[Microbial production of S-adenosyl-l-methionine: a review].

S-adenosyl-l-methionine (SAM) is ubiquitous in living organisms and plays important roles in transmethylation, transsulfuration and transamination in organisms. Due to its important physiological functions, production of SAM has attracted increasing attentions. Currently, researches on SAM production mainly focus on microbial fermentation, which is more cost-effective than that of the chemical synthesis and the enzyme catalysis, thus easier to achieve commercial production. With the rapid growth in SAM demand, interests in improving SAM production by developing SAM hyper-producing microorganisms aroused. The main strategies for improving SAM productivity of microorganisms include conventional breeding and metabolic engineering. This review summarizes the recent research progress in improving microbial SAM productivity to facilitate further improving SAM productivity. The bottlenecks in SAM biosynthesis and the solutions were also addressed.

Improvement of S-adenosyl-L-methionine production in Saccharomyces cerevisiae by atmospheric and room temperature plasma-ultraviolet compound mutagenesis and droplet microfluidic adaptive evolution.

To improve S-Adenosyl-L-methionine (a compound with important physiological functions, SAM) production, atmospheric and room temperature plasma and ultraviolet-LiCl mutagenesis were carried out with Saccharomyces cerevisiae strain ZY 1-5. The mutants were screened with ethionine, L-methionine, nystatin and cordycepin as screening agents. Adaptive evolution of a positive mutant UV6-69 was further performed by droplet microfluidics cultivation with ethionine as screening pressure. After adaptation, mutant T11-1 was obtained. Its SAM titer in shake flask fermentation reached 1.31 g/L, which was 191% higher than that of strain ZY 1-5. Under optimal conditions, the SAM titer and biomass of mutant T11-1 in 5 L bioreactor reached 10.72 g/L and 105.9 g dcw/L (142.86% and 34.22% higher than those of strain ZY 1-5), respectively. Comparative transcriptome analysis between strain ZY 1-5 and mutant T11-1 revealed the enhancements in TCA cycle and gluconeogenesis/glycolysis pathways as well as the inhibitions in serine and ergosterol synthesis of mutant T11-1. The elevated SAM synthesis of mutant T11-1 may attribute to the above changes. Taken together, this study is helpful for industrial production of SAM.

Gene Cascade Shift and Pathway Enrichment in Rat Kidney Induced by Acarbose Through Comparative Analysis.

Acarbose is an effective anti-diabetic drug to treat type 2 diabetes mellitus (T2DM), a chronic degenerative metabolic disease caused by insulin resistance. The beneficial effects of acarbose on blood sugar control in T2DM patients have been confirmed by many studies. However, the effect of acarbose on patient kidney has yet to be fully elucidated. In this study, we report in detail the gene expression cascade shift, pathway and module enrichment, and interrelation network in acarbose-treated Rattus norvegicus kidneys based on the in-depth analysis of the GSE59913 microarray dataset. The significantly differentially expressed genes (DEGs) in the kidneys of acarbose-treated rats were initially screened out by comparative analysis. The enriched pathways for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were further identified. The protein-protein interaction (PPI) analysis for DEGs was achieved through the STRING database mining. Pathway interrelation and hub genes for enriched pathways were further examined to uncover key biological effects of acarbose. Results revealed 44 significantly up-regulated genes and 86 significantly down-regulated genes (130 significant differential genes in total) in acarbose-treated rat kidneys. Lipid metabolism pathways were considerably improved by acarbose, and the physical conditions in chronic kidney disease (CKD) patients were improved possibly through the increase of the level of high-density lipoprotein (HDL) by lecithin-cholesterol acyl-transferase (LCAT). These findings suggested that acarbose may serve as an ideal drug for CKD patients, since it not only protects the kidney, but also may relieve the complications caused by CKD.