There is a continuous need for novel microbial natural products to fill the drying‐up drug development pipeline. Herein, we report myxadazoles from Myxococcus sp. SDU36, a family of novel chimeric small molecules that consist of N‐ribityl 5,6‐dimethylbenzimidazole and a linear fatty acid chain endowed with an isoxazole ring. The experiments of genome sequencing, gene insertion mutation, isotope labelling, and precursor feeding demonstrated that the fatty acid chain was encoded by a non‐canonical PKS/NRPS gene cluster, whereas the origin of N‐ribityl 5,6‐dimethylbenzimidazole was related to the vitamin B12 metabolism. The convergence of these two distinct biosynthetic pathways through a C‐N coupling led to the unique chemical framework of myxadazoles, which is an unprecedented hybridization mode in the paradigm of natural products. Myxadazoles exhibited potent vasculogenesis promotion effect and moderate antithrombotic activity, underscoring their potential usage for the treatment of cardiovascular diseases.

Phospholipids (PLs) are important components of physiological metabolism in animals and plants, and they have been widely used in clinical treatment, cosmetics, and industry. With the development of marine resources, marine PLs rich in polyunsaturated fatty acids have attracted increasing attention. As important marine resources, shrimp heads (SH), codfish roe (CR), and squid gonads (SG) contain a high PL content.The antithrombotic, antistroke, anti-inflammatory, pro-angiogenic, and cardioprotective activities of PLs from SH, CR, and SG were evaluated and compared using the in vivo zebrafish model. The results showed that the PL extracts of SH, CR, and SG had significant biological activities, which lays a theoretical foundation for the development and utilization of PLs in marine byproducts in the future, providing a new choice for the prevention of inflammatory and cardiovascular diseases.

In this study, the anti‐atherosclerotic properties of three marine phospholipids (MPLs) extracts from fishery by‐products including codfish roe, squid gonad, and shrimp head are verified. Their effects on key factors involved in atherosclerosis are examined and compared to explore whether the differences in their constitutions lead to the differences in the function. All three MPLs dampen oxidation of low‐ density lipoproteins (LDL) in vitro. Treating RAW264.7 macrophages and HUVECs endothelial cells with each MPLs ranging 10–100 µg mL−1 does not decrease cell viability, yet ox‐LDL caused cytotoxicity of both cells are alleviated by 50 or 100 µg mL−1 MPLs treatment. In addition, the three MPLs reduce ox‐LDL induced macrophage foam‐like transition, mainly through inhibition of lipid uptake. Of the three MPLs, the one from squid gonad exhibits the best effect. On the other hand, all three MPLs modulate inflammatory responses, equally, by inhibiting the adhesion of monocytes to endothelial cells, and decreasing secretion of pro‐inflammatory cytokines IL‐6 and MCP‐1. Using a high‐cholesterol diet induced zebrafish model, it is found that all three MPLs, especially the one from squid gonad, alleviates cholesterol accumulation in early plaques, and decreases total cholesterol as well as lipid peroxide in vivo. Practical Applications: As a way of making the best of the increasingly scarce marine resources, valuable lipid components can be recovered from by‐products and wastes from the fishery industry. Here, we tested the anti‐atherosclerotic effects and the mechanisms of three MPLs extracted from codfish roe, squid gonad, and shrimp head. Our study provides further evidence that marine phospholipids extracted from fishery by‐products could protect against atherosclerosis, and helps to elucidate the structure‐function relationship of MPLs.