Engineering the precursor supply pathway in Streptomyces gilvosporeus for overproduction of natamycin / 生物工程学报

Natamycin is a safe and efficient antimycotics which is widely used in food and medicine industry. The polyene macrolide compound, produced by several bacterial species of the genus Streptomyces, is synthesized by type Ⅰ polyketide synthases using acetyl-CoA, malonyl-CoA, and methylmalonyl-CoA as substrates. In this study, four pathways potentially responsible for the supply of the three precursors were evaluated to identify the effective precursor supply pathway which can support the overproduction of natamycin in Streptomyces gilvosporeus, a natamycin-producing wild-type strain. The results showed that over-expressing acetyl-CoA synthetase and methylmalonyl-CoA mutase increased the yield of natamycin by 44.19% and 20.51%, respectively, compared with the wild type strain under shake flask fermentation. Moreover, the yield of natamycin was increased by 66.29% compared with the wild-type strain by co-overexpression of acetyl-CoA synthetase and methylmalonyl-CoA mutase. The above findings will facilitate natamycin strain improvement as well as development of strains for producing other polyketide compounds.

Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

Methylation, acetylation and phosphorylation of the bases of DNA of young and old rats.

The possibility of methylation, acetylation and phosphorylation of the bases of DNA has been studied in vitro by incubating nuclei of the liver and cerebral hemisphere of young (18 wk) and old (120 wk) rats with radioactive donors, [3H]S approximately adenosyl methylmethionine, [3H]-acetyl approximately CoA and [32P]-gamma-ATP for methylation, acetylation and phosphorylation of the bases, respectively. Nuclei were also incubated with S approximately adenosyl homocysteine to inhibit methylation with sodium butyrate to stimulate acetylation and with alkaline phosphatase to remove phosphate groups incorporated into the bases. DNA was then extensively purified and incorporation of each type of label was estimated. The data show that both methylation and acetylation of DNA of old rats were significantly higher than those of young rats, and phosphorylation is lower in old rats. Such modifications may prevent base pairing between the two strands of DNA, alter its conformation and binding of trans-acting factors at specific sites, and thereby alter gene expression.