ArticleBMC microbiology2014
Identification and characterization of the biosynthetic gene cluster of polyoxypeptin A, a potent apoptosis inducer.
Article in BMC microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 55 citations in OpenAlex.
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- Potentiality of Actinomycetia Prevalent in Selected Forest Ecosystems in Assam, India to Combat Multi-Drug-Resistant Microbial Pathogens.Metabolites · 2023Article
- Lunaemycins, New Cyclic Hexapeptide Antibiotics from the Cave Moonmilk-DwellerInternational journal of molecular sciences · 2023Article
- Recent advances on cyclodepsipeptides: biologically active compounds for drug research.Frontiers in microbiology · 2023Review
- Nocardia noduli sp. nov., a novel actinobacterium with biotechnological potential.Archives of microbiology · 2022Article
- Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines FromFrontiers in microbiology · 2022Article
- Enzymatic CJournal of the American Chemical Society · 2021Article
- A Machine Learning Bioinformatics Method to Predict Biological Activity from Biosynthetic Gene Clusters.Journal of chemical information and modeling · 2021Article
- Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores.Journal of the American Chemical Society · 2021Article
- Biosynthesis of depsipeptides, or Depsi: The peptides with varied generations.Protein science : a publication of the Protein Society · 2020Review
- Efficient Chemoenzymatic Synthesis of (2Tetrahedron · 2019Article
- Structural basis of the nonribosomal codes for nonproteinogenic amino acid selective adenylation enzymes in the biosynthesis of natural products.Journal of industrial microbiology & biotechnology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPolyoxypeptin A was isolated from a culture broth of Streptomyces sp. MK498-98 F14, which has a potent apoptosis-inducing activity towards human pancreatic carcinoma AsPC-1 cells. Structurally, polyoxypeptin A is composed of a C₁₅ acyl side chain and a nineteen-membered cyclodepsipeptide core that consists of six unusual nonproteinogenic amino acid residues (N-hydroxyvaline, 3-hydroxy-3-methylproline, 5-hydroxypiperazic acid, N-hydroxyalanine, piperazic acid, and 3-hydroxyleucine) at high oxidation states.
resultsA gene cluster containing 37 open reading frames (ORFs) has been sequenced and analyzed for the biosynthesis of polyoxypeptin A. We constructed 12 specific gene inactivation mutants, most of which abolished the production of polyoxypeptin A and only ΔplyM mutant accumulated a dehydroxylated analogue polyoxypeptin B. Based on bioinformatics analysis and genetic data, we proposed the biosynthetic pathway of polyoxypeptin A and biosynthetic models of six unusual amino acid building blocks and a PKS extender unit.
conclusionsThe identified gene cluster and proposed pathway for the biosynthesis of polyoxypeptin A will pave a way to understand the biosynthetic mechanism of the azinothricin family natural products and provide opportunities to apply combinatorial biosynthesis strategy to create more useful compounds.
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