Lovastin-Producing Enzyme Moved To Yeast

A multifunctional enzyme that a fungus uses to produce the cholesterol-lowering drug lovastatin has been moved into yeast, in which it is not normally found. Not much is known about the way highly reducing iterative polyketide synthases (HR-IPKSs) such as lovastatin nonaketide synthase (LovB) work. And it’s been difficult to obtain sufficient quantities from natural fungal sources to be able to learn more about their mechanism of action. So John C. Vederas of the University of Alberta, Yi Tang of UCLA, and coworkers transferred LovB from Aspergillus terreus into the yeast Saccharomyces cerevisiae (Science 2009, 326, 589). By studying purified LovB from yeast in the presence and absence of cofactors and a partner enzyme, LovC, the researchers were able to discover new details about the way LovB produces dihydromonacolin L, the substrate for lovastatin’s commercial biosynthesis. The work shows that LovB disposes of incorrectly processed intermediates as pyrones and hydrolytic products. This approach “provides a basis for understanding the programming rules of HR-IPKSs,” the researchers write.