Publications

• Biosynthesis of LL-Z1272beta: discovery of a new member of NRPS-like enzymes for aryl-aldehyde formation.

  Li C., Matsuda Y., Gao H., Hu D., Yao X.S., Abe I.

  LL-Z1272β (1) is a prenylated aryl-aldehyde produced by several fungi; it also serves as a key pathway intermediate for many fungal meroterpenoids. Despite its importance in the biosynthesis of natural products, the molecular basis for the biosynthesis of 1 has yet to be elucidated. Here we identi ... >> More

  LL-Z1272β (1) is a prenylated aryl-aldehyde produced by several fungi; it also serves as a key pathway intermediate for many fungal meroterpenoids. Despite its importance in the biosynthesis of natural products, the molecular basis for the biosynthesis of 1 has yet to be elucidated. Here we identified the biosynthetic gene cluster for 1 from Stachybotrys bisbyi PYH05-7, and elucidated the biosynthetic route to 1. The biosynthesis involves a polyketide synthase, a prenyltransferase, and a nonribosomal peptide synthetase (NRPS)-like enzyme, which is responsible for the generation of the aldehyde functionality. Interestingly, the NRPS-like enzyme only accepts the farnesylated substrate to catalyze the carboxylate reduction; this represents a new example of a substrate for adenylation domains. << Less

  ChemBioChem 17:904-907(2016) [PubMed] [EuropePMC]

  This publication is cited by 2 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.

• Complete biosynthetic pathways of ascofuranone and ascochlorin in Acremonium egyptiacum.

  Araki Y., Awakawa T., Matsuzaki M., Cho R., Matsuda Y., Hoshino S., Shinohara Y., Yamamoto M., Kido Y., Inaoka D.K., Nagamune K., Ito K., Abe I., Kita K.

  Ascofuranone (AF) and ascochlorin (AC) are meroterpenoids produced by various filamentous fungi, including <i>Acremonium egyptiacum</i> (synonym: <i>Acremonium sclerotigenum</i>), and exhibit diverse physiological activities. In particular, AF is a promising drug candidate against African trypanos ... >> More

  Ascofuranone (AF) and ascochlorin (AC) are meroterpenoids produced by various filamentous fungi, including <i>Acremonium egyptiacum</i> (synonym: <i>Acremonium sclerotigenum</i>), and exhibit diverse physiological activities. In particular, AF is a promising drug candidate against African trypanosomiasis and a potential anticancer lead compound. These compounds are supposedly biosynthesized through farnesylation of orsellinic acid, but the details have not been established. In this study, we present all of the reactions and responsible genes for AF and AC biosyntheses in <i>A. egyptiacum</i>, identified by heterologous expression, in vitro reconstruction, and gene deletion experiments with the aid of a genome-wide differential expression analysis. Both pathways share the common precursor, ilicicolin A epoxide, which is processed by the membrane-bound terpene cyclase (TPC) AscF in AC biosynthesis. AF biosynthesis branches from the precursor by hydroxylation at C-16 by the P450 monooxygenase AscH, followed by cyclization by a membrane-bound TPC AscI. All genes required for AC biosynthesis (<i>ascABCDEFG</i>) and a transcriptional factor (<i>ascR</i>) form a functional gene cluster, whereas those involved in the late steps of AF biosynthesis (<i>ascHIJ</i>) are present in another distantly located cluster. AF is therefore a rare example of fungal secondary metabolites requiring multilocus biosynthetic clusters, which are likely to be controlled by the single regulator, AscR. Finally, we achieved the selective production of AF in <i>A. egyptiacum</i> by genetically blocking the AC biosynthetic pathway; further manipulation of the strain will lead to the cost-effective mass production required for the clinical use of AF. << Less

  Proc. Natl. Acad. Sci. U.S.A. 116:8269-8274(2019) [PubMed] [EuropePMC]

  This publication is cited by 9 other entries.