HOBOKEN, N.J. ¯ Stevens Institute of Technology’s Professor Athule B. Attygalle and his doctoral student Kithsiri B. Herath have collaborated with Merck Pharmaceutical’s 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. Singh’s 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.
About Stevens Institute of Technology
Founded in 1870, Stevens Institute of Technology is one of the leading technological universities in the world dedicated to learning and research. Through its broad-based curricula, nurturing of creative inventiveness, and cross disciplinary research, the Institute is at the forefront of global challenges in engineering, science, and technology management. Partnerships and collaboration between, and among, business, industry, government and other universities contribute to the enriched environment of the Institute. A new model for technology commercialization in academe, known as Technogenesis®, involves external partners in launching business enterprises to create broad opportunities and shared value. Stevens offers baccalaureates, master’s and doctoral degrees in engineering, science, computer science and management, in addition to a baccalaureate degree in the humanities and liberal arts, and in business and technology. The university has a total enrollment of 2,040 undergraduate and 3,085 graduate students, and a worldwide online enrollment of 2,250, with about 400 full-time faculty. Stevens’ graduate programs have attracted international participation from China, India, Southeast Asia, Europe and Latin America. Additional information may be obtained from its web page at www.stevens.edu.
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Journal
Journal of the American Chemical Society