Bacterial Alkaloids Prevent Amoebal Predation

Abstract

Bacterial defense mechanisms have evolved to protect bacteria against predation by nematodes, predatory bacteria, or amoebae. We identified novel bacterial alkaloids (pyreudiones A-D) that protect the producer, Pseudomonas fluorescens HKI0770, against amoebal predation. Isolation, structure elucidation, total synthesis, and a proposed biosynthetic pathway for these structures are presented. The generation of P. fluorescens gene-deletion mutants unable to produce pyreudiones rendered the bacterium edible to a variety of soil-dwelling amoebae.

Natural Products from Social Amoebae

“…The co‐evolution of bacteria and amoebae has led to the emergence of both bacterial defense mechanisms against their predators as well as symbiotic interactions . The secretion of amoebicidal secondary metabolites, for instance, is an efficient strategy for bacteria to kill or deter their predator . This renders amoeba‐bacteria interactions a particularly promising source for the discovery of novel bioactive natural products.…”

“…[64] The secretion of amoebicidal secondary metabolites, for instance, is an efficient strategyf or bacteria to kill or deter their predator. [65] This renders amoeba-bacteria interactions ap articularly promising source for the discovery of novel bioactive natural products. Hence, we can expect aw ealth of new molecules emerging from detailed investigations of this fascinating microbial interplay.…”

Bioinspired Synthesis of (−)‐PF‐1018

“…Acetylation and conversion into the Weinreb amide gave 24 . A subsequent Dieckmann condensation then afforded an unstable pyrrolizidine dione, which was coupled with diethyl phosphonoacetic acid to afford the tetramic acid phosphonate 25 . This building block was also condensed with octanal to afford the recently isolated anionic lipid pyreudione C …”

“…Future work will be directed towards exploring the biosynthesis, biological activity, and structure-activity relationships of PF-1018 and other anionic lipids that feature proline-derived tetramic acids, such as talarotoxin [41] and the pyreudiones. [10,20,42]…”

“…A subsequent Dieckmann condensation then afforded an unstable pyrrolizidine dione, [20] which was coupled with diethyl phosphonoacetic acid to afford the tetramic acid phosphonate 25. [19,21] This building block was also condensed with octanal to afford the recently isolated anionic lipid pyreudione C. [20,22] The key step of our synthesis warrants further analysis. Given the many possible isomers that can be formed, we consider this a remarkable result both in terms of selectivity and yield (see the Supporting Information, Figure S1).…”