Discovery of New Secondary Metabolites from Marine Bacteria Hahella Based on an Omics Strategy

Abstract

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 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.

Embracing the Imperfectness of Nature using Highly Reactive N-Acyl Azahexatrienes

“…After accomplishing the syntheses of all reported chejuenolides, Liu and co-workers also identified these three natural products from a newly discovered H. chejuensis strain, NBU794, by applying genome mining and metabolomics. 23 Similar to the original isolation protocol, 13 the relative abundance of chejuenolide C in the fermented extracts was remarkably lower than the other two congeners (A and B). Some minor compounds sharing similar spectra of known chejuenolides were also mentioned in the original report, although their detailed structures were not disclosed because of their extremely limited quantities.…”

Talaromyces sp. Ethyl Acetate Crude Extract as Potential Mosquitocide to Control Culex pipiens quinquefasciatus

“…Besides Penicillium , vermistatin has been found in other taxa such as Talaromyces thailandensis [ 22 ], Guignardia sp. [ 23 ], Eurotium rubrum [ 24 ], and co-culture of Alternaria alternate and Streptomyces exfoliates [ 25 ] and co-culture of Penicillium sp. and Streptomyces fradiae [ 26 ].…”

“…Vermistatin is often extracted together with derivatives. Dihydrovermistatin, one of its derivatives, is often extracted together with vermistatin from Alternaria alternate [ 25 ], Penicillium rubrum [ 28 ], and Phoma sp. [ 29 ].…”

β-Lactams from the Ocean

“…Marine bacteria have significant potential as producing organisms of the tripyrrole prodiginines [ 71 ]. The prodiginines (represented by prodigiosin) demonstrate a breadth of biological activities, also including pronounced synergy with polymyxins against pathogenic Gram-negative bacteria [ 72 , 73 , 74 , 75 ].…”