by Partnering Thiohydrolase

Zabala, Angelica; O.; Chooi, Yit-Heng; Choi, Moon Seok; Lin, Hsiao-Ching; Tang, Yi

doi:10.1021/cb500284t

i

by Partnering Thiohydrolase

Supporting Files

May 29 2014
By Zabala, Angelica ; O. ; Chooi, Yit-Heng ; ...

File Language:

English

Details

Alternative Title:

ACS Chem Biol
Personal Author:

Zabala, Angelica ; O. ; Chooi, Yit-Heng ; Choi, Moon Seok ; Lin, Hsiao-Ching ; Tang, Yi
Description:

Fungal highly reducing polyketide synthases (HRPKSs) are an enigmatic group of multidomain enzymes that catalyze the biosynthesis of structurally diverse compounds. This variety stems from their intrinsic programming rules, which permutate the use of tailoring domains and determine the overall number of iterative cycles. From genome sequencing and mining of the producing strain Eupenicillium brefeldianum ATCC 58665, we identified an HRPKS involved in the biosynthesis of an important protein transport-inhibitor Brefeldin A (BFA), followed by reconstitution of its activity in Saccharomyces cerevisiae and in vitro. Bref-PKS demonstrated an NADPH-dependent reductive tailoring specificity that led to the synthesis of four different octaketide products with varying degrees of reduction. Furthermore, contrary to what is expected from the structure of BFA, Bref-PKS is found to be a nonaketide synthase in the absence of an associated thiohydrolase Bref-TH. Such chain-length control by the partner thiohydrolase was found to be present in other HRPKS systems and highlights the importance of including tailoring enzyme activities in predicting fungal HRPKS functions and their products.
Subjects:

Anti-Infective Agents Brefeldin A Cloning, Molecular Eupenicillium Genome, Fungal Hydrolases Molecular Sequence Data Multigene Family Polyketide Synthases Saccharomyces Cerevisiae Transcriptome
Source:

ACS Chem Biol. 2014; 9(7):1576-1586.
Pubmed ID:

24845309
Pubmed Central ID:

PMC4215887
Document Type:

Journal Article
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 ; T32GM067555/GM/NIGMS NIH HHS/United States
Volume:

9
Issue:

7
Collection(s):

CDC Public Access
Main Document Checksum:

urn:sha256:62e307b23c0b6409bc321cbfb5278ff8e8daa67e0e0d17ade1259c46d2c49d25
Download URL:

https://stacks.cdc.gov/view/cdc/31448/cdc_31448_DS1.pdf
File Type:

[PDF - 1.67 MB ]

File Language:

English

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