A new era of precise liquid regulation:Quasi-liquid

Common in nature and artificial systems,quasi-liquid represents a special phase under specific conditions,where precise regulations can be conducted to accommodate various applications,such as material,biology,life and manufacture.

Chemical–biological approaches for the direct regulation of cell–cell aggregation

Cell–cell aggregation is one of the most well-known modes of intercellular communication.The aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of organisms.In the past decades,cell–cell aggregation-related bioprocesses and molecular mechanisms have attracted enormous interest from scientists in biology,and bioengineering.People have developed a series of strategies to artificially regulate cell–cell aggregation through chemical–biological approaches.To date,not only the chemical reagents such as coordination compounds and polymers but also the biomacromolecules such as proteins and nucleic acids,are employed as the“cell glue”to achieve the control of the cell aggregation.So it is meaningful to review the recent advances of the chemical–biological approaches in cell–cell aggregation manipulation.In this review,we discuss the mechanisms and features of recently developed strategies to control cell–cell aggregation.We introduce molecules and designs relying on chemical reactions and biological conjugations respectively,and talk about their advantages and suitable applications.A perspective on the challenges in future applications in cell manipulation and cell-based therapy is also proposed.We expect this review could inspire innovative work on manipulating cell–cell aggregation and further modulate cell–cell interactions in the research of bio/chemical fields.

Promoter engineering enables precise metabolic regulation towards efficientβ-elemene production in Ogataea polymorpha

Precisely controlling gene expression is beneficial for optimizing biosynthetic pathways for improving the production.However,promoters in nonconventional yeasts such as Ogataea polymorpha are always limited,which results in incompatible gene modulation.Here,we expanded the promoter library in O.polymorpha based on transcriptional data,among which 13 constitutive promoters had the strengths ranging from 0–55%of PGAP,the commonly used strong constitutive promoter,and 2 were growth phase-dependent promoters.Subsequently,2 hybrid growth phase-dependent promoters were constructed and characterized,which had 2-fold higher activities.Finally,promoter engineering was applied to precisely regulate cellular metabolism for efficient production ofβ-elemene.The glyceraldehyde-3-phosphate dehydrogenase gene GAP was downregulated to drive more flux into pentose phosphate pathway(PPP)and then to enhance the supply of acetyl-CoA by using phosphoketolase-phosphotransacetylase(PK-PTA)pathway.Coupled with the phase-dependent expression of synthase module(ERG20∼LsLTC2 fusion),the highest titer of 5.24 g/L with a yield of 0.037 g/(g glucose)was achieved in strain YY150U under fed-batch fermentation in shake flasks.This work characterized and engineered a series of promoters,that can be used to fine-tune genes for constructing efficient yeast cell factories.

Remarkable enhancement of bleomycin production through precise amplification of its biosynthetic gene cluster in Streptomyces verticillus

Amplification of biosynthetic gene clusters is important to increase secondary metabolite production.However,the copy number of amplified gene clusters is difficult to control precisely.In this study,the tandem amplification of a 70 kb bleomycin biosynthetic gene cluster was precisely regulated through the combined strategy of a Zou A-dependent DNA amplification system and double-reporter-guided recombinant selection in Streptomyces verticillus ATCC15003.The production of bleomycin in the recombinant strain containing six copies of the bleomycin gene cluster was 9.59-fold higher than that in the wild-type strain.The combined strategy used in this study is powerful and applicable for precisely regulating the amplification of gene clusters and improving the corresponding secondary metabolite production.