Cyclic Heptapeptides, Cordyheptapeptides C–E, from the Marine-Derived Fungus <i>Acremonium persicinum</i> SCSIO 115 and Their Cytotoxic Activities

Three new cycloheptapeptides, cordyheptapeptides C–E (<b>1</b>–<b>3</b>), were isolated from the fermentation extract of the marine-derived fungus <i>Acremonium persicinum</i> SCSIO 115. Their planar structures were elucidated on the basis of extensive MS, as well as 1D and 2D (COSY, HMQC, and HMBC) NMR spectroscopic data analyses. The absolute configurations of the amino acid residues were determined by single-crystal X-ray diffraction, Marfey’s method, and chiral-phase HPLC analysis. Compounds <b>1</b> and <b>3</b> displayed cytotoxicity against SF-268, MCF-7, and NCI-H460 tumor cell lines with IC₅₀ values ranging from 2.5 to 12.1 μM

Identification of the Biosynthetic Gene Cluster for the Anti-infective Desotamides and Production of a New Analogue in a Heterologous Host

The desotamides (DSAs) are potent antibacterial cyclohexapeptides produced by <i>Streptomyces scopuliridis</i> SCSIO ZJ46. We have identified the 39-kb <i>dsa</i> biosynthetic gene cluster by whole-genome scanning. Composed of 17 open reading frames, the cluster codes for four nonribosomal peptide synthetases and associated resistance, transport, regulatory, and precursor biosynthesis proteins. Heterologous expression of the <i>dsa</i> gene cluster in <i>S. coelicolor</i> M1152 afforded desotamides A and B and the new desotamide G. Cluster identification and its demonstrated amenability to heterologous expression provide the foundation for future mechanistic studies as well as the generation of new and potentially clinically significant DSA analogues

MOESM1 of Characterization and heterologous expression of the neoabyssomicin/abyssomicin biosynthetic gene cluster from Streptomyces koyangensis SCSIO 5802

Additional file 1: Table S1. Bacteria used in this study. Table S2. Plasmids used in this study. Table S3. Primers used in this study. Figure S1. Chemical structures of tetronate-containing natural products and the unique set of five highly conserved genes responsible for tetronate biosynthesis. Figure S2. HPLC analyses of fermentation extracts of the inactivated mutants of boundary genes. Figure S3. Alignments of seven KS domains of AbmB1–B3. Figure S4. Alignments of five KR domains of AbmB1–B2. Figure S5. Alignments of five DH domains of AbmB1–B2. Figure S6. Alignments of five AT domains of AbmB1–B2. Figure S7. Alignments of AbmT with the typical type II TEs. Figure S8. The 14 transmembrane helices of AbmD. Figure S9. Alignments of AbmI with previously characterized SARP regulators. Figure S10. Alignments of AbmH with previously characterized LuxR-regulators. Figure S11. The quantitative HPLC standard curve for abyssomicin 2. Figures S12–S30. Disruption of 19 abm-related genes in wild-type S. koyangensis SCSIO 5802 via PCR-targeting

Biosynthesis of 9‑Methylstreptimidone Involves a New Decarboxylative Step for Polyketide Terminal Diene Formation

9-Methylstreptimidone is a glutarimide antibiotic showing antiviral, antifungal, and antitumor activities. Genome scanning, bioinformatics analysis, and gene inactivation experiments reveal a gene cluster responsible for the biosynthesis of 9-methylstreptimidone in <i>Streptomyces himastatinicus</i>. The unveiled machinery features both acyltransferase- and thioesterase-less iterative use of module 5 as well as a branching module for glutarimide generation. Impressively, inactivation of <i>smdK</i> leads to a new carboxylate analogue unveiling a new mechanism for polyketide terminal diene formation

Identification of the Grincamycin Gene Cluster Unveils Divergent Roles for GcnQ in Different Hosts, Tailoring the l‑Rhodinose Moiety

The gene cluster responsible for grincamycin (GCN, <b>1</b>) biosynthesis in <i>Streptomyces lusitanus</i> SCSIO LR32 was identified; heterologous expression of the GCN cluster in <i>S. coelicolor</i> M512 yielded P-1894B (<b>1b</b>) as a predominant product. The <i>ΔgcnQ</i> mutant accumulates intermediate <b>1a</b> and two shunt products <b>2a</b> and <b>3a</b> bearing l-rhodinose for l-cinerulose A substitutions. In vitro data demonstrated that GcnQ is capable of iteratively tailoring the two l-rhodinose moieties into l-aculose moieties, supporting divergent roles of GcnQ in different hosts

Δ^11,12 Double Bond Formation in Tirandamycin Biosynthesis is Atypically Catalyzed by TrdE, a Glycoside Hydrolase Family Enzyme

The tirandamycins (TAMs) are a small group of Streptomyces-derived natural products that target bacterial RNA polymerase. Within the TAM biosynthetic cluster, <i>trdE</i> encodes a glycoside hydrolase whose role in TAM biosynthesis has been undefined until now. We report that in vivo <i>trdE</i> inactivation leads to accumulation of pre-tirandamycin, the earliest intermediate released from its mixed polyketide/nonribosomal peptide biosynthetic assembly line. In vitro and site-directed mutagenesis studies showed that TrdE, a putative glycoside hydrolase, catalyzes in a highly atypical fashion the installation of the Δ^11,12 double bond during TAM biosynthesis

Halogenated Anthraquinones from the Marine-Derived Fungus <i>Aspergillus</i> sp. SCSIO F063

Metabolomic investigations focusing on the marine-derived fungus <i>Aspergillus</i> sp. SCSIO F063 have unveiled seven new chlorinated anthraquinones (<b>1</b>–<b>7</b>) related to averantin, together with five known analogues (<b>11</b>–<b>15</b>) when the fungus was fermented using sea salt-containing potato dextrose broth. Through the addition of sodium bromide to the broth, two new brominated anthraquinones (<b>8</b>, <b>9</b>) and one new nonhalogenated anthraquinone (<b>10</b>) were obtained from the fungal mycelia. Their structures were elucidated by extensive spectroscopic analyses including MS and 1D and 2D NMR data. One metabolite, 6-<i>O</i>-methyl-7-chloroaveratin (<b>2</b>), displayed inhibition activity against three human tumor cell lines, SF-268, MCF-7, and NCI-H460, with IC₅₀ values of 7.11, 6.64, and 7.42 μM, respectively

Cytotoxic and Antibacterial Marfuraquinocins from the Deep South China Sea-Derived Streptomyces niveus SCSIO 3406

Four new sesquiterpenoid naphthoquinones, marfuraquinocins A–D (<b>1</b>–<b>4</b>), and two new geranylated phenazines, phenaziterpenes A (<b>5</b>) and B (<b>6</b>), were isolated from the fermentation broth of Streptomyces niveus SCSIO 3406, which originated from a South China Sea sediment sample obtained from a depth of 3536 m. The structures of <b>1</b>–<b>6</b> were elucidated on the basis of extensive MS and one-dimensional and two-dimensional NMR spectroscopic analyses. In a panel of cytotoxicity and antibacterial assays, <b>1</b> and <b>3</b> were found to inhibit a NCI-H460 cancer cell line with IC₅₀ values of 3.7 and 4.4 μM, respectively. Compounds <b>1</b>, <b>3</b>, and <b>4</b> exhibited antibacterial activities against Staphylococcus aureus ATCC 29213 with equivalent MIC values of 8.0 μg/mL; compounds <b>3</b> and <b>4</b> each showed antibacterial activity against methicillin-resistant Staphylococcus epidermidis (MRSE) shhs-E1 with MIC values of 8.0 μg/mL

Abyssomicin Monomers and Dimers from the Marine-Derived <i>Streptomyces koyangensis</i> SCSIO 5802

Three new abyssomicin monomers designated neoabyssomicins D (<b>1</b>), E (<b>2</b>), and A2 (<b>3</b>) and the two dimeric neoabyssomicins F (<b>4</b>) and G (<b>5</b>) were discovered from the marine-derived <i>Streptomyces koyangensis</i> SCSIO 5802, and their structures rigorously elucidated. Neoabyssomicin D (<b>1</b>) possesses an unprecedented 8/5/5/7 ring skeleton, the biosynthesis of which (as well as <b>2</b>) is proposed herein. Additionally, dimeric agents <b>4</b> and <b>5</b> were found to be active against methicillin-resistant <i>Staphylococcus aureus</i> and vesicular stomatitis virus, respectively

Abyssomicin Monomers and Dimers from the Marine-Derived <i>Streptomyces koyangensis</i> SCSIO 5802

Three new abyssomicin monomers designated neoabyssomicins D (<b>1</b>), E (<b>2</b>), and A2 (<b>3</b>) and the two dimeric neoabyssomicins F (<b>4</b>) and G (<b>5</b>) were discovered from the marine-derived <i>Streptomyces koyangensis</i> SCSIO 5802, and their structures rigorously elucidated. Neoabyssomicin D (<b>1</b>) possesses an unprecedented 8/5/5/7 ring skeleton, the biosynthesis of which (as well as <b>2</b>) is proposed herein. Additionally, dimeric agents <b>4</b> and <b>5</b> were found to be active against methicillin-resistant <i>Staphylococcus aureus</i> and vesicular stomatitis virus, respectively