HOBOKEN, N.J. Stevens Institute of Technologys Professor Athule B. Attygalle and his doctoral student Kithsiri B. Herath have collaborated with Merck Pharmaceuticals Dr. Sheo B. Singh on a study whose findings have been published in the Journal of the American Chemical Society, in a paper titled Biosynthetic Studies of Platensimycin (Herath, K. B.; Attygalle, A. B.; Singh, S. B. J. Am. Chem. Soc.; [Communication]; 2007; ASAP Article; DOI: 10.1021/ja0758943from academia and industry).
It reports biosynthesis of a novel antibiotic, said Attygalle. It is the product of a rewarding research effort done with Merck, with Dr. Singhs participation.
Platensimycin (1) and platencin (2), two novel antibiotics, were recently isolated from several strains of Streptomyces platensis.
They impart their potent Gram-positive antibacterial activity, including that against drug-resistant organisms (e.g., MRSA, VRE), by uniquely inhibiting acyl enzyme intermediates of the condensing enzymes FabF and FabF/FabH, respectively, vital for fatty acid biosynthesis.
Both compounds are highly efficacious in vivo when administered by continuous infusion; however, the efficacy is reduced when administered by conventional routes. This phenomenon is attributed to their poor pharmacokinetic properties which could potentially be improved by chemical modification of the natural product, via total synthesis and through combinatorial biosynthesis.
Understanding biosynthetic pathways leading to the biosynthesis of both compounds is a prerequisite for combinatorial biosynthesis and is also helpful for improvement of the titer of these compounds in the producing organism. The report details the resultsof biosynthetic studies of platensimycin by stable-isotope precursor incorporation experiments.
|Contact: Patrick A. Berzinski|
Stevens Institute of Technology