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

2009 ◽  
Vol 75 (9) ◽  
pp. 2958-2963 ◽  
Author(s):  
Wei Li ◽  
ShenChieh Chou ◽  
Ankush Khullar ◽  
Barbara Gerratana

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.

2019 ◽  
Vol 17 (3) ◽  
pp. 461-466 ◽  
Author(s):  
Taro Shiraishi ◽  
Makoto Nishiyama ◽  
Tomohisa Kuzuyama

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


2019 ◽  
Author(s):  
Wenqing Zhou ◽  
Haoyu Liang ◽  
Xiangjing Qin ◽  
Danfeng Cao ◽  
Xiangcheng Zhu ◽  
...  

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 (<b>3</b>) and pyrroloformamide D (<b>4</b>), were isolated from <i>Streptomyces </i>sp. CB02980, together with the known pyrroloformamides <b>1 </b>and <b>2</b>. The biosynthetic gene cluster for pyrroloformamides was identified from <i>S</i>. 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 <b>1</b>-<b>4</b>. Overexpression of <i>pyfN</i>, a type II thioesterase gene, increased the production of <b>1</b> and <b>2</b>. The structure elucidation and biosynthetic characterization of pyrroloformamides <b>1</b> - <b>4</b> may inspire future efforts to discover new dithiolopyrrolones, which are promising drug leads for the treatment of infectious diseases or cancer.


2020 ◽  
Vol 117 (19) ◽  
pp. 10265-10270
Author(s):  
Daan Ren ◽  
Mark W. Ruszczycky ◽  
Yeonjin Ko ◽  
Shao-An Wang ◽  
Yasushi Ogasawara ◽  
...  

Coformycin and pentostatin are structurally related N-nucleoside inhibitors of adenosine deaminase characterized by an unusual 1,3-diazepine nucleobase. Herein, the cof gene cluster responsible for coformycin biosynthesis is identified. Reconstitution of the coformycin biosynthetic pathway in vitro demonstrates that it overlaps significantly with the early stages of l-histidine biosynthesis. Committed entry into the coformycin pathway takes place via conversion of a shared branch point intermediate to 8-ketocoformycin-5′-monophosphate catalyzed by CofB, which is a homolog of succinylaminoimidazolecarboxamide ribotide (SAICAR) synthetase. This reaction appears to proceed via a Dieckmann cyclization and a retro-aldol elimination, releasing ammonia and D-erythronate-4-phosphate as coproducts. Completion of coformycin biosynthesis involves reduction and dephosphorylation of the CofB product, with the former reaction being catalyzed by the NADPH-dependent dehydrogenase CofA. CofB also shows activation by adenosine triphosphate (ATP) despite the reaction requiring neither a phosphorylated nor an adenylated intermediate. This may serve to help regulate metabolic partitioning between the l-histidine and coformycin pathways.


2019 ◽  
Author(s):  
Wenqing Zhou ◽  
Haoyu Liang ◽  
Xiangjing Qin ◽  
Danfeng Cao ◽  
Xiangcheng Zhu ◽  
...  

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 (<b>3</b>) and pyrroloformamide D (<b>4</b>), were isolated from <i>Streptomyces </i>sp. CB02980, together with the known pyrroloformamides <b>1 </b>and <b>2</b>. The biosynthetic gene cluster for pyrroloformamides was identified from <i>S</i>. 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 <b>1</b>-<b>4</b>. Overexpression of <i>pyfN</i>, a type II thioesterase gene, increased the production of <b>1</b> and <b>2</b>. The structure elucidation and biosynthetic characterization of pyrroloformamides <b>1</b> - <b>4</b> may inspire future efforts to discover new dithiolopyrrolones, which are promising drug leads for the treatment of infectious diseases or cancer.


Gene ◽  
2001 ◽  
Vol 278 (1-2) ◽  
pp. 107-114 ◽  
Author(s):  
Antonella Morea ◽  
Kalai Mathee ◽  
Michael J. Franklin ◽  
Alessio Giacomini ◽  
Michael O'Regan ◽  
...  

Gene ◽  
1990 ◽  
Vol 90 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Danila Limauro ◽  
Alessandra Avitabile ◽  
Carmela Cappellano ◽  
Anna Maria Puglia ◽  
Carmelo B. Bruni

2002 ◽  
Vol 267 (5) ◽  
pp. 636-646 ◽  
Author(s):  
Y. Abe ◽  
T. Suzuki ◽  
C. Ono ◽  
K. Iwamoto ◽  
M. Hosobuchi ◽  
...  

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