TY - JOUR

T1 - Strobilurin biosynthesis in Basidiomycete fungi

AU - Nofiani, Risa

AU - de Mattos-Shipley, Kate

AU - Lebe, Karen E.

AU - Han, Li Chen

AU - Iqbal, Zafar

AU - Bailey, Andrew M.

AU - Willis, Christine L.

AU - Simpson, Thomas J.

AU - Cox, Russell J.

N1 - Funding information: R.N. thanks the Directorate General of Resources for Science and Higher Education (Beasiswa Pendidikan Pascasarjana Luar Negeri Direktorat Jenderal Sumber Daya Ilmu Pengetahuan dan Pendidikan Tinggi (BPP-LN Ditjen SD Iptek-Dikti)), Republic of Indonesia, for an Overseas Postgraduate Scholarship and the Alumni foundation of the University of Bristol for financial support. K.d.M.-S. was funded by BBSRC (BB/ K002341/1) and L.-C.H. by BBSRC and EPSRC through BrisSynBio and the Centre for Synthetic Biology (BB/L01386X/1). Z.I. thanks the Higher Education Commission of Pakistan for a post-graduate scholarship. We thank EPSRC (EP/F066104/1) and DFG (INST 187/621–1) for LCMS equipment, BBSRC for culture facilities (BB/L01386X/1) and the University of Bristol Genomics Facility for DNA and RNA sequencing. K.E.L. was funded by the Leibniz University of Hannover. R.J.C. thanks Dr. John Clough and Dr. Katherine Williams for helpful discussions, and Jennifer Senkler (Leibniz Universität) for protein MS analysis.

PY - 2018/9/26

Y1 - 2018/9/26

N2 - Strobilurins from fungi are the inspiration for the creation of the β-methoxyacrylate class of agricultural fungicides. However, molecular details of the biosynthesis of strobilurins have remained cryptic. Here we report the sequence of genomes of two fungi that produce strobilurins and show that each contains a biosynthetic gene cluster, which encodes a highly reducing polyketide synthase with very unusual C-terminal hydrolase and methyltransferase domains. Expression of stpks1 in Aspergillus oryzae leads to the production of prestrobilurin A when the fermentation is supplemented with a benzoyl coenzyme A (CoA) analogue. This enables the discovery of a previously unobserved route to benzoyl CoA. Reconstruction of the gene cluster in A. oryzae leads to the formation of prestrobilurin A, and addition of the gene str9 encoding an FAD-dependent oxygenase leads to the key oxidative rearrangement responsible for the creation of the β-methoxyacrylate toxophore. Finally, two methyltransferases are required to complete the synthesis.

AB - Strobilurins from fungi are the inspiration for the creation of the β-methoxyacrylate class of agricultural fungicides. However, molecular details of the biosynthesis of strobilurins have remained cryptic. Here we report the sequence of genomes of two fungi that produce strobilurins and show that each contains a biosynthetic gene cluster, which encodes a highly reducing polyketide synthase with very unusual C-terminal hydrolase and methyltransferase domains. Expression of stpks1 in Aspergillus oryzae leads to the production of prestrobilurin A when the fermentation is supplemented with a benzoyl coenzyme A (CoA) analogue. This enables the discovery of a previously unobserved route to benzoyl CoA. Reconstruction of the gene cluster in A. oryzae leads to the formation of prestrobilurin A, and addition of the gene str9 encoding an FAD-dependent oxygenase leads to the key oxidative rearrangement responsible for the creation of the β-methoxyacrylate toxophore. Finally, two methyltransferases are required to complete the synthesis.

KW - Aspergillus oryzae

KW - Basidiomycota/enzymology

KW - Multigene Family

KW - Polyketide Synthases/metabolism

KW - Strobilurins/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85054104584&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-06202-4

DO - 10.1038/s41467-018-06202-4

M3 - Article

C2 - 30258052

AN - SCOPUS:85054104584

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3940

ER -