Macrolactins: biological activity and biosynthesis

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, anti-inflammatory, 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: Biological activities; Biosynthesis; Macrolactins; Structural diversity.

Fig. 1

Chemical structures of previously identified MLNs (1–33) (Chakraborty et al. , ; Gustafson et al. ; Jaruchoktaweechai et al. ; Ji et al. ; Lu et al. ; Mohamad et al. ; Mondol et al. ; Muhammad and Hee ; Nagao et al. ; Schneider et al. ; Tareq et al. ; Xue et al. ; Yan et al. ; Yoo et al. ; Zheng et al. 2007)

Fig. 2

Chemical structures of new natural MLNs since 2014 (34–39) (Chakraborty et al. ; Chakraborty et al. ; Li et al. ; Mondol et al. ; Muhammad and Hee ; Yan et al. 2016)

Fig. 3

The proposed biosynthetic pathway of MLNs. (Liu et al. ; Qin et al. ; Schneider et al. 2007) KS ketosynthase, ACP acyl carrier protein, AT acyltransferase, KR ketoreductase, DH dehydratase, ER enoylreductase, TE thioesterase, GT glycosyltransferase. bmmGT1 is located outside of the MLN biosynthetic gene cluster

Fig. 4

Generation of “unnatural” new MLNs (40–50). a Generation of compounds 40–46 by BmmGT1; b generation of compounds 47–50 by BmmGT2 (Liu et al. ; Liu et al. ; Qin et al. 2014)