Novel Natural Product Discovery from Marine Sponges and their Obligate Symbiotic Organisms

Abstract

Discovery of novel natural products is an accepted method for the elucidation of pharmacologically active molecules and drug leads. Best known sources for such discovery have been terrestrial plants and microbes, accounting for about 85% of the approved natural products in pharmaceutical use (1), and about 60% of approved pharmaceuticals and new drug applications annually (2). Discovery in the marine environment has lagged due to the difficulty of exploration in this ecological niche. Exploration began in earnest in the 1950's, after technological advances such as scuba diving allowed collection of marine organisms, primarily at a depth to about 15m. Natural products from filter feeding marine invertebrates and in particular, sponges, have proven to be a rich source of structurally unique pharmacologically active compounds, with over 16,000 molecules isolated thus far (3, 1) and a continuing pace of discovery at hundreds of novel bioactive molecules per year. All classes of pharmaceuticals have been represented in this discovery process, including antiprotazoals, pesticides, TGF-beta inhibitors, cationic channel blockers, anticancer, cytotoxic, antiviral, anti-inflammatory and antibacterial compounds. Important biosynthetic pathways found in sponges which give rise to these compounds include the terpenoid (4), fatty acid, polyketoid, quinone reductase, alkaloid, isoprenoid (5), and non-ribosomal protein synthase pathways.

An Overview on Marine Sponge-Symbiotic Bacteria as Unexhausted Sources for Natural Product Discovery

“…Sponges are sessile, ancient metazoans from the phylum Porifera [49, [54][55][56][57] that date back about 600 million years [58,59] and the fact that sponges have survived in different and extreme environments for as long as they have demonstrates that modern sponges are highly evolved and successful organisms [60]. Approximately 8500 valid sponge species have been described to date [61].…”

“…Marine-derived bioactive compounds have been reported to have functional roles within their symbiotic environments as well as have biotechnological uses as antimicrobials, anticancer agents, pigments, vitamins, and enzymes used in industry [141][142][143][144][145]. These compounds, that in nature are produced as a defense against competitors, predators, and pathogens [20,107,115,146] providing the host organism with competitive advantages in the environment by increasing their access to space and nutrients through elimination of the competitors [6,57,147], may exhibit antibacterial, antiviral, antifungal, antimicrobial, or cytotoxic properties that can and have been used in therapeutic agents in the pharmaceutical industry [106,148,149]. Examples of bioactive compounds produced by sponge-associated bacteria are given in Table 2.…”

“…While culture-dependent isolation methods based on the nutritional requirements of taxonomically close relatives can provide information on the microorganisms of interest, advances in genomics, metagenomics, proteomics, transciptomics, and expression systems currently enable the discovery and production of novel compounds while completely bypassing the laboratory cultivation process of the organisms of interest [57,113,194]. …”

“…To extract biotechnologically relevant information from metagenomic libraries, two diverse types of analyses have been used. The first approach targets function (libraries are screened for the expression of specific traits), and the second one is based on screening for specific sequences [52,57,194,[199][200][201].…”

“…Metagenomic techniques have enabled the discovery of novel gene clusters particularly those responsible for polyketide synthases (PKS), non-ribosomal peptide synthases (NRPS), isoprenoid synthases, and terpenoid synthases [57,113,[203][204][205]. Many studies on PKS and NRPS gene clusters from the sponge metagenome have also found that they are most closely related to other sponge-derived sequences suggesting the possibility of sponge-specific clusters [204][205][206].…”