Genome Mining Coupled with OSMAC-Based Cultivation Reveal Differential Production of Surugamide A by the Marine Sponge Isolate Streptomyces sp. SM17 When Compared to Its Terrestrial Relative S. albidoflavus J1074

Much recent interest has arisen in investigating Streptomyces isolates derived from the marine environment in the search for new bioactive compounds, particularly those found in association with marine invertebrates, such as sponges. Among these new compounds recently identified from marine Streptomyces isolates are the octapeptidic surugamides, which have been shown to possess anticancer and antifungal activities. By employing genome mining followed by an one strain many compounds (OSMAC)-based approach, we have identified the previously unreported capability of a marine sponge-derived isolate, namely Streptomyces sp. SM17, to produce surugamide A. Phylogenomics analyses provided novel insights on the distribution and conservation of the surugamides biosynthetic gene cluster (sur BGC) and suggested a closer relatedness between marine-derived sur BGCs than their terrestrially derived counterparts. Subsequent analysis showed differential production of surugamide A when comparing the closely related marine and terrestrial isolates, namely Streptomyces sp. SM17 and Streptomyces albidoflavus J1074. SM17 produced higher levels of surugamide A than S. albidoflavus J1074 under all conditions tested, and in particular producing >13-fold higher levels when grown in YD and 3-fold higher levels in SYP-NaCl medium. In addition, surugamide A production was repressed in TSB and YD medium, suggesting that carbon catabolite repression (CCR) may influence the production of surugamides in these strains.

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Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New Polycyclic Tetramate Macrolactams

Marine Drugs ◽

10.3390/md17120663 ◽

2019 ◽

Vol 17 (12) ◽

pp. 663 ◽

Cited By ~ 4

Author(s):

Wei Liu ◽

Wenjun Zhang ◽

Hongbo Jin ◽

Qingbo Zhang ◽

Yuchan Chen ◽

...

Keyword(s):

Gene Cluster ◽

Genome Mining ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Trans Orientation ◽

Streptomyces Species ◽

Streptomyces Sp ◽

Isolation And Characterization ◽

Planar Structures ◽

Ic50 Values

Polycyclic tetramate macrolactams (PTMs) biosynthetic gene cluster are widely distributed in different bacterial types, especially in Streptomyces species. The mining of the genomic data of marine-derived Streptomyces sp. SCSIO 40010 reveals the presence of a putative PTM-encoding biosynthetic gene cluster (ptm′ BGC) that features a genetic organization for potentially producing 5/5/6 type of carbocyclic ring-containing PTMs. A fermentation of Streptomyces sp. SCSIO 40010 led to the isolation and characterization of six new PTMs 1–6. Comprehensive spectroscopic analysis assigned their planar structures and relative configurations, and their absolute configurations were deduced by comparing the experimental electronic circular dichroism (ECD) spectra with the reported spectra of the known PTMs. Intriguingly, compounds 1–6 were determined to have a trans-orientation of H-10/H-11 at the first 5-membered ring, being distinct from the cis-orientation in their known PTM congeners. PTMs 1–5 displayed cytotoxicity against several cancer cell lines, with IC50 values that ranged from 2.47 to 17.68 µM.

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Identification of the kinanthraquinone biosynthetic gene cluster by expression of an atypical response regulator

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa082 ◽

2021 ◽

Vol 85 (3) ◽

pp. 714-721

Author(s):

Risa Takao ◽

Katsuyuki Sakai ◽

Hiroyuki Koshino ◽

Hiroyuki Osada ◽

Shunji Takahashi

Keyword(s):

