms of AAB, and it also indicates the existence of numerous undiscovered AR mechanisms.

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Pancreatic β cell dysfunction contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic β cell function remains largely elusive. In the current study, we identify the pathway by which miR-21 regulates glucose-stimulated insulin secretion utilizing mice lacking miR-21 in their β cells (miR-21βKO). We find that miR-21βKO mice develop glucose intolerance due to impaired glucose-stimulated insulin secretion. Mechanistic studies reveal that miR-21 enhances glucose uptake and subsequently promotes insulin secretion by up-regulating Glut2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of Glut2 in knockout islets results in rescue of the impaired glucose-stimulated insulin secretion. Furthermore, we demonstrate that delivery of miR-21 into the pancreas of type 2 diabetic db/db male mice is able to promote Glut2 expression and reduce blood glucose level. Taking together, our results reveal that miR-21 in islet β cell promotes insulin secretion and support a role for miR-21 in the regulation of pancreatic β cell function in type 2 diabetes.