Capturing Mother Nature at work: seeing how plants make vitamin B6

Vitamins are essenBal for life. They perform a huge variety of tasks within metabolism, with many helping to promote biochemical reacBons in our bodies. In general, we cannot make vitamins from scratch, and so we must obtain them from our diet. Plants and microorganisms can make these compounds de novo, and are therefore a good source of vitamins for humans, which is why it’s essenBal that we incorporate such resources within a healthy, varied diet. The study of vitamins is important for an understanding of health but it is also crucial in combaBng many infecBous diseases. Ideally, treatments for microbial infecBons are designed to target essenBal funcBons of the microbes that do not overlap with what humans and animals have, i.e. killing the microbes while leaving our bodies free from harmful side effects. For this reason, drugs that target vitamin producBon in pathogens would be ideal candidates for new anBbioBcs a goal of growing importance in a world of increasing anBbioBc resistance as humans cannot produce vitamins. The B vitamins are a family of eight different vitamins. One of these vitamins, vitamin B6, is involved in hundreds of biochemical reacBons— more than any other known nutrient—and so vitamin B6 deficiency is linked to a vast range of diseases from anaemia to epilepBc-like convulsions in infants and depression in adults. Biological organisms drive chemical reacBons using enzymes, miniature protein machines, which speed up reacBons. Plants make vitamin B6 with an enzyme called vitamin B6 synthase, which coordinates a long sequence of diverse reacBons, much like a biochemical version of an industrial producBon line. This producBon line is split between two locaBons within the physical structure of the enzyme itself (called the acBve sites). This is unusual: most enzymes promote just one or two kinds of reacBons, before passing their products on to another enzyme to conBnue the biochemical manufacturing process. As most enzymes are much too small to see by eye, even with the most powerful light microscopes, scienBsts use a technique called Xray crystallography to capture snapshots of these miniature machines at work. When water evaporates from a soluBon, the material that is leZ behind may sBck together in a regular arrangement, forming a crystal. This is the process that produces salt crystals on rocks along a sea-shore, or sugar crystals around the rim of a honey jar. Enzymes can crystallise out of soluBon in this way too. Such crystals produce pa\erns when illuminated with X-rays, from which the 3D architecture of the enzyme can be determined. Solving 3D models of enzymes in the presence of the compounds they use for their reacBons, e.g. metabolites, allow scienBsts to decipher how these machines work. Researchers at the University of Geneva purified vitamin B6 synthase found in the plant, thale cress (Arabidopsis thaliana), and determined its structure by X-ray crystallography. They discovered that it forms a double ring, containing 12 copies of the enzyme, resembling two doughnuts stacked on top of one another. They were able to see the two different sites where vitamin B6 is manufactured in the enzyme; and, where they expect raw materials are brought in, and the products released. Vitamin B6 synthase uses three different chemical ingredients to build vitamin B6. The 1: Department of Botany and Plant Biology, University of Geneva, Switzerland