ArticleJournal of natural products2012
Expression of the platencin biosynthetic gene cluster in heterologous hosts yielding new platencin congeners.
Article in Journal of natural products, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Divergent multifunctional P450s-empowered biosynthesis of bioactive tripterifordin and cryptic atiserenoids in Aconitum implies convergent evolution.Nature communications · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Transcriptional regulators of secondary metabolite biosynthesis in Streptomyces.World journal of microbiology & biotechnology · 2024Review
- Development of platensimycin, platencin, and platensilin overproducers by biosynthetic pathway engineering and fermentation medium optimization.Journal of industrial microbiology & biotechnology · 2024Article
- Bacterial terpenome.Natural product reports · 2021Review
- Semisynthesis and Biological Evaluation of Platencin Thioether Derivatives: Dual FabF and FabH Inhibitors against MRSA.ACS medicinal chemistry letters · 2021Article
- Complete genome sequences of Streptomyces spp. isolated from disease-suppressive soils.BMC genomics · 2019Article
- Cryptic and Stereospecific Hydroxylation, Oxidation, and Reduction in Platensimycin and Platencin Biosynthesis.Journal of the American Chemical Society · 2019Article
- Natural product drug discovery in the genomic era: realities, conjectures, misconceptions, and opportunities.Journal of industrial microbiology & biotechnology · 2019Article
- Challenges and opportunities for natural product discovery, production, and engineering in native producers versus heterologous hosts.Journal of industrial microbiology & biotechnology · 2019Review
- Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme.Nature chemical biology · 2018Article
- Boosting Secondary Metabolite Production and Discovery through the Engineering of Novel Microbial Biosensors.BioMed research international · 2018Review
- Platensimycin and platencin: Inspirations for chemistry, biology, enzymology, and medicine.Biochemical pharmacology · 2017Review
- In vivo instability of platensimycin and platencin: Synthesis and biological evaluation of urea- and carbamate-platensimycin.Bioorganic & medicinal chemistry · 2017Article
- Biosynthetic Origin of the Ether Ring in Platensimycin.Journal of the American Chemical Society · 2016Article
- Antibacterial sulfur-containing platensimycin and platencin congeners from Streptomyces platensis SB12029.Bioorganic & medicinal chemistry · 2016Article
- Synthetic biology to access and expand nature's chemical diversity.Nature reviews. Microbiology · 2016Review
- A genetically amenable platensimycin- and platencin-overproducer as a platform for biosynthetic explorations: a showcase of PtmO4, a long-chain acyl-CoA dehydrogenase.Molecular bioSystems · 2015Article
- Mechanisms of self-resistance in the platensimycin- and platencin-producing Streptomyces platensis MA7327 and MA7339 strains.Chemistry & biology · 2014Article
- Heterologous expression of natural product biosynthetic gene clusters in Streptomyces coelicolor: from genome mining to manipulation of biosynthetic pathways.Journal of industrial microbiology & biotechnology · 2014Review
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Authors and funding
6 authors.
Funding
Abstract
Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of bacterial and mammalian fatty acid synthases and have emerged as promising drug leads for both antibacterial and antidiabetic therapies. We have previously cloned and sequenced the PTM-PTN dual biosynthetic gene cluster from Streptomyces platensis MA7327 and the PTN biosynthetic gene cluster from S. platensis MA7339, the latter of which is composed of 31 genes encoding PTN biosynthesis, regulation, and resistance. We have also demonstrated that PTM or PTN production can be significantly improved upon inactivation of the pathway-specific regulator ptmR1 or ptnR1 in S. platensis MA7327 or MA7339, respectively. We now report engineered production of PTN and congeners in a heterologous Streptomyces host. Expression constructs containing the ptn biosynthetic gene cluster were engineered from SuperCos 1 library clones and introduced into five model Streptomyces hosts, and PTN production was achieved in Streptomyces lividans K4-114. Inactivation of ptnR1 was crucial for expression of the ptn biosynthetic gene cluster, thereby PTN production, in S. lividans K4-114. Six PTN congeners, five of which were new, were also isolated from the recombinant strain S. lividans SB12606, revealing new insights into PTN biosynthesis. Production of PTN in a model Streptomyces host provides new opportunities to apply combinatorial biosynthetic strategies to the PTN biosynthetic machinery for structural diversity.
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