Abstract：
Octacosamicin A is an antifungal metabolite featuring a linear polyene-polyol chain flanked by N-hydroxyguanidine and glycine moieties. We report here that sub-inhibitory concentrations of streptomycin elicited the production of octacosamicin A in Amycolatopsis azurea DSM 43854T . We identified the biosynthetic gene cluster (oca BGC) that encodes a modular polyketide synthase (PKS) system for assembling the polyene-polyol chain of octacosamicin A. Our analysis suggested that the N-hydroxyguanidine unit originates from a 4-guanidinobutyryl-CoA starter unit, while the PKS incorporates an α-hydroxyketone moiety using a (2R)-hydroxymalonyl-CoA extender unit. The modular PKS system contains a non-canonical terminal module that lacks thioesterase (TE) and acyl carrier protein (ACP) domains, indicating the biosynthesis is likely to employ an unconventional and cryptic off-loading mechanism that attaches glycine to the polyene-polyol chain via an intermolecular amidation reaction.
摘要：
OctacosamicinA是一种抗真菌代谢物，其特征在于线性多烯多元醇链，侧翼为N-羟基胍和甘氨酸部分。我们在这里报告说，链霉素的亚抑制浓度引起了阿氮脲酰胺DSM43854T中八合霉素A的产生。我们确定了生物合成基因簇（ocaBGC），该基因簇编码模块聚酮化合物合酶（PKS）系统，用于组装八合卡霉素A的多烯多元醇链。我们的分析表明，N-羟基胍单元源自4-胍丁酰基-CoA起始单元，而PKS使用（2R）-羟基丙二酰-CoA延伸剂单元并入了α-羟基酮部分。模块化PKS系统包含一个缺乏硫酯酶（TE）和酰基载体蛋白（ACP）结构域的非规范末端模块，表明生物合成可能采用非常规和隐秘的卸载机制，该机制通过分子间酰胺化反应将甘氨酸连接到多烯多元醇链。
