Polycyclic tetramate macrolactams (PoTeMs) are a family of natural products containing a tetramic acid moiety and a polycyclic system. Due to the valuable biological activities of different PoTeMs and the genetic simplicity of their biosynthetic genes, it is highly desirable to manipulate the biosynthesis of PoTeMs by swapping modification genes between different pathways. Herein, by combining the cytochrome P450 (CYP) enzymes from different PoTeM pathways with the combamides’ biosynthetic genes, the new combamides G (3), I (5), and J (6) along with the known combamides B (1), D (2), and H (4) were identified from the recombinant strains. Combamides G (3), H (4), and J (6) displayed cytotoxic activity against human cancer cell lines. Furthermore, our results demonstrated for the first time the substrate specificity of the PoTeM-related CYPs in vivo, which will facilitate the engineered biosynthesis of other PoTeMs in the future.

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焦玉杰 †,a 颜雅倩 †,a 刘 焱 a 朱德裕 b 沈月毛 * ,a 李瑶瑶 * ,a ( a 山东大学药学院 天然产物化学生物学教育部重点实验室 济南 250012) ( b 山东大学基础医学院 济南 250012) 摘要 从链霉菌 S001 的重组菌株 S001-PoTeM S023 中分离获得 1 个结构新颖的含有 5/5/6 三环体系的多环特特拉姆酸大 环内酰胺(PoTeMs)类化合物 montamide A (1), 通过一维和二维核磁(NMR)、高分辨质谱和圆二色谱确定了其化学结构.

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Manure application is an effective way to improve the utilization efficiency of organic resources and alleviate the adverse effects of long-term application of chemical fertilizers. However, the impact of applying manure under different nitrogen rates on soil microbial community in wheat field remains unclear. Treatments with and without chicken manure application under three nitrogen rates (N 135, 180 and 225 kg⋅hm–2) were set in wheat field. Soil organic carbon, available nutrients, and abundance, diversity, structure and co-occurrence pattern of soil microbial community at wheat maturity were investigated. Compared with no manure application, chicken manure application increased the soil organic carbon and available phosphorus, while the effects on soil mineral nitrogen and available potassium varied with different nitrogen rates. Chicken manure application significantly increased soil bacterial abundance under the nitrogen fertilization of 135 and 225 kg⋅hm–2, increased soil fungal abundance under the nitrogen fertilization of 135 kg⋅hm–2, but decreased soil fungal abundance under the nitrogen fertilization of 180 and 225 kg⋅hm–2 (P < 0.05). There was no significant difference in alpha diversity indices of soil microbial communities between treatments with and without chicken manure application under different nitrogen rates (P > 0.05). Chicken manure application and its interaction with nitrogen rate significantly changed soil bacterial and fungal community structures (P < 0.05). There were significantly different taxa of soil microbial communities between treatments with and without chicken manure application. Chicken manure application reduced the ecological network complexity of soil bacterial community and increased that of soil fungal community. In summary, the responses of soil available nutrients and microbial abundance to applying chicken manure varied with different nitrogen rates. One growing season application of chicken manure was sufficient to alter the soil microbial community structure, composition and co-occurrence pattern, whereas not significantly affected soil microbial community diversity.