It is well known that microorganisms are abundant in sponges, which make up 50%-60% of the host biomass. Moreover, mounting evidence suggests that bacteria, fungi, and cyanobacteria, all associated with sponges, are the true creators of the bioactive compounds identified from sponges. The discovery of 774 structurally active compounds from 1998 to 2017 presents a good overview of natural product resources in sponge-associated microorganisms. During the last 5 years, many new molecules, including peptides, polyketides, alkaloids, and terpenes, have been identified from sponge-associated microorganisms through various mining strategies, exhibiting a wide range of biological activities, such as anti-microbial, anti-cancer, enzyme inhibition, and antioxidant properties. In this paper, 140 compounds produced by sponge-associated microorganisms from 2017 to 2022 are systematically discussed in terms of their structures, biological activities, and strain sources, as well as the mining strategies, which not only further updates the natural product library of sponge-associated microorganisms but also provides a new guideline for exploring the “dark matter” in sponges.

Hahella is one characteristic genus under the Hahellaceae family and shows a good potential for synthesizing new natural products. In this study, we examined the distribution of the secondary metabolite biosynthetic gene cluster (SMBGC) under Hahella with anti-SMASH. The results derived from five genomes released 70 SMBGCs. On average, each strain contains 12 gene clusters, and the most abundant ones (45.7%) are from the family of non-ribosomal peptide synthetase (NRPS) and non-ribosomal peptide synthetase hybrid with polyketide synthase (NRPS/PKS), indicating a great potential to find bioactive compounds. The comparison of SMBGC between H. chejuensis and other species showed that H. chejuensis contained two times more gene clusters than H. ganghwensis. One strain, designed as NBU794, was isolated from the mangrove soil of Dongzhai Port in Haikou (China) by iChip. The 16S rRNA gene of NBU794 exhibited 99% identity to H. chejuensis KCTC 2396 and clustered with the H. chejuensis clade on the phylogenetic trees. Genome mining on strain NBU794 released 17 SMBGCs and two groups of bioactive compounds, which are chejuenolide A-C and nine prodiginines derivatives. The prodiginines derivatives include the well-known lead compound prodigiosin and two new compounds, 2-methyl-3-pentyl-4-O-methyl-prodiginine and 2-methyl-3-octyl-prodiginine, which were identified through fragmentation analysis based on LC-MS/MS. The anti-microbial activity assay showed prodigiosin and 2-methyl-3-heptyl-prodiginine exhibited the best performance in inhibiting Escherichia coli, Salmonella paratyphi B, MASA Staphylococcus aureus, Bacillus subtilis, and Candida albicans. Moreover, the yield of prodigiosin in H. chejuensis NBU794 was also evaluated, which could reach 1.40 g/L under the non-optimized condition and increase to 5.83 g/L in the modified ISP4 medium with macroporous adsorption beads added, indicating that NBU794 is a promising source of prodigiosin.

Background: In the present research, challenges arose when many reports have been published on the poisoning of humans due to the ingestion of crops of Crataegus plants contaminated with cyanobacterial toxins. The discovery of several poisonings around agricultural zones prompted us to study the toxic compounds in a strain of Neowestiellopsis which is the most abundant in the agricultural zones of Kermanshah province of Iran, using a polyphasic approach. Molecular procedure was followed to study these strains deeply. Material and methods: To elucidate their systematic position, besides the 16S rRNA gene, the analyses of molecular toxicity markers, namely nos, mcy G, mcy D and internal transcribed spacer (ITS), were also used. Results: Based on the results, for the first time, we record the presence of a gene cluster coding for the biosynthesis of a bioactive compound (Nostopeptolides) that is very rare in this family and the presence of toxic compounds (microcystin), which might account for the poisoning of humans. Conclusions: This case is the first observation of a toxic soil strain from the genus Neowestiellopsis from agricultural fields in Iran.