A new polyene macrolide antibiotic, machidamycin, produced by Streptomyces sp. K22-0017.

A new polyene macrolide, machidamycin (1), and a known compound YS-822A (2), were obtained by physicochemical screening from a culture broth of Streptomyces sp. K22-0017. The structures were elucidated using MS and 1D/2D NMR analyses. Compound 1 exhibited weak antifungal activity against Candida albicans and Mucor racemosus. Furthermore, 1 showed stronger antileishmanial activity than the existing drug paromomycin.

Dietary oleic acid intake increases the proportion of type 1 and 2X muscle fibers in mice.

Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear. This study aimed to determine the effect of oleic acid on the muscle fiber types and endurance capacity. An in vivo mouse model was used, and mice were fed a 10% oleic acid diet for 4 weeks. Two different skeletal muscles, slow soleus muscle with the predominance of slow-twitch fibers and fast extensor digitorum longus (EDL) muscle with the predominance of fast-twitch fibers, were used. We found that dietary oleic acid intake improved running endurance and altered fiber type composition of muscles, the proportion of type 1 and 2X fibers increased in the soleus muscle and type 2X increased in the EDL muscle. The fiber type shift in the EDL muscle was accompanied by an increased muscle TAG content. In addition, blood triacylglycerol (TAG) and non-esterified fatty acid levels decreased during exercise. These changes suggested that lipid utilization as an energy substrate was enhanced by oleic acid. Increased proliferator-activated receptor γ coactivator-1ß protein levels were observed in the EDL muscle, which potentially enhanced the fiber type transitions towards type 2X and muscle TAG content. In conclusion, dietary oleic acid intake improved running endurance with the changes of muscle fiber type shares in mice. This study elucidated a novel functionality of oleic acid in skeletal muscle fiber types. Further studies are required to elucidate the underlying mechanisms. Our findings have the potential to contribute to the field of health and sports science through nutritional approaches, such as the development of supplements aimed at improving muscle function.

Chloride Ions Stabilize Human Adult Hemoglobin in the T-State, Competing with Allosteric Interaction of Oxygen Molecules.

In the context of a molecular-level understanding of the allostery mechanisms, human adult hemoglobin (HbA) has been extensively studied for over half a century. Chloride ions (Cl-) have been known as one of HbA allosteric effectors, which stabilizes the T-state preferable to release oxygen molecules. The functional mechanisms were individually proposed by Ueno and Perutz several decades ago. Ueno considered that the site-specific Cl- binding is essential, while Perutz proposed the non-site-specific interaction between HbA and Cl-. Each speculation explains the mechanism plausibly since each was tightly associated with its reasonable experimental observation. However, both mechanisms themselves still seem to make their speculations controversial. In the present study, we have theoretically reconsidered these apart from their approaches. Our atomistic molecular dynamics simulations then showed that the increase of Cl- concentration suppresses the conformational conversion from the T-state. Interestingly, chloride ions loosely interact with the amino acid residues inside the HbA central cavity, suggesting that both Perutz's and Ueno's speculations are involved in understanding the microscopic roles of Cl-. In conclusion, we theoretically certified that the effect of Cl- competes against that of solvated O2, i.e., the destabilization of T-state through the non-site-specific interaction, implying the concerted regulation of HbA under physiological conditions.