ArticleMicrobial cell factories2019
Exploring novel herbicidin analogues by transcriptional regulator overexpression and MS/MS molecular networking.
Article in Microbial cell factories, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 14 citations in OpenAlex.
- Roles of LuxR-family regulators in the biosynthesis of secondary metabolites in Actinobacteria.World journal of microbiology & biotechnology · 2022Review
- Halogenase-Targeted Genome Mining Leads to the Discovery of (±) Pestalachlorides A1a, A2a, and Their Atropisomers.Antibiotics (Basel, Switzerland) · 2022Article
- Integrated Metabolomic-Genomic Workflows Accelerate Microbial Natural Product Discovery.Analytical chemistry · 2022Review
- Identification of the Early Steps in Herbicidin Biosynthesis Reveals an Atypical Mechanism ofJournal of the American Chemical Society · 2022Article
- Complete Genome Sequence of Streptomyces albus Strain G153.Microbiology resource announcements · 2022Article
- UPLC-Q-TOF-MS/MS Analysis ofFrontiers in microbiology · 2022Article
- Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators inFrontiers in microbiology · 2022Article
- New Polyketides from the Antarctic FungusMarine drugs · 2021Article
- Production of novel pladienolide analogues through native expression of a pathway-specific activator.Chemical science · 2020Article
- Coordinated regulation for nature products discovery and overproduction inSynthetic and systems biotechnology · 2020Article
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9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHerbicidin F has an undecose tricyclic furano-pyrano-pyran structure with post-decorations. It was detected from Streptomyces mobaraensis US-43 fermentation broth as a trace component by HPLC-MS analysis. As herbicidins exhibit herbicidal, antibacterial, antifungal and antiparasitic activities, we are attracted to explore more analogues for further development.
resultsThe genome of S. mobaraensis US-43 was sequenced and a herbicidin biosynthetic gene cluster (hcd) was localized. The cluster contains structural genes, one transporter and three potential transcription regulatory genes. Overexpression of the three regulators respectively showed that only hcdR2 overexpression significantly improved the production of herbicidin F, and obviously increased the transcripts of 7 structural genes as well as the transporter gene. After performing homology searches using BLASTP in the GenBank database, 14 hcd-like clusters were found with a cluster-situated hcdR2 homologue. These HcdR2 orthologues showed overall structural similarity, especially in the C-terminal DNA binding domain. Based on bioinformatics analysis, a 21-bp consensus binding motif of HcdR2 was detected within 30 promoter regions in these genome-mined clusters. EMSA results verified that HcdR2 bound to the predicted consensus sequence. Additionally, we employed molecular networking to explore novel herbicidin analogues in hcdR2 overexpression strain. As a result, ten herbicidin analogues including six new compounds were identified based on MS/MS fragments. Herbicidin O was further purified and confirmed by
conclusionsA herbicidin biosynthetic gene cluster (hcd) was identified in S. mobaraensis US-43. HcdR2, a member of LuxR family, was identified as the pathway-specific positive regulator, and the production of herbicidin F was dramatically increased by overexpression of hcdR2. Combined with molecular networking, ten herbicidin congeners including six novel herbicidin analogues were picked out from the secondary metabolites of hcdR2 overexpression strain. The orthologues of herbicidin F pathway-specific regulator HcdR2 were present in most of the genome-mined homologous biosynthetic gene clusters, which possessed at least one consensus binding motif with LuxR family characteristic. These results indicated that the combination of overexpression of hcdR2 orthologous regulator and molecular networking might be an effective way to exploit the "cryptic" herbicidin-related biosynthetic gene clusters for discovery of novel herbicidin analogues.
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