Discovery, Yield Improvement, and Application in Marine Coatings of Potent Antifouling Compounds Albofungins Targeting Multiple Fouling Organisms.

Marine biofouling caused huge economic losses of maritime industries. We aim to develop high-efficient, less-toxic, and cost-effective antifoulants to solve the problems of biofouling. In this study, we described the antifouling compounds albofungin and its derivatives (albofungin A, chrestoxanthone A, and chloroalbofungin) isolated from the metabolites of bacterium Streptomyces chrestomyceticus BCC 24770, the construction of high-yield strains for albofungin production, and application of albofungin-based antifouling coatings. Results showed that these albofungins have potent antibiofilm activities against Gram-positive and Gram-negative bacteria and anti-macrofouling activities against larval settlement of major fouling organisms with low cytotoxicity. With the best antifouling activity and highest yield in bacterial culture, albofungin was subsequently incorporated with hydrolyzable and degradable copolymer to form antifouling coatings, which altered biofilm structures and prevented the settlement of macrofouling organisms in marine environments. Our results suggested that albofungins were promising antifouling compounds with potential application in marine environments.

Bathiapeptides: Polythiazole-Containing Peptides from a Marine Biofilm-Derived Bacillus sp.

Bacteria in marine biofilms are a rich reservoir of natural products. To facilitate novel secondary metabolite discovery, we investigated the metabolic profile of a marine biofilm-derived Bacillus sp. B19-2 by combining bioinformatics and LC-UV-MS analyses. After dereplication and purification of putatively unknown compounds, a new family of compounds 1-8 was uncovered and named bathiapeptides. Structural elucidation using NMR, HRESIMS, ozonolysis, advanced Marfey's analysis, and X-ray diffraction revealed that bathiapeptides are polypeptides that contain a rare polythiazole moiety. These compounds exhibited strong cytotoxicity against Hep G2, HeLa, MCF-7, and MGC-803 cell lines, and the lowest IC50 value was 0.5 µM. An iterative biosynthesis logic in bathiapeptides' biosynthesis was proposed based on the identified chemical structures and putative gene cluster analysis.

Isolation, Genomic and Metabolomic Characterization of Streptomyces tendae VITAKN with Quorum Sensing Inhibitory Activity from Southern India.

Streptomyces are among the most promising genera in terms of production ability to biosynthesize a variety of bioactive secondary metabolites with pharmaceutical interest. Coinciding with the increase in genomic sequencing of these bacteria, mining of their genomes for biosynthetic gene clusters (BGCs) has become a routine component of natural product discovery. Herein, we describe the isolation and characterization of a Streptomyces tendae VITAKN with quorum sensing inhibitory (QSI) activity that was isolated from southern coastal part of India. The nearly complete genome consists of 8,621,231bp with a GC content of 72.2%. Sequence similarity networks of the BGCs detected from this strain against the Minimum Information about a Biosynthetic Gene Cluster (MIBiG) database and 3365 BGCs predicted by antiSMASH analysis of publicly available complete Streptomyces genomes were generated through the BiG-SCAPE-CORASON platform to evaluate its biosynthetic novelty. Crude extract analysis using high-performance liquid chromatography connected to high resolution tandem mass spectrometry (HPLC-HRMS/MS) and dereplication through the Global Natural Product Social Molecular Networking (GNPS) online workflow resulted in the identification of cyclic dipeptides (2, 5-diketopiperazines, DKPs) in the extract, which are known to possess QSI activity. Our results highlight the potential of genome mining coupled with LC-HRMS/MS and in silico tools (GNPS) as a valid approach for the discovery of novel QSI lead compounds. This study also provides the biosynthetic diversity of BGCs and an assessment of the predicted chemical space yet to be discovered.