Genomic and chemical decryption of the Bacteroidetes phylum for its potential to biosynthesize natural products

Abstract

With progress in genome sequencing and data sharing, 1000s of bacterial genomes are publicly available. Genome mining – using bioinformatics tools in terms of biosynthetic gene cluster (BGC) identification, analysis and rating – has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing the genetic potential of the phylum Bacteroidetes revealed Chitinophaga as the most talented genus in terms of BGC abundance and diversity. Guided by the computational predictions, we conducted a metabolomics and bioactivity driven NP discovery program on 25 Chitinophaga strains. High numbers of peerless strain-specific metabolite buckets confirmed the upfront predicted biosynthetic potential and revealed a tremendous uncharted chemical space. Sourcing this dataset, we isolated the new iron chelating nonribosomally synthesized cyclic tetradeca- and pentadecalipodepsipeptide antibiotics chitinopeptins with activity against Candida, produced by C. eiseniae DSM 22224 and C. flava KCTC 62435, respectively.

Novel Glycerophospholipid, Lipo- and N-acyl Amino Acids from Bacteroidetes: Isolation, Structure Elucidation and Bioactivity

“…This novel tripeptide LAA family is most closely related to the intensively studied glycine-serine dipeptide lipids 654 and 430 (2). Interestingly, with lipid 430 (2), only the de-esterified hydrolysis product of lipid 654 [34] was detected in the methanolic extracts of 23 of 25 Chitinophaga strains generated in our previous study [46]. Recent intensive studies of human pathogenic Bacteroidetes such as P. gingivalis revealed both dipeptide lipids to engage TLR2 [34].…”

“…In the current study, we described the characterization and structure elucidation of the unknown previously determined core lipids of the Bacteroidetes genus Chitinophaga [46]. Interestingly, we observed the highest production titers of three of the four lipids in extracts of Olivibacter sp.…”

“…In agreement with the chemical shift of the HSQC-correlating carbon atoms C-2 and C-4 (δ C-2 70.9 ppm, δ C-4 69.5 ppm), hydroxylation was determined at both sites, thereby identifying 4 as (2,3,4-trihydroxy-15-methylhexadecanoyl)glycine (Figure 2; Table S2). In contrast with its de-esterified hydrolysis product lipid 430 (2) [36], lipid 654 (m/z 655.525 [M + H] + ) carrying an additional ester-linked iso-pentadecenoic acid (iso-C 15:0 ) was not observed in our previously generated Chitinophaga extracts (Table S1) [46]. Nevertheless, we searched for corresponding lipid 654 analogs because LAA 1 represents a close derivative of lipid 430 (2) containing an additional ornithine amino acid attached to the glycine-serine dipeptide.…”

“…3908 S1). Based on their MS/MS fragmentation pattern, similar lipid moieties were postulated, suggesting a structural relationship [46].…”

“…In a previous study, we identified the 'core' metabolome of the Bacteroidetes genus Chitinophaga, consisting of only seven metabolites [46]. We postulated a structural relationship among four of them based on their MS/MS fragmentation pattern, which suggested them to be unknown LAAs and LPEs.…”