Synthesis and Antimicrobial Evaluation of Side-Chain Derivatives based on Eurotiumide A.

Side-chain derivatives of eurotiumide A, a dihydroisochroman-type natural product, have been synthesized and their antimicrobial activities described. Sixteen derivatives were synthesized from a key intermediate of the total synthesis of eurotiumide A, and their antimicrobial activities against two Gram-positive bacteria, methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), and a Gram-negative bacterium, Porphyromonas gingivalis, were evaluated. The results showed that derivatives having an iodine atom on their aromatic ring instead of the prenyl moiety displayed better antimicrobial activity than eurotiumide A against MSSA and P. gingivalis. Moreover, we discovered that a derivative with an isopentyl side chain, which is a hydrogenated product of eurotiumide A, is the strongest antimicrobial agent against all three strains, including MRSA.

Efficient aspartic acid production by a psychrophile-based simple biocatalyst.

We previously constructed a Psychrophile-based Simple bioCatalyst (PSCat) reaction system, in which psychrophilic metabolic enzymes are inactivated by heat treatment, and used it here to study the conversion of aspartic acid from fumaric acid mediated by the activity of aspartate ammonia-lyase (aspartase). In Escherichia coli, the biosynthesis of aspartic acid competes with that of L-malic acid produced from fumaric acid by fumarase. In this study, E. coli aspartase was expressed in psychrophilic Shewanella livingstonensis Ac10 heat treated at 50 °C for 15 min. The resultant PSCat could convert fumaric acid to aspartic acid without the formation of L-malic acid because of heat inactivation of psychrophilic fumarase activity. Furthermore, alginate-immobilized PSCat produced high yields of aspartic acid and could be re-used nine times. The results of our study suggest that PSCat can be applied in biotechnological production as a new approach to increase the yield of target compounds.

Loss of histone H4K20 trimethylation predicts poor prognosis in breast cancer and is associated with invasive activity.

INTRODUCTION: Loss of histone H4 lysine 20 trimethylation (H4K20me3) is associated with multiple cancers, but its role in breast tumors is unclear. In addition, the pathological effects of global reduction in H4K20me3 remain mostly unknown. Therefore, a major goal of this study was to elucidate the global H4K20me3 level in breast cancer tissue and investigate its pathological functions. METHODS: Levels of H4K20me3 and an associated histone modification, H3 lysine 9 trimethylation (H3K9me3), were evaluated by immunohistochemistry in a series of breast cancer tissues. Univariate and multivariate clinicopathological and survival analyses were performed. We also examined the effect of overexpression or knockdown of the histone H4K20 methyltransferases, SUV420H1 and SUV420H2, on cancer-cell invasion activity in vitro. RESULTS: H4K20me3, but not H3K9me3, was clearly reduced in breast cancer tissue. A reduced level of H4K20me3 was correlated with several aspects of clinicopathological status, including luminal subtypes, but not with HER2 expression. Multivariate analysis showed that reduced levels of H4K20me3 independently associated with lower disease-free survival. Moreover, ectopic expression of SUV420H1 and SUV420H2 in breast cancer cells suppressed cell invasiveness, whereas knockdown of SUV420H2 activated normal mammary epithelial-cell invasion in vitro. CONCLUSIONS: H4K20me3 was reduced in cancerous regions of breast-tumor tissue, as in other types of tumor. Reduced H4K20me3 level can be used as an independent marker of poor prognosis in breast cancer patients. Most importantly, this study suggests that a reduced level of H4K20me3 increases the invasiveness of breast cancer cells in a HER2-independent manner.

Acidic xylooligosaccharide preserves hepatic iron storage level in adult female rats fed a low-iron diet.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. This experiment was conducted to investigate whether acidic xylooligosaccharide (U-XOS), expected to have a high iron bioavailability, was useful in the prevention of iron deficiency. Experiment 1: Nineteen female Sprague-Dawley rats (20 wk old) were fed three different diets for 28 d; a U-XOS-supplemented low-iron diet (LI-X, n=7), a low-iron diet (LI, n=6), and a control diet (C, n=6). On day 28, the LI-X and LI groups showed iron deficiency without anemia. A significant difference in the total and unsaturated iron binding capacity, and serum transferrin saturation level was shown in the LI-X and LI groups, compared with the C group. However, the decrease of hepatic iron content of the LI-X group was suppressed compared with the LI group. Experiment 2: Eleven male Sprague-Dawley rats (7 wk old) were fed a U-XOS-supplemented diet (X, n=5) or a control diet (C, n=6) for 7 d. No significant difference in body weight gain or food intake was demonstrated between the two groups; the apparent iron absorption rate of the X group increased clearly compared with that of the C group. These results suggested that a U-XOS diet could preserve storage of hepatic iron in adult female rats fed a low-iron diet and could prevent IDA by promotion of dietary iron absorption, inhibition of iron excretion, and/or improvement of iron bioavailability.