ArticleACS chemical biology2016
Engineering of New Pneumocandin Side-Chain Analogues from Glarea lozoyensis by Mutasynthesis and Evaluation of Their Antifungal Activity.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Mitochondrial cardiolipin sequestration of caspofungin underliesbioRxiv : the preprint server for biology · 2026Article
- Biosynthesis of the Fungal Cyclic Lipodepsipeptide Pleosporacin, a New Selective Inhibitor of the Phytopathogen Botrytis cinerea.Chembiochem : a European journal of chemical biology · 2025Article
- Metabolic engineering ofSynthetic and systems biotechnology · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Branching and converging pathways in fungal natural product biosynthesis.Fungal biology and biotechnology · 2022Review
- FunOrder: A robust and semi-automated method for the identification of essential biosynthetic genes through computational molecular co-evolution.PLoS computational biology · 2021Article
- Engineering and elucidation of the lipoinitiation process in nonribosomal peptide biosynthesis.Nature communications · 2021Article
- Echinocandins: structural diversity, biosynthesis, and development of antimycotics.Applied microbiology and biotechnology · 2021Review
- Acrophiarin (antibiotic S31794/F-1) from Penicillium arenicola shares biosynthetic features with both Aspergillus- and Leotiomycete-type echinocandins.Environmental microbiology · 2020Article
- Effect of SDS on release of intracellular pneumocandin BApplied microbiology and biotechnology · 2019Article
- Metabolomics profiling reveals the mechanism of increased pneumocandin BJournal of industrial microbiology & biotechnology · 2018Article
- Cryptic Production ofApplied and environmental microbiology · 2018Article
- Effects of Cotton Seed Powder as the Seed Medium Nitrogen Source on the Morphology and Pneumocandin BFrontiers in microbiology · 2018Article
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Authors and funding
10 authors.
Funding
Abstract
Pneumocandins are lipohexapeptides of the echinocandin family that inhibit fungal 1,3-β-glucan synthase. Most of the pathway steps have been identified previously. However, the lipoinitiation reaction has not yet been experimentally verified. Herein, we investigate the lipoinitiation step of pneumocandin biosynthesis in Glarea lozoyensis and demonstrate that the gene product, GLligase, catalyzes this step. Disruption of GLHYD, a gene encoding a putative type II thioesterase and sitting upstream of the pneumocandin acyl side chain synthase gene, GLPKS4, revealed that GLHYD was necessary for optimal function of GLPKS4 and to attain normal levels of pneumocandin production. Double disruption of GLHYD and GLPKS4 did not affect residual function of the GLligase or GLNRPS4. Mutasynthesis experiments with a gene disruption mutant of GLPKS4 afforded us an opportunity to test the substrate specificity of GLligase in the absence of its native polyketide side chain to diversify pneumocandins with substituted side chains. Feeding alternative side chain precursors yielded acrophiarin and four new pneumocandin congeners with straight C14, C15, and C16 side chains. A comprehensive biological evaluation showed that one compound, pneumocandin I (5), has elevated antifungal activity and similar hemolytic activity compared to pneumocandin B
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