Scientists made progress in the insights into the structure and function of EfpA: a lipid transporter in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) efflux pump EfpA has been implicated in resistance to multiple drugs. Its critical role in cell viability highlights it as a promising anti-TB drug target. In this study, scientists solved the cryo-EM structures of EfpA in complex with lipids and inhibitor BRD-8000.3, respectively. For the first time, they elucidated that EfpA functions a lipid transporter. Their research results will accelerate the development of antibiotics targeting EfpA.

Researchers Establish SpRY-Mediated Screens for Single-Base Resolution Dissection of Non-Coding Sequences and Unveil PAMless SpRY Target Search Kinetics

Scientists identify a de novo RBD-8 antibody rescuing the immune-evaded antibody against SARS-CoV-2 variants or sarbecoviruses

All EUA therapeutic mAbs against SARS-CoV-2 have been suspended because of the neutralization evasion. Therefore, the development of a class of mAbs that recognize a conserved cryptic epitope may avoid the adverse effects of escape mutations. Here, scientists identified two RBD-8 mAbs that recognize a cryptically conserved epitope among sarbecoviruses. These mAbs can broadly neutralize all sarbecoviruses and SARS-CoV-2 variants. Moreover, an RBD-8 can rescue the immune-evaded mAb to neutralize BQ.1 and BQ1.1 variants by engineering them as a bispecific antibody.

Scientists Quantify Proportion of Each Regulation Factor Contributing to Flux Changes in Saccharomyces Cerevisiae

A research team led by Prof. XIA Jianye from the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, quantified firstly each regulatory factor (protein abundance, thermodynamic potential, substrate concentration, allosteric effector concentration, and protein phosphorylation) contributing to reaction flux changes in central carbon metabolism of Saccharomyces cerevisiae cultured under aerobic respiration or aerobic fermentation conditions.

Reseachers engineer the hydrogen transfer pathway of an alcohol dehydrogenase to increase activity by rational enzyme design

The SUN Zhoutong group from Tianjin Institute of Industrial Biology, Chinese Academy of Sciences explored the crosslink between HT and enzyme activity by using an alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) as a model enzyme in the asymmetric reduction of a bulky prochiral ketone (4-chlorophenyl)(pyridin-2-yl)-methanone (CPMK).

Researchers construct the enhanced GBE variants for wider application

Glycosylase base editor (GBE) which converts C to G has been constructed. However, the editing efficiency and targeting scope remains to be further exploited. The GBE was optimized by fusing with transactivation modules, SunTag system or SpRY-Cas9, which led to an increase in editing efficiency and extended targeting scope. The construction of GBE variants with superior performance and versatile editing scope broadens the toolbox of base editors and contributes to genetic therapy with C-to-G mutation.

Carboxylic acid reductases enable intramolecular lactamization reactions

Researchers construct an operator-based expression toolkit for Bacillus subtilis for protein expression and biosynthetic pathway enginnering

An inducible-ON/OFF regulatory system using malO operator as a key element was developed in this study. The sequence, position, numbers and spacing distance of malO operators was identified and modulated, generating a series of activating or repressive promoters with tunable strength. A maximal induction factor of 790-fold was achieved in our system, and nine proteins from different organisms were expressed with high yields. This system can be utilized as gene switch, promoter enhancer or metabolic valve in synthetic biology applications.

Researchers make progress in amine dehydrogenase modification

SUN Zhoutong group from Tianjin Institute of Industrial Biology, Chinese Academy of Sciences, improved the activity of the engineered amine dehydrogenase (SpAmDH), a double–site (K68S/N261L) combinatorial leucine dehydrogenase derived from Sporosarcina psychrophila.

Reseachers unraveled the mechanism of enantio-controlling switches of an alcohol dehydrogenase

the SUN Zhoutong group from Tianjin Institute of Industrial Biology, Chinese Academy of Sciences address this question by using the Zn-dependent alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) as a model enzyme in the asymmetric reduction of a difficult-to-reduce ketone.