alexa Identification, Activation And Engineering Production Of The Antitumor UCS1025A
ISSN 2472-1042

Pharmacoeconomics: Open Access
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11th World Congress on Pharmaceutical Sciences and Innovations in Pharma Industry
February 27-28, 2017 Amsterdam, Netherlands

Sameh Soliman
University of Sharjah, UAE
University of California, USA
Posters & Accepted Abstracts: Pharmacoeconomics
DOI: 10.4172/2472-1042.C1.003
Abstract
UCS1025A is a novel polyketide-non-ribosomal peptide (PK-NRP) hybrid fungal metabolite with a decalin-like structure. UCS1025A isolated from Acremonium fungus KY4917 (FERM) and exhibiting antibacterial and antiproliferative activities. Although it is known for a decade, its biosynthesis has not been elucidated. The gene cluster for USC1025A was predicted by bioinformatics analysis and its PKS-NRPS deletion mutation validates its essential role in UCS1025A biosynthesis. Heterogonous engineering of the gene cluster into Aspergillus nidulans using yeast recombination-based cloning strategy was successfully performed. Only the gene cluster transformed without transcription factors (AN#2) was able to produce the compound. Activation of the UCS1025A gene cluster in the FERM fungus by over-expressing each transcription factor separately increased the compound production up to 4 times. Similarly activation of the gene cluster in A. nidulans transformed with the UCS1025A gene cluster containing transcription factors (AN#1) was able to detect affordable amount. Two transcription factors would work as activator and one as repressor. The UCS1025A gene cluster (1759) with another gene cluster (1590) comprised a branch of a phylogenetic tree close to lovastatin gene cluster indicating similar compound could be produced by this cluster. This work will help in genetic manipulation and investigation of the UCS1025A biosynthetic pathway.
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