The Bristol Sponge Microbiome Collection: A Unique Repository of Deep-Sea Microorganisms and Associated Natural Products.

Sam E Williams,Catherine R Back,James Spencer,Paul R Race,Christine L Willis,Angela E Essex-Lopresti,Paul Curnow,Henry L Stennett,Kavita Tiwari,Jorge Ojeda Gomez,Martin R Challand,Katharine R Hendry

doi:10.3390/antibiotics9080509

Abstract

The deep ocean is the largest habitat for life on Earth, though the microorganisms that occupy this unique environmental niche remain largely unexplored. Due to the significant logistical and operational challenges associated with accessing the deep ocean, bioprospecting programmes that seek to generate novel products from marine organisms have, to date, focused predominantly on samples recovered from shallow seas. For this reason, the deep ocean remains a largely untapped resource of novel microbiological life and associated natural products. Here we report the establishment of the Bristol Sponge Microbiome Collection (BISECT), a unique repository of deep-sea microorganisms and associated metabolites isolated from the microbiota of marine sponges, recovered from previously unsurveyed regions of the mid Atlantic Ocean, at depths of 0.3–3 km. An integrated biodiscovery pipeline comprising molecular, genetic, bioinformatic and analytical tools is also described, which is being applied to interrogate this collection. The potential of this approach is illustrated using data reporting our initial efforts to identify antimicrobial natural product lead compounds. Prospects for the use of BISECT to address allied pharmaceutical needs, along with mechanisms of access to the collection are also discussed

Highlights

Natural products and their derivatives are preeminent sources of lead compounds for pharmaceutical development, accounting for >50% of all small molecule-based drugs in current clinical use [1,2]
We report the establishment of the Bristol Sponge Microbiome Collection (BISECT), a growing collection of marine microorganisms isolated from a unique repository of 75 mid-Atlantic deep-sea sponge tissue samples
Allied to the development of this collection, we describe an end-to-end biodiscovery pipeline comprising a suite of in vivo, in vitro and in silico tools, which are being applied to establish the biosynthetic potential of the contents of BISECT

Summary

Introduction

Natural products and their derivatives are preeminent sources of lead compounds for pharmaceutical development, accounting for >50% of all small molecule-based drugs in current clinical use [1,2]. A further complication is that many of the microbial gene clusters that encode the biosynthetic machinery required to assemble natural product scaffolds are inactive, repressed or ‘silent’ under standard laboratory culturing conditions [7]. This combination of chemical redundancy and dormant metabolism reduces the likelihood of isolating novel bioactive compounds, even from sizeable culture collections

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Discussion

Conclusion