Project description:The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi.
Project description:Three new butenolides aspernolides H-J (<b>1</b>-<b>3</b>) together with seven known ones (<b>4</b>-<b>10</b>) were isolated from the fungus <i>Aspergillus</i> sp. CBS-P-2. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopic data, HR-ESI-MS analysis, and their absolute configuration were determined by circular dichroism (CD) analysis. All the compounds were evaluated for the antioxidant effects by DPPH and ABTS methods, the antitumor activities against four human tumor cell lines (HL-60, ASPC1, HCT-116 and PC-3) and antimicrobial activities. Compounds <b>4</b>-<b>10</b> showed significant activity against DPPH (IC<sub>50</sub> = 15.9-34.3 ?M) and compounds <b>1</b>-<b>10</b> exhibited significant ABTS free radical scavenging activity (IC<sub>50</sub> = 2.8-33.1 ?M). Compounds <b>2</b>, <b>5</b> and <b>11</b> showed potent cytotoxic activities against HL-60 cell lines with IC<sub>50</sub> values of 39.4, 13.2 and 16.3 ?M, respectively. Compound <b>10</b> showed good antimicrobial activity against <i>Staphylococcus aureus</i> with minimum inhibitory concentration (MIC) of 21.3 ?M.