Diverted Total Synthesis of Promysalin Analogs Demonstrates That an Iron-Binding Motif Is Responsible for Its Narrow-Spectrum Antibacterial Activity.
Promysalin is a species-specific Pseudomonad metabolite with unique bioactivity. To better understand the mode of action of this natural product, we synthesized 16 analogs utilizing diverted total synthesis (DTS). Our analog studies revealed that the bioactivity of promysalin is sensitive to changes within its hydrogen bond network whereby alteration has drastic biological consequences. The DTS library not only yielded three analogs that retained potency but also provided insights that resulted in the identification of a previously unknown ability of promysalin to bind iron. These findings coupled with previous observations hint at a complex multifaceted role of the natural product within the rhizosphere.
Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
Andrew D
AD
Steele
Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
Colleen E
CE
Keohane
Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
Kyle W
KW
Knouse
Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
Sean E
SE
Rossiter
Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
Sierra J
SJ
Williams
Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
William M
WM
Wuest
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products; D006860:Hydrogen Bonding; D007501:Iron / Q000737:chemistry*; D008968:Molecular Conformation; D011549:Pseudomonas / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012457:Salicylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017262:Siderophores / Q000737:chemistry; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D001688:Biological Products; D011759:Pyrrolidines; D012457:Salicylamides; D017262:Siderophores; C571083:promysalin; D007501:Iron