Molecular and Chemical Characterization of the Biosynthesis of the 6-MSA-Derived Meroterpenoid Yanuthone D in Aspergillus niger.

SummarySecondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanI, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA

A novel method of comparing laser trim pattern geometries of thin film resistors

We present the results from stable isotope labeled precursor feeding studies combined with ultrahigh performance liquid chromatography-high resolution mass spectrometry for the identification of labeled polyketide (PK) end-products. Feeding experiments were performed with ¹³C₈-6-methylsalicylic acid (6-MSA) and ¹³C₁₄-YWA1, both produced in-house, as well as commercial ¹³C₇-benzoic acid and ²H₇-cinnamic acid, in species of <i>Fusarium, Byssochlamys, Aspergillus</i>, and <i>Penicillium</i>. Incorporation of 6-MSA into terreic acid or patulin was not observed in any of six evaluated species covering three genera, because the 6-MSA was shunted into (2<i>Z</i>,4<i>E</i>)-2-methyl-2,4-hexadienedioic acid. This indicates that patulin and terreic acid may be produced in a closed compartment of the cell and that (2<i>Z</i>,4<i>E</i>)-2-methyl-2,4-hexadienedioic acid is a detoxification product toward terreic acid and patulin. In <i>Fusarium</i> spp., YWA1 was shown to be incorporated into aurofusarin, rubrofusarin, and antibiotic Y. In <i>A. niger</i>, benzoic acid was shown to be incorporated into asperrubrol. Incorporation levels of 0.7–20% into the end-products were detected in wild-type strains. Thus, stable isotope labeling is a promising technique for investigation of polyketide biosynthesis and possible compartmentalization of toxic metabolites