GENE MACHINE TRUMPS SYNTHESIS

Abstract

IN ANOTHER DEMONSTRATION of the power of metabolic engineering, researchers have developed a fungus that produces derivatives of a bioactive natural product that cannot be made efficiently using chemical synthesis. The natural product is the cyclooctadepsipeptide PF1022A. It consists of four residues of N -methyl-L-leucine alternating with two residues each of D-lactate and D-phenyllactate. Its potent activity against nematodes makes it a strong candidate to replace existing agents, to which resistance is increasing. Studies have shown that derivatives of PF1022A in which the para positions of the benzene units are substituted with amino or nitro groups are even more potent against parasitic worms than the original natural product. Chemical methods to introduce substituents at the benzenes' para positions are low yielding and inefficient for industrial-scale production. For this reason, Koji Yanai and coworkers at Meiji Seika Kaisha, in Kanagawa Japan, turned to metabolic engineering. By modifying a filam...