Document Detail

Functional modular dissection of DEBS1-TE changes triketide lactone ratios and provides insight into acyl group loading, hydrolysis, and ACP transfer.
MedLine Citation:
PMID:  23116287     Owner:  NLM     Status:  Publisher    
The DEBS1-TE fusion protein is comprised of the loading module, the first two extension modules, and the terminal TE domain of the Saccharolyspora erythraea 6-deoxyerythronolide B synthase. DEBS1-TE produces triketide lactones that differ based on the starter unit selected by the loading module. Typical fermentations with plasmid-based expression of DEBS1-TE produce a 6:1 ratio of propionate to isobutyrate-derived triketide lactones. Functional dissection of the loading module from the remainder of DEBS1-TE results in 50% lower titers of triketide lactone and a dramatic shift in the production to a 1:4 ratio of propionate to isobutyrate derived products. A series of radiolabeling studies of the loading module has shown that transfer from the AT to the ACP occurs much faster for propionate than for isobutyrate. However, the equilibrium occupancy of the AT favors isobutyrate such that propionate is outcompeted for ACP occupancy. Thus propionyl-ACP is the kinetic product while isobutyryl-ACP is the thermodynamic product. A slowed transfer from the loading domain ACP to first extension module KS due to functional dissection of DEBS1-TE allows this isobutyryl-ACP favored equilibrium to be realized and likely accounts for the observed shift in triketide lactone products.
John Yan; Christopher Hazzard; Shilah A Bonnett; Kevin A Reynolds
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-1
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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