Application of an Efficient Gene Targeting System Linking Secondary Metabolites to their Biosynthetic Genes in <i>Aspergillus terreus</i>

Guo, Chun-Jun; Knox, Benjamin P.; Sanchez, James F.; Chiang, Yi‐Ming; Bruno, Kenneth S.; Wang, Clay C. C.

doi:10.1021/ol401384v

Cited by 52 publications

(69 citation statements)

References 20 publications

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“…AstPT encoded by ATEG_09980 functions as a prenyltransferase of methylated asterriquinone and catalyzes both reverse N1-and regular C2-prenylation (Tarcz et al 2014). Gene deletion experiments suggested the involvement of ATEG_02823 and ATEG_00702 in the biosynthesis of butyrolactones and asterriquinone CT5, respectively (Guo et al 2013). However, no biochemical data are available for the encoded enzymes.…”

Section: Resultsmentioning

confidence: 99%

C7-prenylation of tryptophanyl and O-prenylation of tyrosyl residues in dipeptides by an Aspergillus terreus prenyltransferase

Wunsch

Zou

Linne

et al. 2014

Appl Microbiol Biotechnol

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During our search for novel prenyltransferases, a putative gene ATEG_04218 from Aspergillus terreus raised our attention and was therefore amplified from strain DSM 1958 and expressed in Escherichia coli. Biochemical investigations with the purified recombinant protein and different aromatic substrates in the presence of dimethylallyl diphosphate revealed the acceptance of all the tested tryptophan-containing cyclic dipeptides. Structure elucidation of the main enzyme products by NMR and MS analyses confirmed the attachment of the prenyl moiety to C-7 of the indole ring, proving the identification of a cyclic dipeptide C7-prenyltransferase (CdpC7PT). For some substrates, reversely C3- or N1-prenylated derivatives were identified as minor products. In comparison to the known tryptophan-containing cyclic dipeptide C7-prenyltransferase CTrpPT from Aspergillus oryzae, CdpC7PT showed a much higher substrate flexibility. It also accepted cyclo-L-Tyr-L-Tyr as substrate and catalyzed an O-prenylation at the tyrosyl residue, providing the first example from the dimethylallyltryptophan synthase (DMATS) superfamily with an O-prenyltransferase activity towards dipeptides. Furthermore, products with both C7-prenyl at tryptophanyl and O-prenyl at tyrosyl residue were detected in the reaction mixture of cyclo-L-Trp-L-Tyr. Determination of the kinetic parameters proved that (S)-benzodiazepinedione consisting of a tryptophanyl and an anthranilyl moiety was accepted as the best substrate with a K M value of 204.1 μM and a turnover number of 0.125 s(-1). Cyclo-L-Tyr-L-Tyr was accepted with a K M value of 1,411.3 μM and a turnover number of 0.012 s(-1).

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Section: Resultsmentioning

confidence: 99%

C7-prenylation of tryptophanyl and O-prenylation of tyrosyl residues in dipeptides by an Aspergillus terreus prenyltransferase

Wunsch

Zou

Linne

et al. 2014

Appl Microbiol Biotechnol

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“…In contrast, a non-ribosomal peptide synthetase (NRPS)-like enzyme MelA was revealed to synthesise an uncommon aspulvinone E-derived Asp-melanin together with a tyrosinase TyrP [17,18], indicating the production to be of DOPA-type. Nevertheless, the pigmentation pathways of A. terreus are still mysterious, being only partially discovered.…”

Section: Introductionmentioning

confidence: 99%

Melanisation of Aspergillus terreus—Is Butyrolactone I Involved in the Regulation of Both DOPA and DHN Types of Pigments in Submerged Culture?

et al. 2017

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Pigments and melanins of fungal spores have been investigated for decades, revealing important roles in the survival of the fungus in hostile environments. The key genes and the encoded enzymes for pigment and melanin biosynthesis have recently been found in Ascomycota, including Aspergillus spp. In Aspergillus terreus, the pigmentation has remained mysterious with only one class of melanin biogenesis being found. In this study, we examined an intriguing, partially annotated gene cluster of A. terreus strain NIH2624, utilizing previously sequenced transcriptome and improved gene expression data of strain MUCL 38669, under the influence of a suggested quorum sensing inducing metabolite, butyrolactone I. The core polyketide synthase (PKS) gene of the cluster was predicted to be significantly longer on the basis of the obtained transcriptional data, and the surrounding cluster was positively regulated by butyrolactone I at the late growth phase of submerged culture, presumably during sporulation. Phylogenetic analysis of the extended PKS revealed remarkable similarity with a group of known pigments of Fusarium spp., indicating a similar function for this PKS. We present a hypothesis of this PKS cluster to biosynthesise a 1,8-dihydroxynaphthalene (DHN)-type of pigment during sporulation with the influence of butyrolactone I under submerged culture.

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“…Since we have established the genetic linkage between apvA and aspulvinones, 7 we set out to identify the first tailoring enzyme, which we presumed was responsible for prenylating 1 to give 2 (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

et al. 2015

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Application of an Efficient Gene Targeting System Linking Secondary Metabolites to their Biosynthetic Genes in Aspergillus terreus

Cited by 52 publications

References 20 publications

C7-prenylation of tryptophanyl and O-prenylation of tyrosyl residues in dipeptides by an Aspergillus terreus prenyltransferase

C7-prenylation of tryptophanyl and O-prenylation of tyrosyl residues in dipeptides by an Aspergillus terreus prenyltransferase

Melanisation of Aspergillus terreus—Is Butyrolactone I Involved in the Regulation of Both DOPA and DHN Types of Pigments in Submerged Culture?

Spatial regulation of a common precursor from two distinct genes generates metabolite diversity

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