Aquimarins, Peptide Antibiotics with Amino-Modified C-Termini from a Sponge-Derived Aquimarina sp. Bacterium


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Date

2022-02-14

Publication Type

Journal Article

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yes

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Abstract

Genome mining and bioactivity studies suggested the sponge-derived bacterium Aquimarina sp. Aq135 as a producer of new antibiotics. Activity-guided isolation identified antibacterial peptides, named aquimarins, featuring a new scaffold with an unusual C-terminal amino group and chlorine moieties. Responsible for the halogenation is the Fe(II)/α-ketoglutarate-dependent chlorinase AqmA that halogenates up to two isoleucine residues in a carrier protein-dependent fashion. Total syntheses of two natural aquimarins and eight non-natural variants were developed. Structure-activity relationship (SAR) studies with these compounds showed that the synthetically more laborious chlorinations are not required for antibacterial activity but enhance cytotoxicity. In contrast, variants lacking the C-terminal amine were virtually inactive, suggesting diamines similar to the terminal aquimarine residue as candidate building blocks for new peptidomimetic antibiotics.

Publication status

published

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Volume

61 (8)

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Publisher

Wiley-VCH

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Subject

Antibiotics; Bacteria; Natural products; Nonribosomal peptides; Sponges

Organisational unit

03980 - Piel, Jörn / Piel, Jörn check_circle
03625 - Oxenius, Annette / Oxenius, Annette check_circle

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