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, 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.

Evaluation of the Marine Bacterial Population in the Great Bitter Lake, Egypt, as a Source of Antimicrobial Secondary Metabolites

“…They are biosynthesized through the PKS-I system. Many bioactivities were reported regarding macrolactins including, antibacterial, antifungal, antiviral, anticancer, anti-inflammatory, anti-angiogenic, and other activities [62]. Macrolactin N produced by B. subtilis was reported for its antimicrobial activity against S. aureus and E. coli as it inhibits the peptide deformylase enzyme [38].…”

Marine natural products

“…Whilst summarising each individual review is beyond the scope of this review, a snapshot of 17 standout articles is given below. Review highlights included those describing advances in phenazine chemistry over the past decade, 81 a catalogue of 1062 terpenoid NPs produced by bacteria, entitled "Bacterial terpenome", 82 overviews of the biology and chemistry of macrolactins 83 and thiopeptides, 84 how the recording and mining of MS data is transforming NP research, 85 N-N bond formation reactions involved in NP biosynthesis, 86 developing techniques that can be applied to single cells for accelerating microbial NP research, 87 recent highlights of biosynthetic studies on marine bacteria products, 88 a summary detailing 127 halogenated compounds identied from marine actinomycetes (1992-2022), 89 use of synthetic biology to elucidate NP BGCs encoded in Streptomyces genomes, 90 chemical labelling strategies for NP detection and isolation, 91 cryptic halogenation reactions associated with NP biosynthesis, 92 volatile nitrogenous compounds from bacteria, 93 the versatile role of condensation domains in NP biosynthesis, 94 importance of microbial NP databases and their impact in the multi-omics era, 95 diversity, mechanism and selectivity of polyketide b-branching, 96 and an overview of natural antiplasmodial lead compounds (648 NPs from various natural sources; 2013-2019). 97 Other marine bacterial research that made noteworthy contributions to the eld included the enhanced production (3.8-fold increase) of the cytotoxic and antibacterial compound ohmyungsamycin A that was achieved via adenylation domain engineering and optimisation of culture conditions, 98 the semisynthesis of 18 ilamycin F derivatives, several of which had improved anti-tubercular activity compared to the MNP, 99 research on the biosynthesis of anthraquinone-fused enediynes (e.g.…”

Chemical and biological diversity of new natural products from marine sponges: a review (2009–2018)

“…Although the number of bioactive alkaloids and terpenoids was the largest, the highest proportion of bioactives belonged to macrolides with 84.0% followed by peptides with 64.3%. Two recent reviews summarized marine-derived macrolides with therapeutic potential, which displayed a wide range of bioactivities including cytotoxic, antifungal, antiviral, antibacterial, antimitotic, and other activities (Wu et al 2021b ; Zhang et al 2021 ). Peptides were promising drug candidates due to their reduced size, stability, low immunogenicity, and diversity of bioactivities including anti-proliferative, antiviral, anti-coagulant, antioxidant, antiobesity, antidiabetic, anti-hypertensive, and calcium-binding activities (Gogineni and Hamann 2018 ; Hu et al 2015 ).…”