Putative identification of the usnic acid biosynthetic gene cluster by de novo whole-genome sequencing of a lichen-forming fungus

Fungal Biology
Mona Abdel-HameedJohn L Sorensen

Abstract

To identify the biosynthetic gene cluster responsible for the biosynthesis of the polyketide usnic acid we carried out the de novo genome sequencing of the fungal partner of Cladonia uncialis. This was followed by comprehensive in silico annotation of polyketide synthase (PKS) genes. The biosynthesis of usnic acid requires a non-reducing PKS possessing a carbon methylation (CMeT) domain, a terminal Claisen cyclase (CLC) domain, and an accompanying oxidative enzyme that dimerizes methylphloracetophenone to usnic acid. Of the 32 candidate PKS genes identified in the mycobiont genome, only one was identified as consistent with these biosynthetic requirements. This gene cluster contains two genes encoding a non-reducing PKS and a cytochrome p450, which have been respectively named methylphloracetophenone synthase (MPAS) and methylphloracetophenone oxidase (MPAO). Both mpas and mpao were demonstrated to be transcriptionally active by reverse transcriptase-PCR of the mRNA in a lichen sample that was observed by HPLC to produce usnic acid. Phylogenetic analysis of the bioinformatically identified ketosynthase (KS) and CLC domains of MPAS demonstrated that mpas grouped within a unique clade and that mpas could be used as a phylogenetic...Continue Reading

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Citations

Feb 13, 2016·Natural Product Reports·Marion MillotSophie Tomasi
Jun 7, 2016·Journal of Natural Products·Mona Abdel-HameedJohn L Sorensen
Apr 20, 2016·Mycologia·Mostafa E ElshobaryMichele D Piercey-Normore
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May 29, 2019·The New Phytologist·Veronika KuhnWolfgang Eisenreich
Mar 13, 2020·Genome Biology and Evolution·Bastian Greshake TzovarasIngo Ebersberger
Sep 13, 2018·Journal of Industrial Microbiology & Biotechnology·Robert L Bertrand, John L Sorensen
Jan 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anjuli CalcheraImke Schmitt
Jul 17, 2018·Biochemical and Biophysical Research Communications·Mona E Abdel-HameedJohn L Sorensen
Mar 12, 2021·Genome Biology and Evolution·Gulnara TagirdzhanovaToby Spribille
Jan 15, 2017·Microbiology Spectrum·Martin Grube, Mats Wedin
Feb 28, 2018·Journal of Natural Products·Robert L BertrandJohn L Sorensen
Feb 28, 2018·Journal of Natural Products·Robert L BertrandJohn L Sorensen
Aug 26, 2021·Metabolic Engineering Communications·James T KealeyPhilip J Barr

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