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Fungal Polyketide Synthase Product Chain-Length Control by Partnering Thiohydrolase

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...[Show more]

dc.contributor.authorZabala, Angelica O.
dc.contributor.authorChooi, Yit-Heng
dc.contributor.authorChoi, Moon Seok
dc.contributor.authorLin, Hsiao-Ching
dc.contributor.authorTang, Yi
dc.date.accessioned2015-12-13T22:27:56Z
dc.identifier.issn1554-8929
dc.identifier.urihttp://hdl.handle.net/1885/74171
dc.description.abstractFungal 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.
dc.publisherAmerican Chemical Society
dc.sourceACS chemical biology
dc.titleFungal Polyketide Synthase Product Chain-Length Control by Partnering Thiohydrolase
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume9
dc.date.issued2014
local.identifier.absfor060107 - Enzymes
local.identifier.ariespublicationU3488905xPUB3996
local.type.statusPublished Version
local.contributor.affiliationZabala, Angelica O., University of California
local.contributor.affiliationChooi, Yit-Heng, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChoi, Moon Seok, University of California
local.contributor.affiliationLin, Hsiao-Ching, University of California
local.contributor.affiliationTang, Yi, University of California
local.description.embargo2037-12-31
local.bibliographicCitation.issue7
local.bibliographicCitation.startpage1576
local.bibliographicCitation.lastpage1586
local.identifier.doi10.1021/cb500284t
local.identifier.absseo860803 - Human Pharmaceutical Treatments (e.g. Antibiotics)
dc.date.updated2015-12-11T08:35:52Z
local.identifier.scopusID2-s2.0-84904576107
local.identifier.thomsonID000339366600024
CollectionsANU Research Publications

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