Publications

• A heterologous expression platform in Aspergillus nidulans for the elucidation of cryptic secondary metabolism biosynthetic gene clusters: discovery of the Aspergillus fumigatus sartorypyrone biosynthetic pathway.

  Lin S.Y., Oakley C.E., Jenkinson C.B., Chiang Y.M., Lee C.K., Jones C.G., Seidler P.M., Nelson H.M., Todd R.B., Wang C.C.C., Oakley B.R.

  <i>Aspergillus fumigatus</i> is a serious human pathogen causing life-threatening Aspergillosis in immunocompromised patients. Secondary metabolites (SMs) play an important role in pathogenesis, but the products of many SM biosynthetic gene clusters (BGCs) remain unknown. In this study, we have de ... >> More

  <i>Aspergillus fumigatus</i> is a serious human pathogen causing life-threatening Aspergillosis in immunocompromised patients. Secondary metabolites (SMs) play an important role in pathogenesis, but the products of many SM biosynthetic gene clusters (BGCs) remain unknown. In this study, we have developed a heterologous expression platform in <i>Aspergillus nidulans</i>, using a newly created genetic dereplication strain, to express a previously unknown BGC from <i>A. fumigatus</i> and determine its products. The BGC produces sartorypyrones, and we have named it the <i>spy</i> BGC. Analysis of targeted gene deletions by HRESIMS, NMR, and microcrystal electron diffraction (MicroED) enabled us to identify 12 products from the <i>spy</i> BGC. Seven of the compounds have not been isolated previously. We also individually expressed the polyketide synthase (PKS) gene <i>spyA</i> and demonstrated that it produces the polyketide triacetic acid lactone (TAL), a potentially important biorenewable platform chemical. Our data have allowed us to propose a biosynthetic pathway for sartorypyrones and related natural products. This work highlights the potential of using the <i>A. nidulans</i> heterologous expression platform to uncover cryptic BGCs from <i>A. fumigatus</i> and other species, despite the complexity of their secondary metabolomes. << Less

  Chem. Sci. 14:11022-11032(2023) [PubMed] [EuropePMC]

  This publication is cited by 6 other entries.

• A novel class of plant type III polyketide synthase involved in orsellinic acid biosynthesis from Rhododendron dauricum.

  Taura F., Iijima M., Yamanaka E., Takahashi H., Kenmoku H., Saeki H., Morimoto S., Asakawa Y., Kurosaki F., Morita H.

  <i>Rhododendron dauricum</i> L. produces daurichromenic acid, the anti-HIV meroterpenoid consisting of sesquiterpene and orsellinic acid (OSA) moieties. To characterize the enzyme responsible for OSA biosynthesis, a cDNA encoding a novel polyketide synthase (PKS), orcinol synthase (ORS), was clone ... >> More

  <i>Rhododendron dauricum</i> L. produces daurichromenic acid, the anti-HIV meroterpenoid consisting of sesquiterpene and orsellinic acid (OSA) moieties. To characterize the enzyme responsible for OSA biosynthesis, a cDNA encoding a novel polyketide synthase (PKS), orcinol synthase (ORS), was cloned from young leaves of <i>R. dauricum</i>. The primary structure of ORS shared relatively low identities to those of PKSs from other plants, and the active site of ORS had a unique amino acid composition. The bacterially expressed, recombinant ORS accepted acetyl-CoA as the preferable starter substrate, and produced orcinol as the major reaction product, along with four minor products including OSA. The ORS identified in this study is the first plant PKS that generates acetate-derived aromatic tetraketides, such as orcinol and OSA. Interestingly, OSA production was clearly enhanced in the presence of <i>Cannabis sativa</i> olivetolic acid cyclase, suggesting that the ORS is involved in OSA biosynthesis together with an unidentified cyclase in <i>R. dauricum</i>. << Less

  Front. Plant Sci. 7:1452-1452(2016) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.