Heavy metal pollution is a global knotty problem and fungi hold promising potential for the remediation of wastewater containing heavy metals. Here, a new highly chromium-tolerance species, Penicillium janthinellum P1, is investigated. The genome of P1 was sequenced and assembled into 30 Mb genome size containing 10,955 predicted protein-coding genes with a GC content of 46.16% through an integrated method of Illumina short-read sequencing and single-molecule real-time Pacific Biosciences sequencing platforms. Through a phylogenetic analysis with model species of fungi, the evolutionary divergence time of Penicillium janthinellum P1 and Penicillium oxalicum 114-2 was estimated to be 74 MYA. 33 secondary metabolism gene clusters were identified via antiSMASH software, mainly including non-ribosomal peptide synthase genes and T1 polyketide synthase genes. 525 genes were annotated to encode enzymes that act on carbohydrates, involving 101 glucose-degrading enzymes and 24 polysaccharide synthase. By whole-genome sequence analysis, large numbers of metal resistance genes were found in strain P1. Especially ABC transporter and Superoxide dismutase ensure that the P1 fungus can survive in a chromium-polluted environment. ChrA and ChrR were also identified as key genes for chromium resistance. Analysis of their genetic loci revealed that the specific coding-gene arrangement may account for the fungus’s chromium resistance. Genetic information and comparative analysis of Penicillium janthinellum are valuable for further understanding the mechanism of high resistance to heavy metal chromium, and gene loci analysis provides a new perspective for identifying chromium-resistant strains.

Residual disease is the major cause for colorectal cancer (CRC) relapse. Herein, we explore whether and how a natural molecule CADPE killed heterogenic populations in a panel of CRC cell lines with KRAS/BRAF mutations that are natively resistant to EGFR- or VEGFR-targeted therapy, without sparing persistent cells, a reservoir of the disease relapse. Results showed that CADPE killed the tumor bulk and residual cells in the panel of CRC cell lines, rapidly inactivated c-Myc, STAT3, and NF-κB, and then decreased the protein levels of key signaling molecules for CRC, such as β-catenin, Notch1, and the nodes of mTOR pathways; eukaryotic translation initiation factors (eIF4F); anti-apoptotic proteins (Bcl-xl, Mcl-1, and survivin); and stemness-supporting molecules (CD133, Bim-1, and VEGF). In terms of mechanism of action, concurrent downregulation of Mcl-1, Bcl-xl, and survivin was necessary for CADPE to kill CRC bulk cells, while additional depletion of CD133 and VEGF proteins was required for killing the residual CRC cells. Moreover, the disabled c-Myc, STAT3, NF-κB, and eIF4F were associated with the broadly decreased levels of anti-apoptosis proteins and pro-stemness proteins. Consistently, CADPE suppressed CRC tumor growth associated with robust apoptosis and depleted levels of c-Myc, STAT3, NF-κB, eIF4F, anti-apoptotic proteins, and pro-stemness proteins. Our findings showed the promise of CADPE for treating CRC and suggested a rational polytherapy that disables c-Myc, STAT3, NF-κB, and eIF4F for killing CRC residual disease.