The solanapyrone biosynthetic gene cluster was cloned from Alternaria solani. It consists of six genes-sol1-6-coding for a polyketide synthase, an O-methyltransferase, a dehydrogenase, a transcription factor, a flavin-dependent oxidase, and cytochrome P450. The prosolanapyrone synthase (PSS) encoded by sol1 was expressed in Aspergillus oryzae and its product was identified as desmethylprosolanapyrone I (8). Although PSS is closely related to the PKSs/Diels-Alderases LovB and MlcA of lovastatin and compactin biosynthesis, it did not catalyze cycloaddition. Sol5, encoding a flavin-dependent oxidase (solanapyrone synthase, SPS), was expressed in Pichia pastoris and purified. The purified recombinant SPS showed activity for the formation of (-)-solanapyrone A (1) from achiral prosolanapyrone II (2), establishing that this single enzyme catalyzes both the oxidation and the subsequent cycloaddition reaction, possibly as a Diels-Alder enzyme.

The crystal structure of SEp22, a DNA‐binding protein from starved cells from Salmonella enterica subsp. enterica serovar Enteritidis, has been determined in two forms: the native state at 1.25 Å resolution and an iron‐soaked form at 1.30 Å resolution. The SEp22 protomers form a dodecameric shell with 23 symmetry and a single iron ion per protomer was found at the ferroxidase centre in the iron‐soaked form. Along the threefold axes of the 23 symmetry, hydrophilic Asp channels that consist of Asp146 were found. Iron ions may flow into the cavity of the dodecameric shell through the Asp channels.

The inside cover picture shows solanapyrone A biosynthesis by a highly reducing iterative type I polyketide synthase, prosolanapyrone synthase (PSS), and a possible "Diels-Alderase", solanapyrone synthase (SPS). PSS (top) produces desmethylprosolanapyrone I. In the catalytic cavity of SPS (center), prosolanapyrone II is oxidized to solanapyrone A, possibly by exo-selective Diels-Alder cyclization. For more information, see the paper by I. Fujii et al. on p. 1245 ff. Inside CoverKen Kasahara , Takanori Miyamoto, Takashi Fujimoto, Hiroki Oguri, Tetsuo Tokiwano , Hideaki Oikawa, Yutaka Ebizuka, and Isao Fujii* The inside cover picture shows solanapyrone A biosynthesis by a highly reducing iterative type I polyketide synthase, prosolanapyrone synthase (PSS), and a possible "DielsAlderase", solanapyrone synthase (SPS). PSS (top) produces desmethylprosolanapyrone I. In the catalytic cavity of SPS (center), prosolanapyrone II is oxidized to solanapyrone A, possibly by exo-selective Diels-Alder cyclization. For more information, see the paper by I. Fujii et al. on p. 1245 ff.

Amplification of MYCN is observed in high-risk neuroblastomas (NBs) and is associated with a poor prognosis. MYCN expression is directly regulated by multiple transcription factors, including OCT4, MYCN, CTCF, and p53 in NB. Our previous study showed that inhibition of p53 binding at the MYCN locus induces NB cell death. However, it remains unclear whether other transcription factors contribute to NB cell survival. In this study, we revealed that the inhibition of OCT4 binding at the MYCN locus, a critical site for the human-specific OCT4-MYCN positive feedback loop, induces caspase-2-mediated cell death in MYCN-amplified NB. We used the CRISPR/deactivated Cas9 (dCas9) technology to specifically inhibit transcription factors from binding to the MYCN locus in the MYCN-amplified NB cell lines CHP134 and IMR32. In both cell lines, the inhibition of OCT4 binding at the MYCN locus reduced MYCN activity. Differentially downregulated transcripts were associated with high-open reading frame (ORF) dominance score, which is associated with the translation efficiency of transcripts. These transcripts were enriched in splicing factors, including MYCN-target genes such as HNRNPA1 and PTBP1. Furthermore, transcripts with high-ORF dominance were significantly associated with genes whose high expression is associated with a poor prognosis of NB. In conclusion, the inhibition of OCT4 binding at the MYCN locus resulted in reduced MYCN activity, which in turn led to the downregulation of high-ORF dominance transcripts and subsequently induced caspase-2-mediated cell death in MYCN-amplified NB cells. Therefore, disruption of the human-specific OCT4-MYCN positive feedback loop may serve as an effective therapeutic strategy for MYCN-amplified NB.