TY - JOUR

T1 - Oryzines A & B, Maleidride Congeners from Aspergillus oryzae and Their Putative Biosynthesis

AU - Wasil, Zahida

AU - Kuhnert, Eric

AU - Simpson, Thomas J.

AU - Cox, Russell J.

N1 - Funding information: This research was funded by EPSRC (Engineering and Physical Sciences research council) grant number EP/F066104/1 and DFG (Deutsche Forschungsgemeinschaft) grant number CO 1328/4-1. The authors thank Jenny Rose and Walid Bakeer for technical assistance. Zahida Wasil Thanks the Government of Pakistan (Higher Education Commission) for funding. We are grateful to Daniel Wibberg for the re-annotation of the A. oryzae genomic data.

PY - 2018/9

Y1 - 2018/9

N2 - Aspergillus oryzae is traditionally used in East Asia for the production of food and brewing. In addition, it has been developed into a suitable host for the heterologous expression of natural product biosynthetic genes and gene clusters, enabling the functional analysis of the encoded enzymes. A. oryzae shares a 99.5% genome homology with Aspergillus flavus, but their secondary metabolomes differ significantly and various compounds unique to A. oryzae have been reported. While using A. oryzae as a host for heterologous expression experiments we discovered two new metabolites in extracts of A. oryzae M-2-3 with an unusual maleidride backbone, which were named oryzine A and B. Their structures were elucidated by high resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analysis. Their structural relationships with known maleidrides implied involvement of a citrate synthase (CS) and a polyketide (PKS) or fatty acid synthase (FAS) in their biosynthesis. Analysis of the A. oryzae genome revealed a single putative biosynthetic gene cluster (BGC) consistent with the hypothetical biosynthesis of the oryzines. These findings increase knowledge of the chemical potential of A. oryzae and are the first attempt to link a novel product of this fungus with genomic data.

AB - Aspergillus oryzae is traditionally used in East Asia for the production of food and brewing. In addition, it has been developed into a suitable host for the heterologous expression of natural product biosynthetic genes and gene clusters, enabling the functional analysis of the encoded enzymes. A. oryzae shares a 99.5% genome homology with Aspergillus flavus, but their secondary metabolomes differ significantly and various compounds unique to A. oryzae have been reported. While using A. oryzae as a host for heterologous expression experiments we discovered two new metabolites in extracts of A. oryzae M-2-3 with an unusual maleidride backbone, which were named oryzine A and B. Their structures were elucidated by high resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analysis. Their structural relationships with known maleidrides implied involvement of a citrate synthase (CS) and a polyketide (PKS) or fatty acid synthase (FAS) in their biosynthesis. Analysis of the A. oryzae genome revealed a single putative biosynthetic gene cluster (BGC) consistent with the hypothetical biosynthesis of the oryzines. These findings increase knowledge of the chemical potential of A. oryzae and are the first attempt to link a novel product of this fungus with genomic data.

KW - Biosynthetic gene cluster

KW - Citrate synthase

KW - Fatty acid synthase

KW - Natural products

KW - Structure elucidation

UR - http://www.scopus.com/inward/record.url?scp=85054697972&partnerID=8YFLogxK

U2 - 10.3390/jof4030096

DO - 10.3390/jof4030096

M3 - Article

AN - SCOPUS:85054697972

VL - 4

JO - Journal of Fungi

JF - Journal of Fungi

IS - 3

M1 - 96

ER -