ArticleMicrobial cell factories2022
Regulation of heterologous subtilin production in Bacillus subtilis W168.
Article in Microbial cell factories, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 23 citations in OpenAlex.
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- Increased Expression Levels of Thermophilic Serine Protease TTHA0724 through Signal Peptide Screening inInternational journal of molecular sciences · 2023Article
- Antimicrobial peptides from Bacillus spp. and strategies to enhance their yield.Applied microbiology and biotechnology · 2023Review
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- Tandem expression of Ganoderma sinense sesquiterpene synthase and IDI promotes the production of gleenol in E. coli.Applied microbiology and biotechnology · 2022Article
- Antibiotic profiling of wild-type bacilli led to the discovery of new lanthipeptide subtilin-producing Bacillus spizizenii strains whose 16S rDNA sequences differ from the B. spizizenii typing strain.International microbiology : the official journal of the Spanish Society for Microbiology · 2022Article
- Characterization of subtilosin gene in wild type Bacillus spp. and possible physiological role.Scientific reports · 2022Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSubtilin is a peptide antibiotic (lantibiotic) natively produced by Bacillus subtilis ATCC6633. It is encoded in a gene cluster spaBTCSIFEGRK (spa-locus) consisting of four transcriptional units: spaS (subtilin pre-peptide), spaBTC (modification and export), spaIFEG (immunity) and spaRK (regulation). Despite the pioneer understanding on subtilin biosynthesis, a robust platform to facilitate subtilin research and improve subtilin production is still a poorly explored spot.
resultsIn this work, the intact spa-locus was successfully integrated into the chromosome of Bacillus subtilis W168, which is the by far best-characterized Gram-positive model organism with powerful genetics and many advantages in industrial use. Through systematic analysis of spa-promoter activities in B. subtilis W168 wild type and mutant strains, our work demonstrates that subtilin is basally expressed in B. subtilis W168, and the transition state regulator AbrB strongly represses subtilin biosynthesis in a growth phase-dependent manner. The deletion of AbrB remarkably enhanced subtilin gene expression, resulting in comparable yield of bioactive subtilin production as for B. subtilis ATCC6633. However, while in B. subtilis ATCC6633 AbrB regulates subtilin gene expression via SigH, which in turn activates spaRK, AbrB of B. subtilis W168 controls subtilin gene expression in SigH-independent manner, except for the regulation of spaBTC. Furthermore, the work shows that subtilin biosynthesis in B. subtilis W168 is regulated by the two-component regulatory system SpaRK and strictly relies on subtilin itself as inducer to fulfill the autoregulatory circuit. In addition, by incorporating the subtilin-producing system (spa-locus) and subtilin-reporting system (P
conclusionsWithin this study, the model organism B. subtilis W168 was successfully established as a novel platform for subtilin biosynthesis and the underlying regulatory mechanism was comprehensively characterized. This work will not only facilitate genetic (engineering) studies on subtilin, but also pave the way for its industrial production. More broadly, this work will shed new light on the heterologous production of other lantibiotics.
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