**1. Introduction**

Structurally diverse nitrogen-containing heterocycles, such as pyrroles, imidazoles, oxazoles, pyridines, and quinolones, are widely distributed in marine organisms and microorganisms. These naturally occurring secondary metabolites often exhibit significant pharmacological activities, including antibacterial, antifungal, antiparasitic, and anticancer activities [1–6]. Furthermore, these compounds are often amenable to further structural modifications [7–10]. Currently, marine-derived imidazole alkaloids are reported mainly to be isolated from sponges, while reports of marine bacteria as bioresource are relatively rare [2,6,11–14].

As a member of the family *Flavobacteriaceae* within the phylum *Bacteroidetes*, isolates of the genus *Tenacibaculum* have been mainly obtained from marine environments, such as sea water, tidal flat, and aquaculture systems, as well as marine organisms like bryozoan, sea anemone, oyster, sponge and green algae [15–22]. Bacteria of this genus are the etiological agen<sup>t</sup> of an ulcerative disease known as tenacibaculosis, which affects a large number of marine fish species in the world [23]. Up to now, the natural products isolated from *Tenacibaculum* strains comprise only siderophores that showed beside their chelating activity also cytotoxicity [24–26], and phenethylamine-containing heterocycles. The latter include two imidazole alkaloids identified in our previous search for antimicrobial metabolites from marine flavobacteria. It was shown that they could be synthesized by decarboxylation of phenylalanine, catalyzed by the enzyme DisA [27]. Likewise, the tryptamine and phenethylamine moieties of imidazole alkaloids isolated from a marine sponge-associated *Bacillus* strain were proposed to be formed by an aromatic amino acid

**Citation:** Wang, L.; Marner, M.; Mettal, U.; Liu, Y.; Schäberle, T.F. Seven New Alkaloids Isolated from Marine Flavobacterium *Tenacibaculum discolor* sv11. *Mar. Drugs* **2022**, *20*, 620. https://doi.org/10.3390/ md20100620

Academic Editor: Asunción Barbero

Received: 4 September 2022 Accepted: 28 September 2022 Published: 30 September 2022

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decarboxylase-dependent reaction [28]. In order to further expand the array of available nitrogen-containing heterocycles, the metabolome of *T. discolor* sv11 was further investigated. Herein, we present the isolation, structure elucidation and biological activity of new alkaloids from the bacterium, and link the enzymatic activity of DisA to their biosynthesis using both, in vivo and in vitro assays.
