Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin (1) and variecolactone (2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues (5-7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Constructing Spatially Separated Cage-Like Z-scheme Heterojunction Photocatalyst for Enhancing Photocatalytic H2 Evolution.

Heterojunctions coupled into micro-mesoscopic structures is an attractive strategy to optimize the light harvesting and carrier separation of semiconductor photocatalysts. A self-templating method of ion exchange is reported to synthesize an exquisite hollow cage-structured Ag2 S@CdS/ZnS that direct Z-scheme heterojunction photocatalyst. On the ultrathin shell of the cage, Ag2 S, CdS, and ZnS with Zn-vacancies (VZn ) are arranged sequentially from outside to inside. Among them, the photogenerated electrons are excited by ZnS to the VZn energy level and then recombine with the photogenerated holes that are generated by CdS, while the electrons remained in the CdS conduction band are further transferred to Ag2 S. The ingenious cooperation of the Z-scheme heterojunction with the hollow structure optimizes the photogenerated charges transport channel, spatially separated the oxidation and reduction half-reactions, decreases the charge recombination probability, and simultaneously improves the light harvesting efficiency. As a result, the photocatalytic hydrogen evolution activity of the optimal sample is 136.6 and 17.3 times higher than that of cage-like ZnS with VZn and CdS by, respectively. This unique strategy demonstrates the tremendous potential of the incorporation of heterojunction construction to morphology design of photocatalytic materials, and also provided a reasonable route for designing other efficient synergistic photocatalytic reactions.