**1. Introduction**

The genus *Streptomyces* are renowned as the largest contributor of currently used antibiotics [1]. Over the past decades, the most important classes of antimicrobial drugs have been isolated from this genus, such as tetracyclines, aminoglycosides, macrolides, and lypopeptides [2]. However, bioassay-guided screening of common actinomycetes, particularly the genus *Streptomyces*, often led to the rediscovery of known compounds and it is not an efficient approach to identifying new natural scaffolds [3]. Over the last decades, several dereplication strategies in natural product research were conducted to search for novel chemical structures from natural resources, such as bioactivity-guided fractionation, chemical profiles of crude extract collections and target compounds, and taxonomic identification of microbial strains [4]. Since terrestrial microbes have been well studied, several different approaches, including the investigation of unexploited habitats such as marine and extreme environments, have been employed to yield novel chemistry [5].

Polyketides are one of the largest classes of natural products isolated from the genus *Streptomyces* [6,7]. Among them, polycyclic aromatic polyketides, which are called "cytotoxic antibiotics", are one of the chemically richest classes of secondary metabolites and possess various biological activities, predominantly anticancer and antibacterial, and some of them are currently used as anti-cancer or anti-bacterial drugs, such as doxorubicin, epirubicin, and tetracycline [8–10]. The angucycline group is the largest group of type II PKS-engineered natural products, and is abundant in biological activities and chemical scaffolds [8], and the majority of angucycline producers were classified to be *Streptomycetes*

**Citation:** Anh, C.V.; Kwon, J.-H.; Kang, J.S.; Lee, H.-S.; Heo, C.-S.; Shin, H.J. New Angucycline Glycosides from a Marine-Derived Bacterium *Streptomyces ardesiacus*. *Int. J. Mol. Sci.* **2022**, *23*, 13779. https://doi.org/ 10.3390/ijms232213779

Academic Editors: Barbara De Filippis, Marialuigia Fantacuzzi and Alessandra Ammazzalorso

Received: 17 October 2022 Accepted: 3 November 2022 Published: 9 November 2022

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of various species [11]. Besides possessing an interesting cytotoxicity, some of the angucyclines act as hydroxylase and/or mono-oxygenase inhibitors, some potentially inhibit blood platelet aggregation and others demonstrate antibacterial or antiviral activity [11]. Therefore, angucyclines may serve as leading structures for new drug discovery.

As part of our ongoing studies on bioactive secondary metabolites isolated from marine-derived microorganisms, an actinomycetal strain was isolated near Nha Trang Bay, Vietnam, and identified as *Streptomyces ardesiacus* 156VN-095 by 16S rRNA gene sequence analysis. NMR and HPLC profiling of the ethyl acetate (EtOAc) extract from the culture broth of the strain showed characteristic signals of polycyclic aromatic polyketides. Chemical investigations of a large-scale culture of the strain were carried out and resulted in the isolation of three previously undescribed angucycline polyketides (**1**, **2**, and **9**) and their seven known congeners. Herein, we describe the isolation, structure elucidation, and their anti-Gram-positive bacterial and cytotoxic activities.
