Iterative Methylation Leads to 3-Methylchuangxinmycin Production in CPCC 200056.

A new congener of chuangxinmycin (CM) was identified from CPCC 200056. Its structure was determined as 3-methylchuangxinmycin (MCM) by 1D and 2D NMR. MCM could be generated from CM by heterologous expression of the vitamin B-dependent radical SAM enzyme CxnA/A responsible for methylation of 3-demethylchuangxinmycin (DCM) in CM biosynthesis, indicating that CxnA/A could perform iterative methylation for MCM production.

Mining and characterization of the PKS-NRPS hybrid for epicoccamide A: a mannosylated tetramate derivative from Epicoccum sp. CPCC 400996.

Background: Genomic analysis indicated that the genomes of ascomycetes might carry dozens of biosynthetic gene clusters (BGCs), yet many clusters have remained enigmatic. The ascomycete genus Epicoccum, belonging to the family Didymellaceae, is ubiquitous that colonizes different types of substrates and is associated with phyllosphere or decaying vegetation. Species of this genus are prolific producers of bioactive substances.

Isatropolone/isarubrolone C from Streptomyces with biological activity of inducing incomplete autophagy.

Isatropolones/isarubrolones are Streptomyces secondary metabolites featuring a tropolone ring in the pentacyclic scaffolds of these molecules. They are able to induce complete autophagy in human HepG2 cells. Here, methyl isatropolones (1-2) and isarubrolone (3) are identified from Streptomyces CPCC 204095.

Dihydroisatropolone C from and Its Implication in Tropolone-Ring Construction for Isatropolone Biosynthesis.

Isatropolones/isarubrolones are actinomycete secondary metabolites featuring a tropolone-ring in their structures. From the isatropolone/isarubrolone producer sp. CPCC 204095, 7,12-dihydroisatropolone C (HITC) is discovered and identified as a mixture of two interchangeable diastereomers differing in the C-6 configuration.

Mintaimycins, a Group of Novel Peptide Metabolites from sp. C-3509.

A group of peptide metabolites (-), designated as mintaimycins, were isolated from sp. C-3509. The planar structures of mintaimycins were determined by combination of mass spectrometry, 1D and 2D NMR spectroscopy, and the stereochemistry of mintaimycins were partially resolved by Marfey's or Mosher's method.

Cytochrome P450 Monooxygenase for Catalyzing C-42 Hydroxylation of the Glycine-Derived Fragment in Hangtaimycin Biosynthesis.

A hybrid -AT PKS/NRPS gene cluster was identified with defined boundaries for hangtaimycin biosynthesis in CPCC200148. Deoxyhangtaimycin, a new derivative of hangtaimycin, was identified from the gene knockout mutant. In vitro biochemical assays demonstrated that the cytochrome P450 monooxygenase Htm11 was responsible for the stereoselective hydroxylation of deoxyhangtaimycin to hangtaimycin.

The Cytochrome P450 Catalyzing C-S Bond Formation in S-Heterocyclization of Chuangxinmycin Biosynthesis.

Microbial sulfur-containing secondary metabolites show various biological activities, but the C-S bond-forming in their biosynthetic metabolism has not been thoroughly understood. Here, we present genetic, biochemical and structural characterization of a cytochrome P450 monooxygenase CxnD exhibiting C-S bond forming activity in S-heterocyclization of chuangxinmycin biosynthesis. In vivo and in vitro analyses demonstrated that CxnD generated an indole-fused dihydrothiopyran skeleton from a L-Trp-derived thiol intermediate.

Cervinomycins C with cytotoxic and antibacterial activity from Streptomyces sp. CPCC 204980.

Polycyclic xanthones are secondary metabolites from actinomycetes and cervinomycin A and B are bioactive 26-membered polycyclic xanthones from Streptomyces sp. CPCC 204980. Herein, we report cervinomycins C (1-4) from the same strain.

1-hydroxy-7-oxolavanducyanin and Δ-6″-hydroxynaphthomevalin from Streptomyces sp. CPCC 203577.

Lavanducyanin is a bioactive phenazine-containing secondary metabolite, and naphthomevalin is an antibacterial polyketide secondary metabolite. Herein, new analogues of lavanducyanin (2) and of naphthomevalin (4), together with lavanducyanin (1) and naphthomevalin (3), were identified from Streptomyces sp. CPCC 203577, an actinomycete soil isolate.

Cytotoxic and Antibacterial Cervinomycins B from a Species.

AntiSMASH analysis of genome DNA of CPCC 204980, a soil isolate with potent antibacterial activity, revealed a gene cluster for polycyclic xanthones. A subsequent chemical study confirmed that the microorganism produced polycyclic xanthone cervinomycin A () and the new congeners cervinomycins B (-). The structures of - were determined by comprehensive analyses of MS and NMR data, which indicated that - featured a common dihydro-D ring in the polycyclic xanthone core moiety of their molecules.

