Institute of Organic Chemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 18, 72076, Tübingen, Germany.
Microbiology, Organismic Interactions, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.
Nat Commun. 2019 Feb 1;10(1):545. doi: 10.1038/s41467-019-08476-8.
Antimetabolites are small molecules that inhibit enzymes by mimicking physiological substrates. We report the discovery and structural elucidation of the antimetabolite 7-deoxy-sedoheptulose (7dSh). This unusual sugar inhibits the growth of various prototrophic organisms, including species of cyanobacteria, Saccharomyces, and Arabidopsis. We isolate bioactive 7dSh from culture supernatants of the cyanobacterium Synechococcus elongatus. A chemoenzymatic synthesis of 7dSh using S. elongatus transketolase as catalyst and 5-deoxy-D-ribose as substrate allows antimicrobial and herbicidal bioprofiling. Organisms treated with 7dSh accumulate 3-deoxy-D-arabino-heptulosonate 7-phosphate, which indicates that the molecular target is 3-dehydroquinate synthase, a key enzyme of the shikimate pathway, which is absent in humans and animals. The herbicidal activity of 7dSh is in the low micromolar range. No cytotoxic effects on mammalian cells have been observed. We propose that the in vivo inhibition of the shikimate pathway makes 7dSh a natural antimicrobial and herbicidal agent.
代谢物拮抗剂是通过模拟生理底物来抑制酶的小分子。我们报告了代谢物 7-脱氧-壳七糖（7dSh）的发现和结构阐明。这种不寻常的糖抑制了各种原养型生物的生长，包括蓝藻、酿酒酵母和拟南芥等物种。我们从蓝藻集胞藻中分离出具有生物活性的 7dSh。使用集胞藻转酮醇酶作为催化剂和 5-脱氧-D-核糖作为底物的化学酶合成 7dSh，允许进行抗菌和除草的生物分析。用 7dSh 处理的生物体积累 3-脱氧-D-阿拉伯庚酮糖酸 7-磷酸，这表明分子靶标是 3-脱氢奎宁酸合酶，它是莽草酸途径的关键酶，在人和动物中不存在。7dSh 的除草活性在低微摩尔范围内。对哺乳动物细胞没有观察到细胞毒性作用。我们提出，体内抑制莽草酸途径使 7dSh 成为一种天然的抗菌和除草剂。
