摘要：Modulating the extracellular matrix microenvironment is critical for achieving the desired macrophage phenotype in immune investigations or tumor *** de novo protein design and biosynthesis techniques,herein,we designed a biomimetic polypeptide self-assembled nano-immunomodulator to trigger the activation of a specific macrophage *** was intended to be made up of(GGSGGPGGGPASAAANSASRATSNSP)n,the RGD motif from collagen,and the IKVAV motif from *** combination of these domains allows the biomimetic polypeptide to assemble into extracellular matrix-like nanofibrils,creating an extracellular matrix-like milieu for ***,changing the concentration further provides a facile route to fine-tune macrophage polarization,which enhances antitumor immune responses by precisely resetting tumor-associated macrophage immune responses into an M1-like phenotype,which is generally considered to be tumor-killing macrophages,primarily antitumor,and *** metal or synthetic polymer-based nanoparticles,this polypeptide-based nanomaterial exhibits excellent biocompatibility,high efficacy,and precise tunability in immunomodulatory *** encouraging findings motivate us to continue our research into cancer immunotherapy applications in the future.

摘要：Vinblastine has been used clinically as one of the most potent therapeutics for the treatment of several types of ***,the traditional plant extraction method suffers from unreliable supply,low abundance,and extremely high ***,we use synthetic biology approach to engineer Saccharomyces cerevisiae for de novo biosynthesis of vindoline and catharanthine,which can be coupled chemically or biologically to *** the basis of a platform strain with sufficient supply of precursors and cofactors for biosynthesis,we reconstituted,debottlenecked,and optimized the biosynthetic pathways for the production of vindoline and *** vindoline biosynthetic pathway represents one of the most complicated pathways ever reconstituted in microbial cell *** shake flask fermentation,our engineered yeast strains were able to produce catharanthine and vindoline at a titer of 527.1 and 305.1μg·liter^(−1),respectively,without accumulating detectable amount of pathway *** study establishes a representative example for the production of valuable plant natural products in yeast.