Parallel lives of symbionts and hosts: chemical mutualism in marine animals

Abstract

Covering: up to 2018 Symbiotic microbes interact with animals, often by producing natural products (specialized metabolites; secondary metabolites) that exert a biological role. A major goal is to determine which microbes produce biologically important compounds, a deceptively challenging task that often rests on correlative results, rather than hypothesis testing. Here, we examine the challenges and successes from the perspective of marine animal-bacterial mutualisms. These animals have historically provided a useful model because of their technical accessibility. By comparing biological systems, we suggest a common framework for establishing chemical interactions between animals and microbes.

Figure 1

Defensive natural products isolated from marine animals.

Figure 2. Functional evidence for ET-743 biosynthesis

Saframycin A (9) is a bacterial compound shown to be made via an NRPS module SfmC2. Feeding precursor 10 to apo-SfmC2 enabled the reductase to function, affording 11, while the holo protein was able to fully incorporate 10 into the tetrahydroquinoline core, e.g. 12. The same analog 10 was used with putative ET-743 reductive domain EtuA2(RE) from the tunicate metagenome, although 10 is not identical to the putative precursor for 8; 10 was reduced to 11.

Figure 3. Functional evidence for bromophenyl ether biosynthesis

Natural sponge compounds 13 and 14 could be made from synthetic precursor 15 using expressed genes bmp7 and bmp7–12, respectively. These genes were identified from symbiotic cyanobacteria living in a sponge.

Figure 4. Functional evidence for cyanobactin production

Natural products 16 and 17, first isolated from a tunicate, could be produced in E. coli using the patellamide and trunkamide biosynthetic pathways. These pathways are nearly identical (green: 100% identity). The major differences (red: >60% identity) mostly reflect regions where genes or domains with new functions have been imported. For example, the large red block at left reflects a change in chemoselectivity of the heterocyclase. The precursor peptides for each compound are shown, each containing two core peptides shown in black. The core peptide encoding the natural products are shown in bold.

Figure 5

An antibacterial natural product isolated from a shipworm.

Figure 6

Natural products originally isolated from Theonella swinhoei. Onnamide A (23) is shown with the structurally-related natural product, pederin (22).

Figure 7

Natural products from the genus Discodermia.

Figure 8

The structures of patellazole A (27), mandelalide A (28), tetrodotoxin (29), and nocapyrone H (30).

Scheme 1

Biosynthesis of shinorine (1). The shinorine gene cluster from Anabaena variabilis and the enzymatic route from sedoheptulose 7-phosphate (3) to shinorine (1).