MINNEAPOLIS-ST. PAUL—Microorganisms are a great source of molecular diversity in the search for new chemical entities to be turned into drugs. Unfortunately, problems with large-scale fermentation of some organisms limit their utility as a source of these compounds. Recently, researchers at the University of Minnesota, University of Michigan, and University of Hawaii examined the challenge of producing anticancer cryptophycins in blue-green algae.
As discussed in Chemical Biology, the researchers combined molecular biology and bioinformatics to identify, clone, and sequence enzymes involved in the biosynthesis of the main cryptophycin analogue. They found that unlike many enzymes that are very specific in their substrate selectivity, the algal genes were quite flexible, allowing for an expanded range of analogues and intermediates.
The researchers then tested this theory by altering the choice of biosynthetic intermediates available to the algae and produced a series of novel cryptophycin compounds. The findings open the door to further studies involving a combination of chemo- and biosynthesis to expand the range of potential anticancer drugs.