Heterologous Expression ◽

Gene Cluster ◽

Secondary Metabolite ◽

Response Regulator ◽

Bac Library ◽

Gene Clusters ◽

Biosynthetic Gene Cluster ◽

Gene Organization ◽

Biosynthetic Gene ◽

Streptomyces Sp

ABSTRACT Recent advances in genome sequencing have revealed a variety of secondary metabolite biosynthetic gene clusters in actinomycetes. Understanding the biosynthetic mechanism controlling secondary metabolite production is important for utilizing these gene clusters. In this study, we focused on the kinanthraquinone biosynthetic gene cluster, which has not been identified yet in Streptomyces sp. SN-593. Based on chemical structure, 5 type II polyketide synthase gene clusters were listed from the genome sequence of Streptomyces sp. SN-593. Among them, a candidate gene cluster was selected by comparing the gene organization with grincamycin, which is synthesized through an intermediate similar to kinanthraquinone. We initially utilized a BAC library for subcloning the kiq gene cluster, performed heterologous expression in Streptomyces lividans TK23, and identified the production of kinanthraquinone and kinanthraquinone B. We also found that heterologous expression of kiqA, which belongs to the DNA-binding response regulator OmpR family, dramatically enhanced the production of kinanthraquinones.

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Discovery of a Potential Liver Fibrosis Inhibitor from a Mushroom Endophytic Fungus by Genome Mining of a Silent Biosynthetic Gene Cluster

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.1c03639 ◽

2021 ◽

Vol 69 (38) ◽

pp. 11303-11310

Author(s):

Jin-Tao Cheng ◽

Han-Min Wang ◽

Jia-Hui Yu ◽

Chen-Fan Sun ◽

Fei Cao ◽

...

Keyword(s):

Liver Fibrosis ◽

Gene Cluster ◽

Endophytic Fungus ◽

Genome Mining ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene

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Draft Genome Sequence of Streptomyces sp. TP-A0874, a Catechoserine Producer

Genome Announcements ◽

10.1128/genomea.01163-16 ◽

2016 ◽

Vol 4 (5) ◽

Author(s):

Hisayuki Komaki ◽

Akira Hosoyama ◽

Natsuko Ichikawa ◽

Yasuhiro Igarashi

Keyword(s):

Genome Sequence ◽

Cell Invasion ◽

Draft Genome ◽

Gene Clusters ◽

Bioinformatic Analysis ◽

Biosynthetic Gene Cluster ◽

Tumor Cell Invasion ◽

Draft Genome Sequence ◽

Biosynthetic Gene ◽

Streptomyces Sp

We report the draft genome sequence of Streptomyces sp. TP-A0874 isolated from compost. This strain produces catechoserine, a new catecholate-type inhibitor of tumor cell invasion. The genome harbors at least six gene clusters for polyketide and nonribosomal peptide biosyntheses. The biosynthetic gene cluster for catechoserines was identified by bioinformatic analysis.

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Isolation of the biosynthetic gene cluster for tautomycetin, a linear polyketide T cell-specific immunomodulator from Streptomyces sp. CK4412

Microbiology ◽

10.1099/mic.0.2006/003194-0 ◽

2007 ◽

Vol 153 (4) ◽

pp. 1095-1102 ◽

Cited By ~ 29

Author(s):

Si-Sun Choi ◽

Yoon-Ah Hur ◽

David H Sherman ◽

Eung-Soo Kim

Keyword(s):

T Cell ◽

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Streptomyces Sp

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Bioactive Molecules from Mangrove Streptomyces qinglanensis 172205

Marine Drugs ◽

10.3390/md18050255 ◽

2020 ◽

Vol 18 (5) ◽

pp. 255

Author(s):

Dongbo Xu ◽

Erli Tian ◽

Fandong Kong ◽

Kui Hong

Keyword(s):

Gene Cluster ◽

Secondary Metabolite ◽

Biosynthetic Gene Cluster ◽

Bioactive Molecules ◽

Spectroscopic Methods ◽

Biosynthetic Gene ◽

Electronic Circular Dichroism ◽

Chemical Structures ◽

New Compounds ◽

Antiproliferative Activities

Five new compounds 15R-17,18-dehydroxantholipin (1), (3E,5E,7E)-3-methyldeca-3,5,7-triene-2,9-dione (2) and qinlactone A–C (3–5) were identified from mangrove Streptomyces qinglanensis 172205 with “genetic dereplication,” which deleted the highly expressed secondary metabolite-enterocin biosynthetic gene cluster. The chemical structures were established by spectroscopic methods, and the absolute configurations were determined by electronic circular dichroism (ECD). Compound 1 exhibited strong anti-microbial and antiproliferative bioactivities, while compounds 2–4 showed weak antiproliferative activities.

