Terpene biosynthesis in marine sponge animals

Abstract

Sea sponges are the largest marine source of small-molecule natural products described to date. Sponge-derived molecules, such as the chemotherapeutic eribulin, the calcium-channel blocker manoalide, and antimalarial compound kalihinol A, are renowned for their impressive medicinal, chemical, and biological properties. Sponges contain microbiomes that control the production of many natural products isolated from these marine invertebrates. In fact, all genomic studies to date investigating the metabolic origins of sponge-derived small molecules concluded that microbes—not the sponge animal host—are the biosynthetic producers. However, early cell-sorting studies suggested the sponge animal host may play a role particularly in the production of terpenoid molecules. To investigate the genetic underpinnings of sponge terpenoid biosynthesis, we sequenced the metagenome and transcriptome of an isonitrile sesquiterpenoid-containing sponge of the order Bubarida. Using bioinformatic searches and biochemical validation, we identified a group of type I terpene synthases (TSs) from this sponge and multiple other species, the first of this enzyme class characterized from the sponge holobiome. The Bubarida TS-associated contigs consist of intron-containing genes homologous to sponge genes and feature GC percentage and coverage consistent with other eukaryotic sequences. We identified and characterized TS homologs from five different sponge species isolated from geographically distant locations, thereby suggesting a broad distribution amongst sponges. This work sheds light on the role of sponges in secondary metabolite production and speaks to the possibility that other sponge-specific molecules originate from the animal host.

Triterpene and Steroid Glycosides from Marine Sponges (Porifera, Demospongiae): Structures, Taxonomical Distribution, Biological Activities

“…However, the enzymes responsible for terpene biosynthesis were found recently in sponges but not in symbiotic microorganisms. Hence, these metabolites should be synthesized by sponges directly [ 8 ]. The distribution of different groups of secondary metabolites within the class Demospongiae of the phylum Porifera (sponges) was used for chemotaxonomy purposes.…”

Terpene synthases and pathways in animals: enzymology and structural evolution in the biosynthesis of volatile infochemicals

“…In addition to the finding of terpene cyclases in corals, another family of type I TPS genes has just been discovered in marine sponges of the order Bubarida. 169 The corresponding enzymes were shown to make intermediates in the biosynthesis of isonitrile sesquiterpenes but do not install the isonitrile group themselves. In contrast to coral TPSs, the sponge TPS genes do not apppear to be organized in gene clusters.…”

“…This is the first finding of TPSs that originate from sponge animal hosts independent from their microbial symbionts. 169…”

Function and Structure of a Terpene Synthase Encoded in a Giant Virus Genome

“…Such single-domain terpene synthases have previously been found in bacteria and fungi and in recent years in nonseed land plants, 16 red algae, 17 amoebae, 18 insects, 19,20 corals, 21,22 and sponges. 23 In contrast, class I terpene synthases from plants are known to be composed of two (α and β) or three (α, β, and γ) domains. 9−11 Additionally, the crystal structure suggests that OILTS exists as a monomer in solution, and the result of gel filtration chromatography also suggests it (Figure S17).…”