**1. Introduction**

Compared with terrestrial fungi, marine fungi are more abundant in species. Due to the complex environment, their metabolites have novel structures and diverse activities [1–4]. As an important member of marine microorganisms, fungi play an important role in the study of active natural products. Marine fungi can be obtained from marine animals, plants, sediments and seawater [5–8]. Therefore, marine fungi have a wide range of sources [6,9–15].

*Aspergillus* is a genus of fungi widely distributed in marine environments [16–18]. Common species include *A. fumigatus*, *A. niger*, *A. versicolor*, *A. flavus*, *A. ochraceu*, *A. ticus*, *A. terreus*, etc. Marine *Aspergillus* is an important resource in the production of active natural products, such as steroids, flavonoids, azolones, etc. [7,19–22]. These metabolites are structurally diverse and exhibit a wide range of biological activities, including anticancer, antiviral, antibacterial, anti-inflammatory, lipid-lowering and anti-diabetic [22–27].

Due to the wide range of *Aspergillus* sources, the diverse secondary metabolites and the wide biological activities, the research on *Aspergillus* metabolites has attracted much attention. Therefore, a series of excellent reviews on this subject have been published so far [28–39]. In 2016, Fouillaud et al. reviewed the knowledge of anthraquinones and their derivatives derived from filamentous fungi [40]. In 2022, Hafez Ghoran et al. updated this study and summarized and classified the structures and activities of 296 anthraquinones and their derivatives [41]. In 2019, Youssef et al. reviewed the chemical and biological activities of peptides which isolated and identified from marine fungi [22]. 131 peptides were reported from these 17 genera, and about 53% of the isolated peptides showed cytotoxic, antibacterial and antiviral activities. In 2020, Jiang et al. reviewed the chemical structure and bioactive properties of new terpenes from marine derived fungi, as well as the biodiversity of these fungi from 2015 to 2019 [19]. *Penicillium*, *Aspergillus* and *Trichoderma* fungi were the main producers of terpenes. In 2021, Rani et al. reviewed the research status of microbial antibacterial molecules [10]. In 2022, Li et al., reviewed the chemistry and bioactivity of marine-derived bisabolane sesquiterpenoids [1]. In 2013, Lee et al. reviewed the bioactive secondary metabolites of *Aspergillus* derived from marine sources [42]. In 2018, Wang et al. reviewed 232 new bioactive metabolites from *Aspergillus* of marine origin

**Citation:** Li, H.; Fu, Y.; Song, F. Marine *Aspergillus*: A Treasure Trove of Antimicrobial Compounds. *Mar. Drugs* **2023**, *21*, 277. https:// doi.org/10.3390/md21050277

Academic Editor: Dehai Li

Received: 31 March 2023 Revised: 22 April 2023 Accepted: 25 April 2023 Published: 28 April 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

from 2006 to 2016 and classified their bioactivity and chemical structures [43]. In 2020, Xu et al. reviewed the structural diversity and biological activity of 130 heterocyclic alkaloids produced by *Aspergillus* of marine origin from early 2014 to late 2018 [44]. However, there have been no studies on the antimicrobial compounds from marine *Aspergillus* in the last two years despite the fact that over the past two years, reports of antibacterial metabolites from *Aspergillus* have increased [45–51]. It is believed that the study of *Aspergillus* living in marine environments will facilitate the isolation of new fungal species and lead to the discovery of new compounds. Therefore, this review updates current compounds to cover metabolites isolated from marine *Aspergillus* between January 2021 and March 2023. It also provides structural diversity of compounds, as well as detailed information on sources and associated antimicrobial activity. We introduced the structural diversity and antimicrobial activity of 98 compounds isolated from marine-derived *Aspergillus*. This study will contribute to a better understanding of the chemical properties and biological activities of natural products from marine *Aspergillus*, thus facilitating drug discovery and development.

#### **2.** *Aspergillus* **sp. from Various Marine Sources and Their Antimicrobial Activities**

#### *2.1. Aspergillus sp. from Marine Animals and Their Antimicrobial Activities*

Trypacidin (**1**) was isolated from the *A. fumigatus* HX-1 associated with clams (Figure 1). The anti-*Vibrio harveyi* activity of trypacidin was the same as that of streptomycin sulfate, and the minimum inhibitory concentration (MIC) was 31.25 μg/mL [52].

**Figure 1.** Compounds of *Aspergillus* sp. derived from marine animals.

Two new dipeptides, asperopiperazines A and B (**2** and **3**), were obtained from *Aspergillus* sp. DY001 (Figure 1). The MICs of asperopiperazines A and B against *Escherichia coli* were 8 and 4 μM, and 8 and 8 μM against *S. aureus*, respectively [53].

In conclusion, only two *Aspergillus* species producing antimicrobial compounds are found from marine animals (except sponges and corals). Three compounds from these two *Aspergillus* strains have been reviewed for their antimicrobial activities. Notably, asperopiperazines A and B from *Aspergillus* sp. DY001 showed potent antimicrobial activities against *E. coli* and *S. aureus*.
