ArticleScientific reports2016
Genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via Red/ET recombineering.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- The Disorazole Z Family of Highly Potent Anticancer Natural Products from Sorangium cellulosum: Structure, Bioactivity, Biosynthesis, and Heterologous Expression.Microbiology spectrum · 2023Article
- Genetic manipulation and tools in myxobacteria for the exploitation of secondary metabolism.Engineering microbiology · 2023Review
- Engineering ofFrontiers in microbiology · 2022Article
- Biotechnological production optimization of argyrins - a potent immunomodulatory natural product class.Microbial biotechnology · 2022Article
- Stepwise genetic engineering of Pseudomonas putida enables robust heterologous production of prodigiosin and glidobactin A.Metabolic engineering · 2021Article
- A Natural Product Chemist's Guide to Unlocking Silent Biosynthetic Gene Clusters.Annual review of biochemistry · 2021Review
- Natural products in drug discovery: advances and opportunities.Nature reviews. Drug discovery · 2021Review
- Discovery, Bioactivity Evaluation, Biosynthetic Gene Cluster Identification, and Heterologous Expression of Novel Albofungin Derivatives.Frontiers in microbiology · 2021Article
- Recent Advances in Strategies for the Cloning of Natural Product Biosynthetic Gene Clusters.Frontiers in bioengineering and biotechnology · 2021Review
- The Genome of the Plant-Associated Lactic Acid Bacterium Lactococcus lactis KF147 Harbors a Hybrid NRPS-PKS System Conserved in Strains of the Dental Cariogenic Streptococcus mutans.Current microbiology · 2020Article
- Evolution and Diversity of Assembly-Line Polyketide Synthases.Chemical reviews · 2019Review
- Genetic platforms for heterologous expression of microbial natural products.Natural product reports · 2019Review
- Whole transcriptome analysis and gene deletion to understand the chloramphenicol resistance mechanism and develop a screening method for homologous recombination in Myxococcus xanthus.Microbial cell factories · 2019Article
- Genome Editing in Model StrainBiomolecules · 2018Article
- Breaking the silence: new strategies for discovering novel natural products.Current opinion in biotechnology · 2017Review
- Increasing on-target cleavage efficiency for CRISPR/Cas9-induced large fragment deletion in Myxococcus xanthus.Microbial cell factories · 2017Article
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Authors and funding
7 authors.
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Abstract
Disorazol, a macrocyclic polykitide produced by the myxobacterium Sorangium cellulosum So ce12 and it is reported to have potential cytotoxic activity towards several cancer cell lines, including multi-drug resistant cells. The disorazol biosynthetic gene cluster (dis) from Sorangium cellulosum (So ce12) was identified by transposon mutagenesis and cloned in a bacterial artificial chromosome (BAC) library. The 58-kb dis core gene cluster was reconstituted from BACs via Red/ET recombineering and expressed in Myxococcus xanthus DK1622. For the first time ever, a myxobacterial trans-AT polyketide synthase has been expressed heterologously in this study. Expression in M. xanthus allowed us to optimize the yield of several biosynthetic products using promoter engineering. The insertion of an artificial synthetic promoter upstream of the disD gene encoding a discrete acyl transferase (AT), together with an oxidoreductase (Or), resulted in 7-fold increase in disorazol production. The successful reconstitution and expression of the genetic sequences encoding for these promising cytotoxic compounds will allow combinatorial biosynthesis to generate novel disorazol derivatives for further bioactivity evaluation.
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