Possible Functional Roles of Patellamides in the Ascidian-Prochloron Symbiosis

Abstract

Patellamides are highly bioactive compounds found along with other cyanobactins in the symbiosis between didemnid ascidians and the enigmatic cyanobacterium Prochloron. The biosynthetic pathway of patellamide synthesis is well understood, the relevant operons have been identified in the Prochloron genome and genes involved in patellamide synthesis are among the most highly transcribed cyanobacterial genes in hospite. However, a more detailed study of the in vivo dynamics of patellamides and their function in the ascidian-Prochloron symbiosis is complicated by the fact that Prochloron remains uncultivated despite numerous attempts since its discovery in 1975. A major challenge is to account for the highly dynamic microenvironmental conditions experienced by Prochloron in hospite, where light-dark cycles drive rapid shifts between hyperoxia and anoxia as well as pH variations from pH ~6 to ~10. Recently, work on patellamide analogues has pointed out a range of different catalytic functions of patellamide that could prove essential for the ascidian-Prochloron symbiosis and could be modulated by the strong microenvironmental dynamics. Here, we review fundamental properties of patellamides and their occurrence and dynamics in vitro and in vivo. We discuss possible functions of patellamides in the ascidian-Prochloron symbiosis and identify important knowledge gaps and needs for further experimental studies.

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

“…Such biochemical insights can be applied to the rationally engineered creation of large libraries of synthetic compounds for lead compound identification [ 42 ]. The ecological roles of these symbiont-derived cyanobactins have been proposed, including metal ion sequestration and/or transport, chemical defense and catalysis and/or transport of substrates [ 43 ]. Along with P. didemni , the tunicate host also houses a novel symbiotic α-proteobacterium, Ca.…”

Efficient Synthesis for a Wide Variety of Patellamide Derivatives and Phosphatase Activity of Copper‐Patellamide Complexes

“…The true biological function of these interesting macrocycles and their metal complexes, however, is not yet known. [5,6] A recent study has shown, that fluorescencelabeled patellamide analogues bind copper(II) ions in vivo, [4] and this, together with the known complex stabilities (specifically Cu II vs. Zn II ) and the observed accumulation of Cu II in ascidians (approx. 10 4 -fold vs. the surrounding seawater), supports the general assumption that the copper(II) coordination chemistry of patellamides is of biological relevance.…”

“…The complexes have shown the ability to catalyze a wide range of reactions of potential metabolic relevance, such as carbonic anhydrase, phosphatase, β‐lactamase and glucosidase. The true biological function of these interesting macrocycles and their metal complexes, however, is not yet known [5,6] . A recent study has shown, that fluorescence‐labeled patellamide analogues bind copper(II) ions in vivo, [4] and this, together with the known complex stabilities (specifically Cu II vs. Zn II ) and the observed accumulation of Cu II in ascidians (approx.…”

“…10 4 -fold vs. the surrounding seawater), supports the general assumption that the copper(II) coordination chemistry of patellamides is of biological relevance. [3,6,7] The class of peptides referred to as patellamides are cyclic octapeptides, in which four of the peptide bonds have enzymatically been heterocyclized to thiazole or oxazoline (derived from cysteine and serine or threonine, respectively; see Scheme 1 for structures of patellamide derivatives). So far, patellamide derivatives have only been found in ascidians of the species Lissoclinum patella, where they are produced in vast amounts of up to several percent of the organism's dry mass.…”

A Dicopper(II)‐Based Carbonic Anhydrase Model—Quantum‐Chemical Evaluation of the Mechanistic Pathway

“…A number of key metabolites of the prokaryote Prochloron didemni, a photosynthetic symbiont of the sea squirt Lissoclinum patella, cyclic pseudo-octapeptides such as ascidiacyclamide, patellamides AÀ G and ulicyclamide are expressed via the ribosomal RiPP pathway and are known to be of medicinal interest. [1][2][3][4][5][6][7] These natural products and especially their Cu II chemistry have gained the interest of coordination chemists, [1,3] also because the Cu II concentration in their ascidian host is about two orders of magnitude higher than in the surrounding sea water. [8] The biosynthesis of the azole/azoline-based cyclic peptides is known and biochemical in vitro methods for their production have been developed.…”