ABSTRACT
A new hexaketide acid esterified by the 17-hydroxyl group of 16,17-dihydroxycyclooctatin, namely 17-[16,17-dihydroxycyclooctatinyl]-hexaketide ester (1), a member of the group of rare bacterial diterpenes with a fused 5-8-5 ring system was isolated from strain Streptomyces sp. SR107. The structure was determined on the basis of its spectral data (1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, IR and HR-ESI-MS). The antibacterial activity was also evaluated in this paper.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Streptomyces/chemistry , Bacteria/drug effects , Diterpenes/metabolism , Esters/chemistry , Esters/pharmacology , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Divergolides are a group of structurally unprecedented ansamacrolactam antibiotics with antibacterial and antitumor activities. A biosynthetic gene cluster predicted to encode the biosynthesis of divergolides was cloned and sequenced from endophytic Streptomyces sp. W112. The gene cluster of divergolides (div) spans a DNA region of 61-kb and consists of 20 open reading frames (ORFs) that encode polyketide synthases (PKSs), enzymes for the synthesis of AHBA and PKS extender units, and post-PKS modifications, proposed regulators, and putative transporters. Disruption of the AHBA synthase gene (divK) completely abolished the production of divergolides proved its involvement in the biosynthesis of divergolides. Bioinformatics analysis suggested that the regulatory gene div8 in div gene cluster might encode a positive regulator for the biosynthesis of divergolides. Constitutive overexpression of div8 improved the production of divergolides E, implying that div gene cluster maybe responsible for the biosynthesis of divergolides. These findings set the stage for fully investigating the biosynthesis of divergolides and rational engineering of new divergolide analogs by genetic modifications, and pave the way to further improve the production of divergolides.
Subject(s)
Bacterial Proteins/genetics , Macrolides/metabolism , Multigene Family , Streptomyces/genetics , Aminobenzoates/metabolism , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Biosynthetic Pathways/genetics , Cloning, Molecular , Gene Expression Regulation, Bacterial , Genomic Library , Hydro-Lyases/genetics , Hydro-Lyases/metabolism , Hydroxybenzoates/metabolism , Macrolides/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Open Reading Frames/genetics , Polyketide Synthases/genetics , Polyketide Synthases/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Spectrometry, Mass, Electrospray Ionization , Streptomyces/metabolismABSTRACT
Two pairs of geometrical isomers - cuevaenes A (1) and C (3) as well as cuevaenes D (4) and E (5) - and cuevaene B (2) were isolated from gdmAI-disrupted Streptomyces sp. LZ35. The constitution of cuevaene C (3) was found to be identical to cuevaene A (1) by means of NMR spectroscopy and high resolution mass spectrometry. However, the relative configurations of the triene side chain moieties were determined to be different. It was established on the basis of spectroscopic data that cuevaenes D (4) and E (5) are amides and geometrical isomers. Cuevaenes A-C (1-3) displayed moderate activity against Gram-positive bacteria (e.g., Bacillus subtilis strain ATCC 11060) and modest activity against fungi (e.g., Fusarium verticillioides strain S68 and Rhizoctonia solani strain GXE4). However, cuevaenes D (4) and E (5) showed no inhibitory activity against any of the tested microbes.
