一些生物化学过程被认为已经被研究得非常完整，因此科学家相信不会再取得任何这方面的发现。但是最近Johns Hopkins大学的科学家的发现推翻了这个理论，他们确认了一种30年来一直是个谜的酶。该结果发表在《结构》（Structure）上。
作者之一，Hopkins生物物理和生物物理化学教授L. Mario Amzel说：“当我们意识到发现的是细菌制造维生素B叶酸的酶时，我们非常惊讶，因为从1974年开始科学家就知道应该存在这样一种物质。”
Amzel和同事Maurice Bessman当时在系统研究细菌中一组相关的酶如何识别特定的分子，对于每一种酶，科学家都进行纯化分离。然后使它们生长出晶体，再利用X射线等技术分析出酶的三维结构。有了三维结构，小组就可以利用计算机模型分析酶如何和另一个分子结合和发生相互作用。
文章作者Sandra Gabelli说：“在Maurice开始搜寻旧资料前我们并未觉得这有何特别的，结果发现Suzuki和合作者在1974年发表文章称大肠杆菌中存在一种和我们类似的酶，它能发动叶酸的生物合成。”
Amzel说：“因此我们问，去除了orf17基因的细菌是否能制造叶酸。”Bessman和同事因此去除了这一基因，结果和预想的一样，细菌制造的叶酸比正常时少了10倍。细菌制造叶酸的机制对于希望设计更有效的抗生素药物的科学家而言非常重要。人类无法进行叶酸合成，因此设计针对细菌叶酸合成机制的药物不会对人类产生副作用。
Amzel认为他们找到了潜在的杀菌目标，他说：“我们并非药物设计行业的一员，而只是致力于基础研究。我们希望取得的发现能帮助其他人发明新的药物。”
原文报道：
Folate mystery finally solved
The accompanying image illustrates the stages of enzyme activity of the first step of folate biosynthesis: free enzyme (orange), enzyme with substrate bound (salmon), and enzyme with pyrophosphate bound (gold), superimposed on a drawing of E. coli and the folate biosynthetic pathway. The free floating substrate is shown in blue, with the phosphates in red. Credit: The rendition was contributed by Devon Nikasa an alumna of the Art as Applied to Medicine Program at Hopkins.
Some biochemical processes, especially those in bacteria, have been so well studied it’s assumed that no discoveries are left to be made. Not so, it turns out, for Johns Hopkins researchers who have stumbled on the identity of an enzyme that had been a mystery for more than 30 years. The report appears in the May 15 issue of Structure.
“It was really quite a surprise when we realized we had discovered the unknown player in how bacteria make the B vitamin folate, a player that we’ve known of since 1974,” says study author L. Mario Amzel, Ph.D., professor and director of biophysics and biophysical chemistry at Hopkins. “Basic research can be so serendipitous at times.”
Amzel and colleague Maurice Bessman and their labs were in the middle of systematically characterizing how members of a family of related enzymes in bacteria can recognize specific molecules. With each family member, they isolated purified enzyme, grew crystals of pure enzyme, and figured out the enzyme’s 3-D structure by using techniques that use X-rays.
Armed with the 3-D structure, they then used computer modeling to analyze how the enzyme binds to and acts on another molecule, its substrate.
“We still didn’t know that it was anything special until Maurice started searching old publications,” says study author Sandra Gabelli, Ph.D. “As it turns out, Suzuki and coworkers in 1974 had published evidence of an enzyme in the bacteria E. coli with similar characteristics to ours that could initiate folate biosynthesis.”
“So we had to ask, Can the bacteria make folate if we remove the orf17 gene"” says Amzel. Bessman and colleagues then “knocked-out” the gene and, predictably, the bacteria made 10 times less folate than usual.
“It was such a sweet discovery,” says Gabelli. “It’s scientific discovery the old-fashioned way, finding something we weren’t looking for.”
The mechanics behind how bacteria make folate are of particular interest to scientists who want to design more powerful antibacterial drugs. Humans cannot make folate because they do not have any of the same molecular machinery. Therefore, it’s possible to design drugs that target the bacterial folate machinery that would not lead to side effects in humans.
Their discovery, says Amzel, identifies yet another potential antibacterial target. “We are not in that business of drug design—we’re focused on the basics, figuring out how things work,” he says. “We do hope that others can use what we find to make new drugs.”
Source: Johns Hopkins Medical Institutions
