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Accessing new chemical diversity from ancient non‐actinobacterial strains
Author(s) -
Terrell Stephanie M.,
Wu Yang,
Klein Joshua G.,
Charkoudian Louise K.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.656.21
Subject(s) - polyketide , computational biology , escherichia coli , biology , phylum , synthetic biology , gene , small molecule , identification (biology) , biosynthesis , biochemistry , heterologous expression , heterologous , in vitro , genetics , chemistry , recombinant dna , botany
Our work focuses on the discovery of new biosynthetic routes to chemical diversity through the characterization of unexplored polyketide synthase (PKS) gene clusters and enzymes from ancient and diverse phyla. In the first part of this work, two ancient non‐actinobacterial organisms were cultured, and their secondary metabolites extracted, fractionated, and characterized by liquid chromatography mass spectrometry (LC‐MS) in the search for novel molecules and biosynthetic pathways. These data are currently being compared to existing molecular networks in order to identify novel molecules. In a second part of this work, ancient non‐actinobacterial strains are being evaluated as a source of PKS enzymes that can be expressed in tractable heterologous hosts to enable in vitro characterization of poorly‐understood PKSs. We have successfully expressed a ketosynthase‐chain length factor (KS‐CLF) heterodimer pair, which is essential in the manufacturing of polyaromatic polyketides, in Escherichia coli , and are currently evaluating its activity in vitro . Results from these studies are expected to lead to the identification of new chemical diversity encoded by nature, as well as novel tools to enable the biosynthetic engineering of hybrid PKSs. Support or Funding Information We would like to acknowledge an NSF CAREER Award #R15GM120704 to Louise K. Charkoudian as a source of funding for this project. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .