Elucidating the Sugar Tailoring Steps in the Cytorhodin Biosynthetic Pathway

Anthracycline antitumor cytorhodins X and Y feature a rare 9α-glycoside and 7-dexoy-aglycone. Characterization of the cytorhodin gene cluster from <i>Streptomyces</i> sp. SCSIO 1666 through gene inactivations and metabolite analyses reveals three glycosyltransferases (GTs) involved in the sugar tailoring steps. The duo of CytG1 and CytL effects C-7 glycosylation with l-rhodosamine whereas the iterative GT CytG3 and CytW similarly modifies both C-9 and C-10 positions. CytG2 also acts iteratively by incorporating the second and third sugar moiety into the trisaccharide chains at the C-7 or C-10 position

MOESM1 of Identification and utilization of two important transporters: SgvT1 and SgvT2, for griseoviridin and viridogrisein biosynthesis in Streptomyces griseoviridis

Additional file 1: Figure S1. The multiple alignment of SgvT1/T3 with other transporters. Figure S2. The multiple alignment of SgvT2 with other transporters. Figures S3–S5. The inactivation of sgvT1-T3. Figure S6–S8. HPLC analyses of the fermentation extract of Wild-type & ΔsgvT1-T3. Figure S9. HPLC analyses of the fermentation extract of WT::sgvT1–T2. Figure S10. The HPLC standard curve of GV/ VG. Figure S11. HPLC analyses of fermentation extract of complemented mutants. Table S1. Primer pairs used for PCR-targeting of sgvT1–T3. Table S2. Primers used for PCR confirmation of double-crossover mutants. Table S3. Primer pairs used for complementation of sgvT1–T3. Table S4. Primer pairs used for RT-PCR. Table S5. Primer pairs used for qPCR. Table S6. Quantitative analysis of GV/VG production

A new diketopiperazine derivative from a deep sea-derived <i>Streptomyces</i> sp. SCSIO 04496

<div><p>A new diketopiperazine (DKP) derivative, (6<i>R</i>,3<i>Z</i>)-3-benzylidene-6-isobutyl-1-methyl piperazine-2,5-dione (<b>1</b>), as well as five known DKPs <b>2</b>–<b>6</b> was isolated from a deep sea-derived <i>Streptomyces</i> sp. SCSIO 04496. The structure of <b>1</b> was elucidated using a combination of 1D and 2D NMR, HR-ESI-MS and chiral-phase HPLC techniques. Compounds <b>1</b>–<b>6</b> did not show cytotoxic activity at a concentration of 100 μM in bioactivity assay.</p></div

Discovery of a New Family of Dieckmann Cyclases Essential to Tetramic Acid and Pyridone-Based Natural Products Biosynthesis

Bioinformatic analyses indicate that TrdC, SlgL, LipX₂, KirHI, and FacHI belong to a group of highly homologous proteins involved in biosynthesis of actinomycete-derived tirandamycin B, streptolydigin, α-lipomycin, kirromycin, and factumycin, respectively. However, assignment of their biosynthetic roles has remained elusive. Gene inactivation and complementation, <i>in vitro</i> biochemical assays with synthetic analogues, point mutations, and phylogenetic tree analyses reveal that these proteins represent a new family of Dieckmann cyclases that drive tetramic acid and pyridone scaffold biosynthesis

MOESM1 of Overexpression of a type III PKS gene affording novel violapyrones with enhanced anti-influenza A virus activity

Additional file 1: Table S1. Plasmids and strains used in this study. Table S2. Primer pairs used in this study. Table S3. Homologous locus of vioAB in different Streptomyces genomes. Figure S1. Relative yields for compounds 1–14 in different strains. Figure S2. Spectral data of 1. Figure S3. Spectral data of 2. Figure S4. Spectral data of 3. Figure S5. Spectral data of 4. Figure S6. Spectral data of 5. Figure S7. Spectral data of 6. Figure S8. Spectral data of 7. Figure S9. Spectral data of 8. Figure S10. Spectral data of 9. Figure S11. Spectral data of 10. Figure S12. Spectral data of 11. Figure S13. Spectral data of 12. Figure S14. Spectral data of 13. Figure S15. Spectral data of 14. Figure S16. Multiple-sequence alignments of VioA with selected type III PKSs. Figure S17. Site-directed mutagenesis study of VioA

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

Enzymatic Synthesis of GDP-α‑l‑fucofuranose by MtdL and Hyg20

Two mutases, MtdL and Hyg20, are reported. Both are able to functionally drive the biosynthesis of GDP-α-l-fucofuranose. Both enzymes catalyze similar functions, catalytically enabling the bidirectional reaction between GDP-β-l-fucopyranose and GDP-α-l-fucofuranose using only divalent cations as cofactors. This realization is but one of a number of important insights into fucofuranose biosynthesis presented herein

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

Post-Polyketide Synthase Steps in Iso-migrastatin Biosynthesis, Featuring Tailoring Enzymes with Broad Substrate Specificity

The iso-migrastatin (iso-MGS) bio­synthetic gene cluster from <i>Strepto­myces platensis</i> NRRL 18993 consists of 11 genes, featuring an acyl­transferase (AT)-less type I poly­ketide synthase (PKS) and three tailoring enzymes MgsIJK. Systematic inactivation of <i>mgsIJK</i> in <i>S. platensis</i> enabled us to (i) identify two nascent products of the iso-MGS AT-less type I PKS, establishing an unprecedented novel feature for AT-less type I PKSs, and (ii) account for the formation of all known post-PKS bio­synthetic intermediates generated by the three tailoring enzymes MgsIJK, which possessed significant substrate promiscuities