Identification, activation and engineering production of the antitumor UCS1025A

11^th 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

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.

Biography :

Email: ssoliman@sharjah.ac.ae