Simple Dipyrrin Analogues of Prodigiosin for Use as Colistin Adjuvants

Siwawannapong, Kittipan; Nemeth, Ansley M; Melander, Roberta J.; Rong, Jie; Davis, Joseph R.; Taniguchi, Masahiko; Carpenter, Morgan E; Lindsey, Jonathan S.; Melander, Christian

doi:10.1002/cmdc.202200286

Cited by 2 publications

(1 citation statement)

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“…Marine bacteria have significant potential as producing organisms of the tripyrrole prodiginines [ 71 ]. The prodiginines (represented by prodigiosin) demonstrate a breadth of biological activities, also including pronounced synergy with polymyxins against pathogenic Gram-negative bacteria [ 72 , 73 , 74 , 75 ].…”

Section: Do Marine Organisms Biosynthesize Exceptional Inhibitors Of ...mentioning

confidence: 99%

β-Lactams from the Ocean

Fisher

Mobashery

2023

Marine Drugs

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The title of this essay is as much a question as it is a statement. The discovery of the β-lactam antibiotics—including penicillins, cephalosporins, and carbapenems—as largely (if not exclusively) secondary metabolites of terrestrial fungi and bacteria, transformed modern medicine. The antibiotic β-lactams inactivate essential enzymes of bacterial cell-wall biosynthesis. Moreover, the ability of the β-lactams to function as enzyme inhibitors is of such great medical value, that inhibitors of the enzymes which degrade hydrolytically the β-lactams, the β-lactamases, have equal value. Given this privileged status for the β-lactam ring, it is therefore a disappointment that the exemplification of this ring in marine secondary metabolites is sparse. It may be that biologically active marine β-lactams are there, and simply have yet to be encountered. In this report, we posit a second explanation: that the value of the β-lactam to secure an ecological advantage in the marine environment might be compromised by its close structural similarity to the β-lactones of quorum sensing. The steric and reactivity similarities between the β-lactams and the β-lactones represent an outside-of-the-box opportunity for correlating new structures and new enzyme targets for the discovery of compelling biological activities.

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