The Isolation of Pyrroloformamide Congeners and Characterization of Its Biosynthetic Gene Cluster from Streptomyces sp. CB02980 Revealed a Unified Mechanism for Dithiolopyrrolone Biosynthesis

Dithiolopyrrolones are microbial natural products containing a disulfide or thiosulfonate bridge embedded in a unique bicyclic structure. In the current study, two new dithiolopyrrolones, pyrroloformamide C (3) and pyrroloformamide D (4), were isolated from Streptomyces sp. CB02980, together with the known pyrroloformamides 1 and 2. The biosynthetic gene cluster for pyrroloformamides was identified from S. sp. CB02980, which shared high sequence similarity with those of dithiolopyrrolones, including holomycin and thiolutin. Gene replacement of pyfE, which encodes a non-ribosomal peptide synthetase, abolished the production of 1－4. Overexpression of pyfN, a type II thioesterase gene, increased the production of 1 and 2. The structure elucidation and biosynthetic characterization of pyrroloformamides 1 - 4 may inspire future efforts to discover new dithiolopyrrolones, which are promising drug leads for the treatment of infectious diseases or cancer.

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The Isolation of Pyrroloformamide Congeners and Characterization of Its Biosynthetic Gene Cluster from Streptomyces sp. CB02980 Revealed a Unified Mechanism for Dithiolopyrrolone Biosynthesis

10.26434/chemrxiv.10208717 ◽

2019 ◽

Author(s):

Wenqing Zhou ◽

Haoyu Liang ◽

Xiangjing Qin ◽

Danfeng Cao ◽

Xiangcheng Zhu ◽

...

Keyword(s):

Gene Cluster ◽

Sequence Similarity ◽

Biosynthetic Gene Cluster ◽

Gene Replacement ◽

Biosynthetic Gene ◽

High Sequence Similarity ◽

Bicyclic Structure ◽

Microbial Natural Products ◽

Drug Leads

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Cloning and Characterization of the Biosynthetic Gene Cluster for Tomaymycin, an SJG-136 Monomeric Analog

Applied and Environmental Microbiology ◽

10.1128/aem.02325-08 ◽

2009 ◽

Vol 75 (9) ◽

pp. 2958-2963 ◽

Cited By ~ 65

Author(s):

Wei Li ◽

ShenChieh Chou ◽

Ankush Khullar ◽

Barbara Gerratana

Keyword(s):

Cluster Analysis ◽

Gene Cluster ◽

Biosynthetic Pathway ◽

Biosynthetic Gene Cluster ◽

Gene Replacement ◽

Biosynthetic Gene

ABSTRACT Tomaymycin produced by Streptomyces achromogenes is a naturally produced pyrrolobenzodiazepine (PBD). The biosynthetic gene cluster for tomaymycin was identified and sequenced. The gene cluster analysis reveals a novel biosynthetic pathway for the anthranilate moiety of PBDs. Gene replacement and chemical complementation studies were used to confirm the proposed biosynthetic pathway.

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Faculty Opinions recommendation of Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718199368.793490454 ◽

2014 ◽

Author(s):

Jason Crawford

Keyword(s):

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene

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Identification and Characterization of the Biosynthetic Gene Cluster of Thiolutin, a Tumor Angiogenesis Inhibitor, in Saccharothrix algeriensis NRRL B-24137

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520614666141027145200 ◽

2015 ◽

Vol 15 (3) ◽

pp. 277-284 ◽

Cited By ~ 9

Author(s):

Sheng Huang ◽

Ming Tong ◽

Zhiwei Qin ◽

Zixin Deng ◽

Hai Deng ◽

...

Keyword(s):

Gene Cluster ◽

Tumor Angiogenesis ◽

Angiogenesis Inhibitor ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Identification And Characterization

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Characterization of algG encoding C5-epimerase in the alginate biosynthetic gene cluster of Pseudomonas fluorescens

Gene ◽

10.1016/s0378-1119(01)00685-0 ◽

2001 ◽

Vol 278 (1-2) ◽

pp. 107-114 ◽

Cited By ~ 12

Author(s):

Antonella Morea ◽

Kalai Mathee ◽

Michael J. Franklin ◽

Alessio Giacomini ◽

Michael O'Regan ◽

...

Keyword(s):

Pseudomonas Fluorescens ◽

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene

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Cloning and characterization of the histidine biosynthetic gene cluster of Streptomyces coelicolor A3(2)

Gene ◽

10.1016/0378-1119(90)90436-u ◽

1990 ◽

Vol 90 (1) ◽

pp. 31-41 ◽

Cited By ~ 22

Author(s):

Danila Limauro ◽

Alessandra Avitabile ◽

Carmela Cappellano ◽

Anna Maria Puglia ◽

Carmelo B. Bruni

Keyword(s):

Gene Cluster ◽

Streptomyces Coelicolor ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene

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Molecular cloning and characterization of an ML-236B (compactin) biosynthetic gene cluster in Penicillium citrinum

Molecular Genetics and Genomics ◽

10.1007/s00438-002-0697-y ◽

2002 ◽

Vol 267 (5) ◽

pp. 636-646 ◽

Cited By ~ 102

Author(s):

Y. Abe ◽

T. Suzuki ◽

C. Ono ◽

K. Iwamoto ◽

M. Hosobuchi ◽

...

Keyword(s):

Molecular Cloning ◽

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Penicillium Citrinum ◽

Biosynthetic Gene

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Genetic localization and in vivo characterization of a Monascus azaphilone pigment biosynthetic gene cluster

Applied Microbiology and Biotechnology ◽

10.1007/s00253-013-4745-9 ◽

2013 ◽

Vol 97 (14) ◽

pp. 6337-6345 ◽

Cited By ~ 79

Author(s):

Bijinu Balakrishnan ◽

Suman Karki ◽

Shih-Hau Chiu ◽

Hyun-Ju Kim ◽

Jae-Won Suh ◽

...

Keyword(s):

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Genetic Localization ◽

In Vivo Characterization ◽

Azaphilone Pigment

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Biosynthesis of the uridine-derived nucleoside antibiotic A-94964: identification and characterization of the biosynthetic gene cluster provide insight into the biosynthetic pathway

Organic & Biomolecular Chemistry ◽

10.1039/c8ob02765j ◽

2019 ◽

Vol 17 (3) ◽

pp. 461-466 ◽

Cited By ~ 5

Author(s):

Taro Shiraishi ◽

Makoto Nishiyama ◽

Tomohisa Kuzuyama

Keyword(s):

Gene Cluster ◽

In Silico ◽

Biosynthetic Pathway ◽

Gene Deletion ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Identification And Characterization ◽

Insight Into

The biosynthetic pathway of the uridine-derived nucleoside antibiotic A-94964 was proposed via in silico analysis coupled with gene deletion experiments.

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