New Methods for Medicinal Chemistry - Universal Gene Cloning and Expression Systems for Production of Marine Bioactive Metabolites

Walter   C.   Dunlap; Marcel      Jaspars; Daslav      Hranueli; Christopher   N.   Battershill; Natasa      Peric-Concha; Jurica      Zucko; Stephen   H.   Wright; Paul   F.   Long

doi:10.2174/092986706776055643

Abstract

Natural products from symbiotic or commensal associations between marine invertebrate and microbial organisms show exceptional promise as pharmaceuticals in many therapeutic areas. An economic and sustainable global market supply due to difficulty of synthesis is cited as the main obstacle for exploitation of these otherwise exciting marine bioactive compounds [1]. Different strategies have been evoked to overcome this impediment as long-term harvesting of wild stocks from the environment is considered unsound, and other modes of production based on biosynthesis, such as aquaculture, have not yet been proven as reliable [2]. One option is to clone the genes encoding the biosynthetic expression of a lead metabolite into a surrogate host suitable for industrial-scale fermentation. To facilitate this goal we are developing a universal system to clone and express genes responsible for biosynthesis of natural products from both eukaryotic and prokaryotic partners of marine symbioses. The ability to harness the complete meta-transcriptome of entire biosynthetic pathways is particularly valuable where the biogenesis of a target natural product occurring within a complex symbiotic association is unclear.

Keywords: Marine science, microbial genetics, marine natural products, drug development, heterologous expression, metagenomic cloning, bioinformatics, genomics screening