Biosynthesis of Bioactive Natural Products Derived from Theonellidae Family Marine Sponges

Abstract

Marine sponges are among the most primitive animals and often contain unique, biologically active compounds. Several of these compounds have played an important roles as pharmaceutical leads for anti-cancer drugs, such as halichondrin B, which led to the development of an anti-breast cancer drug. Some compounds with remarkable biological activities are accumulated in significantly high concentrations in the sponge. How and why the marine sponges produce and accumulate bioactive natural products are long-standing questions with both biochemical and ecological implications, since in sponges, the animal-microbe symbioses are presumed to be responsible for the biosynthetic machinery, consisting of efficient enzymes and regulatory systems for the specific biological activities of medicinally relevant natural products. In this review, I focus on the chemically rich Theonellidae family sponges and discuss the biosynthesis of bioactive peptides and polyketides. In particular, the biosynthetic pathway of calyculin A suggests that crosstalk between the sponge host and bacterial symbiont confers a chemical defense system on the immobile animal-microbe holobiont.

Global metabolome changes induced by environmentally relevant conditions in a marine-sourcedPenicillium restrictum

“…This observation may be explained by (1) the presence of signal metabolites in the mussel extract that initiates such unusual FAs production, or more likely by (2) the presence of their precursors in the mussel extract that can be incorporated in fungal biosynthetic pipelines leading to complex lipids such as triglycerides or phospholipids that include these exogenous FAs. Such production of natural products through mixed biogenetic origins have been few demonstrated so far but it is hypothetised for the biosynthesis of brominated alkaloids from sponge and their endosymbiotic microorganisms [92], for the arginine-citrulline biosynthetic loop in the Amphimedon queenslandica holobiont [93] and for the sponge/bacterium mixed origin of calyculin A [94]. In our model, such phenomenon would be particularly interesting to confirm through targeted lipid purification or deep investigation of the two protagnonists genomes.…”

Impact of Marine Chemical Ecology Research on the Discovery and Development of New Pharmaceuticals

“…In some cases, the interdependent relationship between the sponge host and the microbes could lead to the maintenance of specific microbial ‘super producers’ with high numbers of biosynthetic gene clusters. For instance, the uncultivated filamentous bacterium “ Candidatus Entotheonella” was discovered to produce almost all the defensive molecules—including polyketides such as onnamide A ( 39 ) and misakinolide A ( 40 ) and peptides such as theonellamide A ( 41 )—previously isolated from sponges of the genus Theonella ( Figure 7 ) [ 90 , 91 ]. In contrast, multiple genera of endosymbiotic microbes, namely “Entomycale ignis”, “Patea custodiens” and “Caria hoplite”, which were found to be associated with the New Zealand sponge, Mycale hentscheli , were found to cooperatively contribute to an array of defensive molecules, including mycalamide A ( 42 ), pateamine A ( 43 ) and polytheonamide-type gananamides of the holobiont ( Figure 7 ) [ 92 ].…”