Identification and Characterization of the Chaetoviridin and Chaetomugilin Gene Cluster in Chaetomium globosum Reveals Dual Functions of an Iterative Highly-Reducing Polyketide Synthase

Winter, Jaclyn M.; Sato, Michio; Sugimoto, Satoru; Chiou, Grace; Garg, Neil K.; Tang, Yi; Watanabe, Kenji

doi:10.1021/ja3090498

- Add this to...
- Twitter
- Facebook
- Google Bookmarks
- LinkedIn

Identification and Characterization of the Chaetoviridin and Chaetomugilin Gene Cluster in Chaetomium globosum Reveals Dual Functions of an Iterative Highly-Reducing Polyketide Synthase

Published Date:

Oct 19 2012

Publisher's site:

http://dx.doi.org/10.1021/ja3090498 New Site Icon

Source:

J Am Chem Soc. 134(43):17900-17903.

[PDF - 975.83 KB]

Details:

Personal Authors:

Winter, Jaclyn M. ; Sato, Michio ; Sugimoto, Satoru ; Chiou, Grace ; Garg, Neil K. ; ... More ▼

Keywords:

[+]

Pubmed ID:

23072467

Pubmed Central ID:

PMC3494086

Description:

We report the identification and characterization of the caz biosynthetic cluster from Chaetomium globosum and the characterization of a highly reducing polyketide synthase (PKS) that acts in both a sequential and convergent manner with a nonreducing PKS to form the chaetomugilin and chaetoviridin azaphilones. Genetic inactivation studies verified the involvement of individual caz genes in the biosynthesis of the azaphilones. Through in vitro reconstitution, we demonstrated the in vitro synthesis of chaetoviridin A from the pyranoquinone intermediate cazisochromene using the highly reducing PKS and an acyltransferase.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

1DP1GM106413/DP/NCCDPHP CDC HHS/United States
1R01GM085128/GM/NIGMS NIH HHS/United States
DP1 GM106413/GM/NIGMS NIH HHS/United States
R01 GM085128/GM/NIGMS NIH HHS/United States

Supporting Files:

nihms-416773-f0001.gif	image/gif
nihms-416773-f0001.jpg	image/jpeg
nihms-416773-f0002.gif	image/gif
nihms-416773-f0002.jpg	image/jpeg
nihms-416773-f0003.gif	image/gif
nihms-416773-f0003.jpg	image/jpeg
nihms-416773-f0004.gif	image/gif
nihms-416773-f0004.jpg	image/jpeg
nihms-416773.nxml	text/plain
NIHMS416773-supplement-1_si_001.pdf	application/pdf

No Related Documents.

You May Also Like:

Investigation of fungal iterative polyketide synthase functions using partially assembled intermediates

Personal Author:

Gao, Zhizeng; Wang, Jingjing; Norquay, Amy K.; Qiao, Kangjian; Tang, Yi; Vederas, John C.;

Published:

Jan 28 2013

Source:

J Am Chem Soc. 135(5):1735-1738.

Description:

Iterative polyketide synthases (PKSs) are large, multifunctional enzymes that resemble eukaryotic fatty acid synthases but can make highly functionalized secondary metabolites using complex and unresolved programming rules. During biosynthesis of the...

File Type:

[PDF - 420.78 KB]
Identification and Characterization of the Echinocandin B Biosynthetic Gene Cluster from Emericella rugulosa NRRL 11440

Personal Author:

Cacho, Ralph A.; Jiang, Wei; Chooi, Yit-Heng; Walsh, Christopher T.; Tang, Yi;

Published:

Oct 01 2012

Source:

J Am Chem Soc. 134(40):16781-16790.

Description:

Echinocandins are a family of fungal lipidated cyclic hexapeptide natural products. Due to their effectiveness as antifungal agents, three semisynthetic derivatives have been developed and approved for treatment of human invasive candidiasis. All six...

File Type:

[PDF - 1.60 MB]
Identification and reconstitution of the polyketide synthases responsible for biosynthesis of the anti-malarial agent, cladosporin

Personal Author:

Cochrane, Rachel V. K.; Sanichar, Randy; Lambkin, Gareth R.; Reiz, Béla; Xu, Wei; Tang, Yi; Vederas, John C.;

Published:

Nov 24 2015

Source:

Angew Chem Int Ed Engl. 55(2):664-668.

Description:

The antimalarial agent cladosporin is a nanomolar inhibitor of the Plasmodium falciparum lysyl-tRNA synthetase, and exhibits activity against both blood- and liver-stage infection. Cladosporin can be isolated from the fungus Cladosporium cladosporioi...

File Type:

[PDF - 1.19 MB]
Understanding Programming of Fungal Iterative Polyketide Synthases: the Biochemical Basis for Regioselectivity by the Methyltransferase Domain in the Lovastatin Megasynthase

Personal Author:

Cacho, Ralph A.; Thuss, Justin; Xu, Wei; Sanichar, Randy; Gao, Zhizeng; Nguyen, Allison; Vederas, John C.; Tang, Yi;

Published:

Dec 10 2015

Source:

J Am Chem Soc. 137(50):15688-15691.

Description:

Highly reducing polyketide synthases (HR-PKSs) from fungi synthesize complex natural products using a single set of domains in a highly programmed, iterative fashion. The most enigmatic feature of HR-PKSs is how tailoring domains function selectively...

File Type:

[PDF - 419.13 KB]
Phenalenone Polyketide Cyclization Catalyzed by Fungal Polyketide Synthase and Flavin-Dependent Monooxygenase

Personal Author:

Gao, Shu-Shan; Duan, Abing; Xu, Wei; Yu, Peiyuan; Hang, Leibniz; Houk, K. N.; Tang, Yi;

Published:

Mar 22 2016

Source:

J Am Chem Soc. 138(12):4249-4259.

Description:

Phenalenones are polyketide natural products that display diverse structures and biological activities. The core of phenalenones is a peri-fused tricyclic ring system cyclized from a linear polyketide precursor via an unresolved mechanism. Toward und...

File Type:

[PDF - 2.58 MB]