About this Research Topic
The marine habitat represents an untapped source of bioactive compounds with promising therapeutic potential and clinical applications. As a result of intensive bioprospecting efforts in the search of bioactive secondary metabolites from the marine environment, during the last decade there has been a considerable increase in the number of marine natural products that have been successfully launched into the drug market (i.e., Yondelis®, Adcertis®, Halaven®). In addition, numerous potential marine-derived drug candidates are currently in advanced stages of clinical development. This has partly been driven by advances in sampling and analytical techniques as well as by novel high-throughput screening platform technologies. Nevertheless, the limited supply of promising bioactive metabolites from their natural sources remains one of the major bottlenecks in marine natural products drug discovery and development.
As an alternative to the environmentally unsustainable wild harvesting, marine invertebrate aquaculture has made considerable progress in the past few years. However, despite the fact that current aquaculture practices are suitable with regard to the supply issue during the early stages of drug discovery, up to now, this strategy is not sufficient to meet market demand. Similarly, total chemical synthesis of bioactive natural products has been well established, but in many cases, it is economically unfeasible due to the high degree of structural complexity and low yields of the final products.
Marine invertebrates harbor a vast array of associated microorganisms that may even constitute up to 40-60% of their biomass. Remarkably, recent findings suggest that symbiotic microorganisms may in fact be the true source of bioactive secondary metabolites, previously attributed to their invertebrate hosts. This is also corroborated by the fact that microbial natural products often show striking structural similarities to known marine invertebrate metabolites. As such, microbial fermentation combined with chemical synthesis could pave the way towards sustainable supply of marine-derived metabolites, as exemplified by the successful semi-synthesis of the anticancer drug trabectedin (Yondelis®) from the structural analog cyanosafracin B, which is produced by large-scale fermentation of Pseudomonas fluorescens . Furthermore, culture-independent strategies, such as genome sequence and mining, as well as expression of key biosynthetic gene clusters in native or heterologous microbial hosts offer an exciting alternative for sustainable production of pharmacologically active marine metabolites.
This Frontiers Research Topic calls for original research articles and reviews that focus on the potential of emerging strategies to overcome the hurdles associated with the pressing supply problem inherent to marine drug development. Emphasis will be given on molecular genetic and microbial fermentation approaches, as viable avenues for sustainable production of marine leads. We cordially welcome all researchers broadly interested in this field to contribute their latest findings, in the hope that the marine pharmaceutical pipeline will rapidly increase in the foreseeable future.
Keywords: Marine pharmaceuticals, endosymbionts, genome mining, heterologous expression, marine microbiology
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