Here we report an efficient CRISPR-Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover new compounds with interesting bioactivities.
Two new (1 and 2) and three known (3–5) carbamidocyclophanes were isolated from a cultured freshwater cyanobacterium Nostoc sp. (UIC 10274) obtained from a sample collected at Des Plaines, Illinois. Their planar structures and stereoconfigurations were determined by extensive spectroscopic analysis including 1D/2D NMR experiments, HRESIMS as well as CD spectroscopy. Carbamidocyclophane F (1) showed potent anti-Mycobacterium tuberculosis activity in the microplate Alamar blue assay and low-oxygen-recovery assay with MIC values of 0.8 and 5.4 µM, respectively. Carbamidocyclophane F (1) also displayed antimicrobial activities against the gram positive bacteria Staphylococcus aureus and Enterococcus faecalis with MIC values of 0.1 and 0.2 µM, respectively. Carbamidocyclophane F (1) and Carbamidocyclophane G (2) both showed antiproliferative activity against MDA-MB-435 and HT-29 human cancer cell lines with IC50 values in the range from 0.5 to 0.7 µM.
Two new cyclic lipopeptides, trichormamides
A (1)
and B (2), were isolated from the cultured freshwater
cyanobacterium Trichormus sp. UIC 10339. The strain
was obtained from a sample collected in Raven Lake in Northern Wisconsin.
The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses
including HRESIMS and 1D and 2D NMR experiments. The absolute configurations
of the amino acid residues were assigned by the advanced Marfey’s
method after acid hydrolysis. Trichormamide A (1) is
a cyclic undecapeptide containing two d-amino acid residues
(d-Tyr and d-Leu) and one β-amino acid residue
(β-aminodecanoic acid). Trichormamide B (2) is
a cyclic dodecapeptide characterized by the presence of four nonstandard
α-amino acid residues (homoserine, N-methylisoleucine,
and two 3-hydroxyleucines) and one β-amino acid residue (β-aminodecanoic
acid). Trichormamide B (2) was cytotoxic against MDA-MB-435
and HT-29 cancer cell lines with IC50 values of 0.8 and
1.5 μM, respectively.
The aroma components in Meilanchun sesame flavor style baijiu were identified by aroma extract dilution analysis (AEDA), quantitative analysis, aroma active compound recombination, and omission/addition experiments.
Extract from the cultured freshwater cf. Oscillatoria sp. UIC 10045 showed antiproliferative activity against HT-29 cell line. Bioassay-guided fractionation led to the isolation of two new cyclic lipopeptides, named trichormamides C (1) and D (2). The planar structures were determined by combined analyses of HRESIMS, Q-TOF ESIMS/MS, and 1D and 2D NMR spectra. The absolute configurations of the amino acid residues were assigned by the advanced Marfey’s analysis after partial and complete acid hydrolysis. Trichormamides C (1) is a cyclic undecapeptide and D (2) is a cyclic dodecapeptide, both containing a lipophilic β-aminodecanoic acid residue. Trichormamide C (1) displayed antiproliferative activities against HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 1.7 and 1.0 µM, respectively, as well as anti-Mycobacterium tuberculosis activity with MIC value of 23.8 µg/mL (17.3 µM). Trichormamide D (2) was found to be less potent against both HT-29 and MDA-MB-435 cancer cell lines with IC50 values of 11.5 and 11.7 µM, respectively.
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