Functional Characterization of <i>ttnI</i> Completing the Tailoring Steps for Tautomycetin Biosynthesis in <i>Streptomyces griseochromogenes</i>

The tautomycetin (TTN) biosynthetic gene cluster has been recently cloned and sequenced from <i>Streptomyces griseochromogenes</i>, unveiling four genes, <i>ttnCDFI</i>, as candidates to encode the tailoring steps for TTN biosynthesis. It is reported that (i) TtnC plays no essential role in TTN biosynthesis, (ii) TtnI catalyzes C-5 oxidation, and (iii) combining the previous findings with TtnFD, the tailoring steps from TTN F-1 to TTN take place in the order of TtnF-catalyzed C-1″/C-2″ dehydration, TtnD-catalyzed C-3″ decarboxylation, and TtnI-catalyzed C-5 oxidation

Specificity of the Ester Bond Forming Condensation Enzyme SgcC5 in C-1027 Biosynthesis

The SgcC5 condensation enzyme catalyzes the attachment of SgcC2-tethered (<i>S</i>)-3-chloro-5-hydroxy-β-tyrosine (<b>2</b>) to the enediyne core in C-1027 (<b>1</b>) biosynthesis. It is reported that SgcC5 (i) exhibits high stereospecificity toward the (<i>S</i>)-enantiomers of SgcC2-tethered β-tyrosine and analogues as donors, (ii) prefers the (<i>R</i>)-enantiomers of 1-phenyl-1,2-ethanediol (<b>3</b>) and analogues, mimicking the enediyne core, as acceptors, and (iii) can recognize a variety of donor and acceptor substrates to catalyze their regio- and stereospecific ester bond formations

MOESM15 of Designed biosynthesis of 25-methyl and 25-ethyl ivermectin with enhanced insecticidal activity by domain swap of avermectin polyketide synthase

Additional file 15: Figure S13. HMBC spectrum of compound 2

Characterization of Proapoptotic Compounds from the Bark of <i>Garcinia oblongifolia</i>

Twenty compounds from <i>Garcinia oblongifolia</i> were screened for proapoptotic activity using FRET-based HeLa-C3 sensor cells. Among them, oblongifolins F and G (<b>1</b> and <b>2</b>), 1,3,5-trihydroxy-13,13-dimethyl-2<i>H</i>-pyran­[7,6-<i>b</i>]­xanthone (<b>3</b>), nigrolineaxanthone T (<b>4</b>), and garcicowin B (<b>5</b>) showed significant proapoptotic activity at a concentration of 10 μM. Bioassessments were then performed to evaluate the potential of these compounds for therapeutic application. All five compounds showed significant cytotoxicity and caspase-3-activating ability in cervical cancer HeLa cells, with compounds <b>1</b> and <b>2</b> having the highest potencies. All five compounds specifically induced caspase-dependent apoptosis, which could be prevented by the pan-caspase inhibitor zVAD-fmk. In particular, <b>3</b> induced apoptosis through mitotic arrest. Compounds <b>1</b>–<b>5</b> displayed similar IC₅₀ values (3.9–16.5 μM) against the three cancer cell lines HeLa, MDA-MB-435, and HepG2. In addition, compounds <b>1</b>, <b>2</b>, and <b>4</b> exhibited similar and potent IC₅₀ values (2.4–5.1 μM) against several breast and colon cancer cell lines, including those overexpressing either HER2 or P-glycoprotein. HER2 and P-glycoprotein are known factors that confer resistance to anticancer drugs in cancer cells. This is the first study on the cytotoxicity, caspase-3-activing ability, and specificity of proapoptotic compounds isolated from <i>G. oblongifolia</i> in HeLa cells. The potential application of these compounds against HER2- or P-glycoprotein-overexpressing cancer cells was investigated

Enediyne Polyketide Synthases Stereoselectively Reduce the β‑Ketoacyl Intermediates to β‑d‑Hydroxyacyl Intermediates in Enediyne Core Biosynthesis

PKSE biosynthesizes an enediyne core precursor from decarboxylative condensation of eight malonyl-CoAs. The KR domain of PKSE is responsible for iterative β-ketoreduction in each round of polyketide chain elongation. KRs from selected PKSEs were investigated in vitro with β-ketoacyl-SNACs as substrate mimics. Each of the KRs reduced the β-ketoacyl-SNACs stereoselectively, all affording the corresponding β-d-hydroxyacyl-SNACs, and the catalytic efficiencies (<i>k</i>_cat/<i>K</i>_M) of the KRs increased significantly as the chain length of the β-ketoacyl-SNAC substrate increases

