Creating a Spinoff

See allHide authors and affiliations

Science  23 Jan 2009:
Vol. 323, Issue 5913, pp. 438
DOI: 10.1126/science.323.5913.438b

How might one acquire a new catalytic ability? Other than by stealing an enzyme (akin to lateral gene transfer), one could take advantage of an existing but suboptimal active site. Sánchez-Moreno et al. describe the promiscuous behavior of the decidedly un-sexy protein dihydroxyacetone kinase (DHAK), whose generally accepted role is to use ATP to phosphorylate the metabolite dihydroxyacetone; the product, dihydroxyacetone phosphate, can be used in lipid and carbohydrate biosynthesis, whereas the unphosphorylated substrate is toxic. What these authors document is that DHAK (shown at left) also catalyzes the FAD-AMP lyase reaction, in which the cofactor FAD is split into AMP and a molecule of riboflavin 4′,5′-phosphate. A key point is that the lyase reaction proceeds with roughly the same catalytic efficiency as the kinase reaction, albeit significantly more slowly and with a requirement for Mn2+ instead of Mg2+. Intriguingly, the intracellular concentration of Mn is much lower than that of Mg, yet several other carbohydrate-handling enzymes, such as pyruvate kinase, are also manganese-dependent. — GJC

ChemBioChem 10, 10.1002/cbic.200800573 (2009).

Navigate This Article