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Unveiling an indole alkaloid diketopiperazine biosynthetic pathway that features a unique stereoisomerase and multifunctional methyltransferase
Diketopiperazine (DKP) natural products have diverse structures and biological functions. Here, the authors elucidate the biosynthetic pathway for indole alkaloid DKP nocardioazine B which includes DKP stereoisomerization by an unusual aspartate/glutamate racemase homolog and N- and C-methylation by a dual function methyltransferase.
- Garrett Deletti
- , Sajan D. Green
- & Amy L. Lane
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Article
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Emergence of a proton exchange-based isomerization and lactonization mechanism in the plant coumarin synthase COSY
Plant biosynthetic enzymes rapidly evolve to catalyze specialized reactions. Here, the authors present the crystal structure and mechanism of COSY, the enzyme involved in coumarin biosynthesis of the BAHD-acyltransferase family that catalyzes an intramolecular acyl transfer reaction through a proton exchange mechanism.
- Colin Y. Kim
- , Andrew J. Mitchell
- & Jing-Ke Weng
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Ligand-specific conformational change drives interdomain allostery in Pin1
Born et al. describe interdomain allostery in the two domain peptidyl-prolyl isomerase Pin1 upon binding of two ligands. These ligands couple population shifts of extended and compact states to changes in the catalytic site of Pin1.
- Alexandra Born
- , Janne Soetbeer
- & Beat Vögeli
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Article
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Galactose to tagatose isomerization at moderate temperatures with high conversion and productivity
Production of tagatose, a sugar substitute, by isomerization of galactose suffers from unfavorable enzymatic kinetics, low enzyme stability, and low equilibrium constant. Here, the authors simultaneously overcome these limitations by encapsulating l-arabinose isomerase in permeabilized Lactobacillus plantarum.
- Josef R. Bober
- & Nikhil U. Nair
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Article
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Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation
Novofumigatonin is a meroterpenoid found in the fungus Aspergillus novofumigatus. Here, the authors elucidate the biosynthetic pathway of novofumigatonin and show that the endoperoxidase NvfI and the endoperoxide isomerase NvfE are involved in it.
- Yudai Matsuda
- , Tongxuan Bai
- & Thomas O. Larsen
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Article
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Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin
Type IIA topoisomerases (topo2As) create transient double-strand DNA breaks. Here, the authors report structures showing how QPT-1 binds in the DNA/topo2A complex at the same site as the fluoroquinolone moxifloxacin, and discuss the potential for developing new classes of antibiotics.
- Pan F. Chan
- , Velupillai Srikannathasan
- & Michael N. Gwynn
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Article
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Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria
Fluoroquinolone antibiotics are widely used to treat serious bacterial infections, but resistance is an increasing problem. Here the authors describe the synthesis and characterization of novel deoxynybomycin derivatives that exhibit activity against fluoroquinolone-resistant infections in an in vivomodel.
- Elizabeth I. Parkinson
- , Joseph S. Bair
- & Paul J. Hergenrother
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Article
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Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation
Topoisomerases facilitate the progress of elongating polymerases during transcription. Zomerdijk and colleagues now demonstrate an additional role for this enzyme; their data suggest that Top2 can cleave DNA inducing topological changes at the ribosomal DNA promoter, which assists de novoassembly of the RNA polymerase I pre-initiation complex.
- Swagat Ray
- , Tatiana Panova
- & Joost C. B. M. Zomerdijk
A universal metabolite repair enzyme removes a strong inhibitor of the TCA cycle