抗生素是由细菌等微生物和高等植物在生活过程中合成，具有抗病原体并干扰其他生物细胞发育的功能。
现在，研究人员明白了细菌合成普遍抗生素的路径，将有助于人类创建出潜力更强的新抗生素，新成果发表在日前在线出版的《自然—化学生物学》期刊上。这种调控细菌合成通道的能力为人类抗击细菌提供了新选择。
实验室中，卡那霉素通常是作为某种新基因被成功嵌入一种细菌的通用型报告剂。尽管卡那霉素广泛存在、并且几种相关的自然产物也提供了自然合成途径的线索，但是，科学家们一直不清楚细菌卡那霉是如何合成卡那霉素的。
Jae Kyung Sohng、Yeo Joon Yoon和同事合作，报告了能够解释整个卡那霉素生物合成途径的遗传学和生物化学证据。令人吃惊的是，他们发现卡那霉素家族的化合物都是通过由单个酶控制的两个平衡通道所生产。通过置换关键酶或在合成过程结束时插入其他部件，他们能够改变化合物的结构、创建出的细胞通道可生产具有临床价值的化合物妥布霉素和丁胺卡那霉素。他们发现，一种合成物“1-N-AHBA-卡那霉素X”显示出比丁胺卡那霉素更大的活性，表明它可能是对付细菌感染的一种重要工具。(生物谷 Bioon.com)
doi:10.1038/nchembio.671
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Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation
Je Won Park,Sung Ryeol Park,Keshav Kumar Nepal, Ah Reum Han, Yeon Hee Ban, Young Ji Yoo, Eun Ji Kim, Eui Min Kim, Dooil Kim, Jae Kyung Sohng & Yeo Joon Yoon .
Kanamycin is one of the most widely used antibiotics, yet its biosynthetic pathway remains unclear. Current proposals suggest that the kanamycin biosynthetic products are linearly related via single enzymatic transformations. To explore this system, we have reconstructed the entire biosynthetic pathway through the heterologous expression of combinations of putative biosynthetic genes from Streptomyces kanamyceticus in the non–aminoglycoside-producing Streptomyces venezuelae. Unexpectedly, we discovered that the biosynthetic pathway contains an early branch point, governed by the substrate promiscuity of a glycosyltransferase, that leads to the formation of two parallel pathways in which early intermediates are further modified. Glycosyltransferase exchange can alter flux through these two parallel pathways, and the addition of other biosynthetic enzymes can be used to synthesize known and new highly active antibiotics. These results complete our understanding of kanamycin biosynthesis and demonstrate the potential of pathway engineering for direct in vivo production of clinically useful antibiotics and more robust aminoglycosides.