A new actinomycin Z analogue with an additional oxygen bridge between chromophore and <i>β</i>-depsipentapeptide from <i>Streptomyces</i> sp. KIB-H714

<p>Actinomycin Z₆ (<b>1</b>), a new member of the actinomycin family, along with three congeners of the Z-type (Z₁, Z₃, Z₅) actinomycins, are produced from <i>Streptomyces</i> sp. KIB-H714. Their structures were authenticated by comprehensive spectroscopic data interpretation. Different from all the reported Z-type actinomycins, the <i>β</i>-ring of the new compound actinomycin Z₆ includes an additional ring linked between the actinoyl chromophore and <i>β</i>-peptidolactone. In Z₃ and Z₅, the L-threonine in <i>β</i>-depsipeptide is replaced by the unusual 4-chlorothreonine, an amino acid rarely found in actinomycin family. All isolates were evaluated for cytotoxicity against five human tumor cell lines and for inhibitory activity against <i>Candida albicans</i> and <i>Staphylococcus aureus</i>.</p

Tropolone Ring Construction in the Biosynthesis of Rubrolone B, a Cationic Tropolone Alkaloid from Endophytic <i>Streptomyces</i>

Rubrolones are tropolonoid natural products with a unique carbon skeleton. Extensive secondary metabolite analysis of the endophytic <i>Streptomyces</i> sp. KIB-H033 revealed a new class of rubrolone analogue possessing a rare benzoic acid–pyridine inner salt moiety. Precursor feeding with [¹³C]-acetate revealed a labeling pattern consistent with tropolone moiety construction via type-II PKS chemistry followed by complex oxidative rearrangements. This bacterial biosynthetic route represents a surprising departure from fungal tropolone assembly during stipitatic acid biosynthesis

Neaumycin: A New Macrolide from <i>Streptomyces</i> sp. NEAU-x211

Neaumycin, a new 30-membered macrolide featuring an internal diester bridge, a molecular architecture that is unprecedented among known macrolide natural products, was isolated from a soil actinomycete strain <i>Streptomyces</i> sp. NEAU-x211. The structure of neaumycin was elucidated on the basis of comprehensive mass and NMR spectroscopic interpretation, including the relative stereochemistry of four independent coupling systems

A new myrsinol-type diterpene polyester from <i>Euphorbia dracunculoides</i> Lam

<div><p>A new myrsinol-type diterpene polyester, 14-deoxo-3β-<i>O</i>-propinoyl-2α,5α,7β,15β-tetra-<i>O</i>-acetyl-14α-<i>O</i>-benzoyl-myrsinol (<b>1</b>), and its known analogue, 14-deoxo-3β-<i>O</i>-prorionyl-5α,15β-di-<i>O</i>-acetyl-7β-<i>O</i>-nicotinoyl-myrsinol-14β-acetate (<b>2</b>), together with a monoterpenoid, pubinernoid A (<b>3</b>), two indole alkaloids, neoechinulin A (<b>4</b>) and dihydroxyisoechinulin A (<b>5</b>), two benzene derivatives, siringin (<b>6</b>) and (3-methoxyphenyl) acetic acid (<b>7</b>), were isolated from the 70% acetone extract of the aerial parts of <i>Euphorbia dracunculoides</i> Lam. Their structures were elucidated on the basis of spectroscopic evidence and comparison with literature reports. The absolute configuration of <b>1</b> was deduced by comparing experimental and calculated ECD spectra. Among them, compounds <b>4</b> and <b>5</b> were first obtained from the plant source. In addition, the ¹³C NMR data of compound <b>2</b> was reported for the first time.</p></div

New Duclauxamide from <i>Penicillium manginii</i> YIM PH30375 and Structure Revision of the Duclauxin Family

Duclauxamide A1 (<b>1</b>), a new polyketide-derived heptacyclic oligophenalenone dimer with a <i>N</i>-2-hydroxyethyl moiety, was isolated from <i>Penicillium manginii</i> YIM PH30375. Spectroscopic analysis, X-ray single crystal diffraction, and ¹³C NMR DFT calculations confirmed that compound <b>1</b> and other duclauxin analogues possess the unified <i>S</i> configuration at C-9′, which corrects a long-standing misrepresentation of duclauxins as C-9′<i>R</i> epimers. A plausible biosynthetic pathway for duclauxins is proposed on the basis of previous acetate labeling results for duclauxin and sclerodin