Orfamide-A-mediated bacterial-algal interactions involve specific Ca²⁺ signalling pathways

Abstract

The antagonistic bacterium Pseudomonas protegens secretes the cyclic lipopeptide orfamide A, which triggers a Ca2+ signal, causing the deflagellation of the green microalga Chlamydomonas reinhardtii. By investigating targeted synthetic orfamide A variants and inhibitors, we found that at least two Ca2+-signalling pathways and TRP channels are involved in this response.

Total Synthesis and Structure Correction of the Cyclic Lipodepsipeptide Orfamide A

“…Beyond biological identity, these data indicate that its stereochemistry profoundly affects the biological properties of orfamide A. This is corroborated by other biological activities and the activity of further orfamide A variants [31] …”

“…This is corroborated by other biological activities and the activity of further orfamide A variants. [31] Since orfamide A causes immobilization in several flagellated chlorophyte algae, [9] we also studied the medically relevant Trypanosoma brucei, a flagellated parasitic microorganism that causes African sleeping sickness. While orfamide A (3) did not cause deflagellation of T. brucei, it nonetheless inhibited its growth (IC 50 = 6 μM, see Supporting Information for details), as it did in C. reinhardtii.…”

An NMR fingerprint matching approach for the identification and structural re-evaluation ofPseudomonaslipopeptides

“…As a result, in this case, configurational variability within one NRPS assembly line can be invalidated, and a revision is required for the configuration of Pf-5 based orfamides as shown in Table 2. Gratifyingly, this outcome was recently also arrived at using a completely independent approach involving total synthesis of orfamide A by Bando et al (personal communication), whereby the original stereochemistry led to loss of green algal deflagellation activity, while the corrected one was as active as the natural compound (68). Finally, we could establish that the orfamide produced by Pseudomonas sp.…”

“…Gratifyingly, this outcome was recently also arrived at using a completely independent approach involving total synthesis of orfamide A by Bando et al ( personal communication ), whereby the original stereochemistry led to loss of green algal deflagellation activity, while the corrected one was as active as the natural compound (68). Finally, we could establish that the orfamide produced by Pseudomonas sp.…”

An Nuclear Magnetic Resonance Fingerprint Matching Approach for the Identification and Structural Re-Evaluation of Pseudomonas Lipopeptides

“…As a result, in this case, configurational variability within one NRPS assembly line can be invalidated, and a revision is required for the configuration of Pf-5 based orfamides as shown in Table 2 . Gratifyingly, this outcome was recently also arrived at using a completely independent approach involving total synthesis of orfamide A by Bando et al ( 69 ), whereby the original stereochemistry led to loss of green algal deflagellation activity, while the corrected one was as active as the natural compound ( 70 ). Finally, we could establish that the orfamide produced by Pseudomonas sp.…”