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Isolation and characterization of meridamycin biosynthetic gene cluster from Streptomyces sp. NRRL 30748

Gene ◽

10.1016/j.gene.2006.03.021 ◽

2006 ◽

Vol 377 ◽

pp. 109-118 ◽

Cited By ~ 16

Author(s):

Min He ◽

Bradley Haltli ◽

Mia Summers ◽

Xidong Feng ◽

John Hucul

Keyword(s):

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Streptomyces Sp ◽

Isolation And Characterization

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Activation and Characterization of Bohemamine Biosynthetic Gene Cluster from Streptomyces sp. CB02009

Organic Letters ◽

10.1021/acs.orglett.0c01224 ◽

2020 ◽

Vol 22 (12) ◽

pp. 4614-4619 ◽

Cited By ~ 2

Author(s):

Ling Liu ◽

Sainan Li ◽

Runze Sun ◽

Xiangjing Qin ◽

Jianhua Ju ◽

...

Keyword(s):

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Streptomyces Sp

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Genomic analysis of siderophore β-hydroxylases reveals divergent stereocontrol and expands the condensation domain family

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1903161116 ◽

2019 ◽

Vol 116 (40) ◽

pp. 19805-19814 ◽

Cited By ~ 8

Author(s):

Zachary L. Reitz ◽

Clifford D. Hardy ◽

Jaewon Suk ◽

Jean Bouvet ◽

Alison Butler

Keyword(s):

Predictive Power ◽

Genome Mining ◽

Genomic Analysis ◽

Gene Clusters ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Peptide Synthetase ◽

Condensation Domain

Genome mining of biosynthetic pathways streamlines discovery of secondary metabolites but can leave ambiguities in the predicted structures, which must be rectified experimentally. Through coupling the reactivity predicted by biosynthetic gene clusters with verified structures, the origin of the β-hydroxyaspartic acid diastereomers in siderophores is reported herein. Two functional subtypes of nonheme Fe(II)/α-ketoglutarate–dependent aspartyl β-hydroxylases are identified in siderophore biosynthetic gene clusters, which differ in genomic organization—existing either as fused domains (IβHAsp) at the carboxyl terminus of a nonribosomal peptide synthetase (NRPS) or as stand-alone enzymes (TβHAsp)—and each directs opposite stereoselectivity of Asp β-hydroxylation. The predictive power of this subtype delineation is confirmed by the stereochemical characterization of β-OHAsp residues in pyoverdine GB-1, delftibactin, histicorrugatin, and cupriachelin. The l-threo (2S, 3S) β-OHAsp residues of alterobactin arise from hydroxylation by the β-hydroxylase domain integrated into NRPS AltH, while l-erythro (2S, 3R) β-OHAsp in delftibactin arises from the stand-alone β-hydroxylase DelD. Cupriachelin contains both l-threo and l-erythro β-OHAsp, consistent with the presence of both types of β-hydroxylases in the biosynthetic gene cluster. A third subtype of nonheme Fe(II)/α-ketoglutarate–dependent enzymes (IβHHis) hydroxylates histidyl residues with l-threo stereospecificity. A previously undescribed, noncanonical member of the NRPS condensation domain superfamily is identified, named the interface domain, which is proposed to position the β-hydroxylase and the NRPS-bound amino acid prior to hydroxylation. Through mapping characterized β-OHAsp diastereomers to the phylogenetic tree of siderophore β-hydroxylases, methods to predict β-OHAsp stereochemistry in silico are realized.

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