TY - JOUR

T1 - Three previously unrecognised classes of biosynthetic enzymes revealed during the production of xenovulene A

AU - Schor, Raissa

AU - Schotte, Carsten

AU - Wibberg, Daniel

AU - Kalinowski, Jörn

AU - Cox, Russell J.

N1 - Funding information: We thank DFG (INST 187/621) for LCMS equipment. R.S. and C.S. are funded by The Leibniz Universitat Hannover. The bioinformatics support of the BMBF-funded project Bielefeld-Gieen Center for Microbial Bioinformatics-BiGi (grant number 031A533) within the German Network for Bioinformatics Infrastructure (de.NBI) is gratefully acknowledged. We thank Miriam Streeck and Katja Korner for technical aistance. We thank Clara Oberhauser and Profeor Andreas Kirschning for the gift of FPP and the Leibniz University of Hannover and Institute of Organic Chemistry for financial and technical support We thank DFG (INST 187/621) for LCMS equipment. R.S. and C.S. are funded by The Leibniz Universität Hannover. The bioinformatics support of the BMBF-funded project Bielefeld-Gießen Center for Microbial Bioinformatics-BiGi (grant number 031A533) within the German Network for Bioinformatics Infrastructure (de.NBI) is gratefully acknowledged. We thank Miriam Streeck and Katja Körner for technical assistance. We thank Clara Oberhauser and Professor Andreas Kirschning for the gift of FPP and the Leibniz University of Hannover and Institute of Organic Chemistry for financial and technical support.

PY - 2018/5/17

Y1 - 2018/5/17

N2 - Xenovulene A is a complex fungal meroterpenoid, produced by the organism hitherto known as Acremonium strictum IMI 501407, for which limited biosynthetic evidence exists. Here, we generate a draft genome and show that the producing organism is previously unknown and should be renamed as Sarocladium schorii. A biosynthetic gene cluster is discovered which bears resemblance to those involved in the biosynthesis of fungal tropolones, with additional genes of unknown function. Heterologous reconstruction of the entire pathway in Aspergillus oryzae allows the chemical steps of biosynthesis to be dissected. The pathway shows very limited similarity to the biosynthesis of other fungal meroterpenoids. The pathway features: the initial formation of tropolone intermediates; the likely involvement of a hetero Diels-Alder enzyme; a terpene cyclase with no significant sequence homology to any known terpene cyclase and two enzymes catalysing oxidative-ring contractions.

AB - Xenovulene A is a complex fungal meroterpenoid, produced by the organism hitherto known as Acremonium strictum IMI 501407, for which limited biosynthetic evidence exists. Here, we generate a draft genome and show that the producing organism is previously unknown and should be renamed as Sarocladium schorii. A biosynthetic gene cluster is discovered which bears resemblance to those involved in the biosynthesis of fungal tropolones, with additional genes of unknown function. Heterologous reconstruction of the entire pathway in Aspergillus oryzae allows the chemical steps of biosynthesis to be dissected. The pathway shows very limited similarity to the biosynthesis of other fungal meroterpenoids. The pathway features: the initial formation of tropolone intermediates; the likely involvement of a hetero Diels-Alder enzyme; a terpene cyclase with no significant sequence homology to any known terpene cyclase and two enzymes catalysing oxidative-ring contractions.

UR - http://www.scopus.com/inward/record.url?scp=85047250314&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-04364-9

DO - 10.1038/s41467-018-04364-9

M3 - Article

C2 - 29773797

AN - SCOPUS:85047250314

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 1963

ER -