Genome-Guided Discovery of Pretilactam from ATCC 31565.

is a small but well-known genus of actinomycetes for production of ansamitocin, the payload component of antibody-drug conjugates against cancers. However, the secondary metabolite production profile of ATCC 31565, the most famous producer of ansamitocin, has never been fully explored. Our antiSMASH analysis of the genomic DNA of ATCC 31565 revealed a NRPS-PKS gene cluster for polyene macrolactam.

Isarubrolones Containing a Pyridooxazinium Unit from Streptomyces as Autophagy Activators.

Isarubrolones are bioactive polycyclic tropoloalkaloids from Streptomyces. Three new isarubrolones (2-4), together with the known isarubrolone C (1) and isatropolones A (5) and C (6, 3( R)-hydroxyisatropolone A), were identified from Streptomyces sp. CPCC 204095.

Geninthiocins C and D from Streptomyces as 35-membered macrocyclic thiopeptides with modified tail moiety.

Geninthiocin is a thiopeptide with 35-membered macrocyclic core moiety. It has potent anti-Gram-positive (G) bacteria activity. Herein, we reported two new congeners (2-3) of geninthiocin (geninthiocin A, 1) from Streptomyces sp.

Quinohemanine, a quinoxalinone-bohemamine hybrid compound from Streptomyces sp. CPCC 200497.

A quinoxalinone-bohemamine hybrid compound quinohemanine (1), together with 1-methyl-2(H)-quinoxalin-2-one (2), was isolated from Streptomyces sp. CPCC 200497, a producer of quinomycins and bohemamines. Compounds 1 and 2 were purified using standard chromatographic methods, and their structures were defined through interpretation of HRMS, 1D, and 2D NMR data.

Cytotoxic Dibohemamines D-F from a Streptomyces Species.

Three dimeric analogues of bohemamines, dibohemamines D-F (1-3), together with dibohemamine A (4), were isolated from Streptomyces sp. CPCC 200497. Their structures were solved using a combination of mass spectrometry, 1D and 2D NMR spectroscopy, and CD.

Three structurally-related impurities in norvancomycin drug substance.

Norvancomycin (NVCM) is widely used in China to treat bacterial infections of Gram-positive cocci and bacilli, especially infections of methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis. This study is a chemical investigation of the drug substance of NVCM, and led to the identification, by 1D, 2D NMR spectra and HRESIMS, of three as yet undescribed impurities, one D-O-E ring expanded NVCM analog (1) and two derivatives of NVCM lacking sugars (2, 3).

Binding of a biosynthetic intermediate to AtrA modulates the production of lidamycin by Streptomyces globisporus.

The control of secondary production in streptomycetes involves the funneling of environmental and physiological signals to the cluster-situated (transcriptional) regulators (CSRs) of the biosynthetic genes. For some systems, the binding of biosynthetic products to the CSR has been shown to provide negative feedback. Here we show for the production of lidamycin (C-1027), a clinically relevant antitumor agent, by Streptomyces globisporus that negative feedback can extend to a point higher in the regulatory cascade.

Aromatic acid derivatives from the lateral roots of Aconitum carmichaelii.

Seven new aromatic acid derivatives (1-7), together with five known analogs, were isolated from the lateral roots of Aconitum carmichaelii. Structures of the new compounds were determined by spectroscopic and chemical methods as 4-methyl ( - )-(R)-hydroxyeucomate (1), 4-butyl ( - )-(R)-hydroxyeucomate (2), 4-butyl-1-methyl (+)-(R)-2-O-(4'-hydroxy-3'-methoxybenzoyl)malate (3), 1-butyl-4-methyl (+)-(R)-2-O-(4'-hydroxy-3'-methoxybenzoyl)malate (4), dimethyl (+)-(R)-2-O-(4'-hydroxy-3'-methoxybenzoyl)malate (5), dimethyl (+)-(R)-2-O-(4'-hydroxybenzoyl)malate (6), and methyl ( ± )-3-(4'-hydroxy-3'-methoxyphenyl)-3-sulfopropionate (7), respectively. Compounds 1 and 2 are 2-benzylmalates (eucomate derivatives), 3-6 belong to 2-O-benzoylmalates, and 7 is a rare phenylpropionate containing a sulfonic acid group.

19-[(1'S,4'R)-4'-Hydroxy-1'-methoxy-2'-oxopentyl]geldanamycin, a natural geldanamycin analogue from Streptomyces hygroscopicus 17997.

A novel natural geldanamycin analogue was discovered in Streptomyces hygroscopicus 17997. Its 4,5-dihydro form was also identified in the gdmP gene disruption mutant of Streptomyces hygroscopicus 17997. The structures of the two compounds were determined to be 19-[(1'S,4'R)-4'-hydroxy-1'-methoxy-2'-oxopentyl]geldanamycin (1) and 19-[(1'S,4'R)-4'-hydroxy-1'-methoxy-2'-oxopentyl]-4,5-dihydrogeldanamycin (2), respectively, by extensive spectroscopic data analysis, including 2D NMR, modified Mosher's method, and electronic circular dichroism.