Complex microbiome underlying secondary and primary metabolism in the tunicate- Prochloron symbiosis

Abstract

The relationship between tunicates and the uncultivated cyanobacterium Prochloron didemni has long provided a model symbiosis. P. didemni is required for survival of animals such as Lissoclinum patella and also makes secondary metabolites of pharmaceutical interest. Here, we present the metagenomes, chemistry, and microbiomes of four related L. patella tunicate samples from a wide geographical range of the tropical Pacific. The remarkably similar P. didemni genomes are the most complex so far assembled from uncultivated organisms. Although P. didemni has not been stably cultivated and comprises a single strain in each sample, a complete set of metabolic genes indicates that the bacteria are likely capable of reproducing outside the host. The sequences reveal notable peculiarities of the photosynthetic apparatus and explain the basis of nutrient exchange underlying the symbiosis. P. didemni likely profoundly influences the lipid composition of the animals by synthesizing sterols and an unusual lipid with biofuel potential. In addition, L. patella also harbors a great variety of other bacterial groups that contribute nutritional and secondary metabolic products to the symbiosis. These bacteria possess an enormous genetic potential to synthesize new secondary metabolites. For example, an antitumor candidate molecule, patellazole, is not encoded in the genome of Prochloron and was linked to other bacteria from the microbiome. This study unveils the complex L. patella microbiome and its impact on primary and secondary metabolism, revealing a remarkable versatility in creating and exchanging small molecules.ascidian | metagenomics | photosynthesis | natural products

Species specificity of symbiosis and secondary metabolism in ascidians

“…Beyond defense, symbiotic metabolites in ascidians are also known to have other roles. For example, mycosporine amino acids are critical to the defense of tropical ascidians against ultraviolet irradiation, but they are produced by symbiotic bacteria Donia et al, 2011a). Thus, symbiotic bacteria contribute critical secondary metabolites that are apparently necessary for the survival of the animals.…”

“…symbiotic bacteria produce a variety of toxic, cyclic peptides known as cyanobactins (Donia et al, 2008), as well as ultraviolet-protectant mycosporine amino acids (Donia et al, 2011a). Prochloron seems to be obligate for the host animals, yet horizontal transmission dominates for this group (Hirose and Fukuda, 2006;Hirose et al, 2009;Kojima and Hirose, 2010).…”

Genome streamlining and chemical defense in a coral reef symbiosis

“…Like other tunicates, L. patella is a rich source of potentially bioactive drugs and drug leads (11), which in a few cases are known to be produced by symbiotic bacteria (7,8). Beyond the major symbiont, the cyanobacterium Prochloron didemni, L. patella harbors a complex microbiome (12). Some L. patella samples contain highly potent cytotoxic polyketides, patellazoles (13-15) (IC 50 332 pM, KB cells; Fig.…”

The International Conference of Natural Product Biosynthesis (ICNPB, 8th US–Japan seminar on the Biosynthesis of Natural Products)

“…To find the patellazole biosynthetic gene cluster from uncultured bacteria, the whole genome of the host and symbiont were sequenced. 17 Engineering the patellin biosynthetic pathway in E. coli to produce novel peptide molecules was also discussed. 18 Dr Toshiyuki Wakimoto (University of Tokyo) described identification of the calyculin biosynthetic gene cluster from the marine sponge Discodermia calyx.…”