Macrolactins: biological activity and biosynthesis
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REVIEW
Macrolactins: biological activity and biosynthesis Ting Wu1 · Fei Xiao1 · Wenli Li1,2 Received: 23 June 2020 / Accepted: 3 August 2020 © Ocean University of China 2020
Abstract Marine microorganisms have proven to be a rich source of natural products with unique structures and novel activities, due to their special living conditions. Macrolactins (MLNs), mostly produced by marine-derived microorganisms, are a group of 24-membered lactone natural products, which exhibit potent antibacterial, antifungal, antiviral, anticancer, antiinflammatory, anti-angiogenic and other activities. Their extensive biological activities make them potential compounds for drug development. MLNs are biosynthesized via a type I polyketide synthase (PKS) pathway with different tailoring steps, such as epoxidation, glycosylation and acylation. These modification steps provide opportunities to diversify their structures by combinatorial biosynthesis strategies. This review mainly focuses on the newly discovered MLNs in the past five years, including their biological activities and relevant biosynthetic studies. Keywords Macrolactins · Biological activities · Biosynthesis · Structural diversity
Introduction The ocean covers more than 70% of the earth’s surface and hosts a considerable diversity of microorganisms, which could produce natural products with unique structures and novel activities (Jiménez 2018). Marine natural products play an important and promising role in biomedical research and drug development (Wang et al. 2017). Macrolactins (MLNs) represent a group of unique structural patterns containing a 24-membered lactone ring, which were mainly isolated from marine bacteria. Since macrolactins A-F (MLN A-F) were first isolated in 1989 (Gustafson et al. 1989), more than 33 MLNs have been reported (compounds 1–33, Fig. 1). The main structural differences include the position and numbers of olefinic bonds in the lactone ring Edited by Chengchao Chen. * Fei Xiao [email protected] * Wenli Li [email protected] 1
2
Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China
and the diverse types of post-modification groups. MLNs exhibit a wide range of pharmacological activities, including antibacterial (Nagao et al. 2001), antiviral (Gustafson et al. 1989), anticancer (Jin et al. 2017a), anti-inflammatory (Yan et al. 2016) and anti-angiogenic activities (Ji et al. 2012) (Table 1). Of note, MLN A (1) and 7-O-succinyl macrolactin A (SMA, 7) are currently in preclinical evaluation as antimacular degeneration and antitumor agents (Ji et al. 2010, 2012; Jin et al. 2017a, b; Jung et al. 2014). Due to their various chemical structures and potent biological activities, MLNs are promising lead compounds for drug discovery (Wang et al. 2014). The backbone of MLNs is assembled by an AT-less polyketide synthase
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