抗生素是由細菌等微生物和高等植物在生活過程中合成,，具有抗病原體并干擾其他生物細胞發(fā)育的功能。
現(xiàn)在，研究人員明白了細菌合成普遍抗生素的路徑,，將有助于人類創(chuàng)建出潛力更強的新抗生素，新成果發(fā)表在日前在線出版的《自然—化學生物學》期刊上,。這種調(diào)控細菌合成通道的能力為人類抗擊細菌提供了新選擇,。
實驗室中，卡那霉素通常是作為某種新基因被成功嵌入一種細菌的通用型報告劑,。盡管卡那霉素廣泛存在,、并且?guī)追N相關(guān)的自然產(chǎn)物也提供了自然合成途徑的線索，但是，科學家們一直不清楚細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，報告了能夠解釋整個卡那霉素生物合成途徑的遺傳學和生物化學證據(jù),。令人吃驚的是,，他們發(fā)現(xiàn)卡那霉素家族的化合物都是通過由單個酶控制的兩個平衡通道所生產(chǎn)。通過置換關(guān)鍵酶或在合成過程結(jié)束時插入其他部件,，他們能夠改變化合物的結(jié)構(gòu),、創(chuàng)建出的細胞通道可生產(chǎn)具有臨床價值的化合物妥布霉素和丁胺卡那霉素。他們發(fā)現(xiàn),，一種合成物“1-N-AHBA-卡那霉素X”顯示出比丁胺卡那霉素更大的活性,，表明它可能是對付細菌感染的一種重要工具。(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.
