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A study examines the effects of mutations that occur naturally in T cell cancers, reporting that such mutations can potentially be exploited to increase the potency of T cell therapies.

Transforming model heterotrophs into autotrophs is usually accomplished by engineering one carbon assimilation pathway and/or employing laboratory evolution. Here, the authors report the engineering of cyanobacterial endosymbionts in yeasts to achieve photosynthetic growth, carbon assimilation and natural products production.

Cyanobacterial bioenergetics may have driven chloroplast evolution. Here, the authors show that cyanobacterial endosymbionts expressing plastidic ADP/ATP carrier translocases from red algae and glaucophyte support photosynthesis-driven bioenergetic endosymbiosis, but not those from green land plants.

Triacetic acid lactone (TAL) is a platform chemical with a wide range of applications. Here, the authors report the discovery of a polyketoacyl-CoA thiolase from Burkholderia sp. RF2-non_BP3, termed as BktBbr, which has unusually high in vivo and in vitro activity for production of TAL.

The endosymbiotic theory posits that chloroplasts in eukaryotes arise from bacterial endosymbionts. Here, the authors engineer the yeast/cyanobacteria chimeras and show that the engineered cyanobacteria perform chloroplast-like functions to support the growth of yeast cells under photosynthetic conditions.

Enhancer-driven genomic recording of transcriptional activity in multiplex (ENGRAM) is used for multiplex recording of the cell-type-specific activities of dozens to hundreds of cis-regulatory elements with high fidelity, sensitivity and reproducibility.

Agrobacterium-mediated transformation of plants and fungi is enhanced by plasmid copy number variants.

A DNA memory device, DNA Typewriter, uses sequential prime editing to record the order of multiple cellular events.

The oncogene MYC plays a key role in cancer initiation and progression. Using thousands of CRISPR perturbations, the authors investigate regulators of MYC in six different cancers. These tumor-specific regulators suggest potential therapeutic targets for this oncogene.

Medium- and branched-chain diols and amino alcohols are important industrial feedstocks, but they are biosynthetically challenging to produce. Here the authors introduce a modular polyketide synthase platform for the efficient production of these compounds.

Methyl jasmonate triggers saponin production in Saponaria vaccaria. Using transcriptome data and heterologous expression, the authors identify P450s and glycosyltransferases that modify triterpenoids. They also discover the pathway for UDP-D-fucose biosynthesis.

Systematic base-editing and computational screens identify specific cysteine residues on VPS35 in the retromer complex as key sensors that decrease mitochondrial translation in response to reactive oxygen species signals.

Bacteria have evolved proteinaceous microcompartments (BMCs) to control the passage of metabolites and facilitate catabolism in a micro-environment. Here, Yang et al. apply fluorescence microscopy to characterize the protein-protein interaction and assembly involved in the de novo biogenesis of propanediol-utilization (Pdu) metabolosomes and show that Pdu BMCs undergo a combination of ‘Shell first’ and ‘Cargo first’ assembly.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

The α-diazoester azaserine can be produced by Streptomyces albus engineered with a biosynthetic gene cluster and act as the carbene precursor for coupling with intracellularly produced styrene to generate unnatural amino acids containing a cyclopropyl group.

Engineering polyketide synthases can be challenging due to the absence of efficient high-throughput methods. Here, the authors used a solubility biosensor to identify stable variants from libraries of modified polyketide synthases.

This study provides a structural and functional characterisation of the phage resistance system, BREX. Went et. al. provide structures of the methyltransferase component, PglX, and rationally mutate PglX to retarget BREX defence against new phages.

Random barcoded transposon sequencing screens of generalist and typhoidal Salmonella determine the fitness effects of genes in a range of stress conditions and during macrophage infection, characterizing unknown genes and identifying typhoidal-specific vulnerabilities.

Single-cell quantitative expression reporters enable high-sensitivity quantitative characterization of cis-regulatory elements at the single-cell level in multicellular systems.

Fungi have the potential to produce sustainable foods for a growing population, but current products are based on a small number of strains with inherent limitations. Here, the authors develop genetic tools for an edible fungus and engineer its nutritional value and sensory appeal for alternative meat applications.

Engineered polyketide synthases (PKSs) have great potential as biocatalysts for the synthesis of chemically challenging molecules. Here the authors show a retrobiosynthesis approach to design and construct PKSs to produce a series of valerolactams for biopolymer production.

Malonyl-CoA (M-CoA) is essential for polyketide biosynthesis, but its limited availability constrains production. Here the authors engineer and evolve an orthogonal M-CoA pathway in Escherichia coli to improve M-CoA metabolism, increasing M-CoA levels and polyketide yields.

The authors develop a metabolic engineering strategy for improving polyketide production of industrial interest and discovering new natural products in bacteria.

CRISPR-based single-cell pooled screens that use linked barcodes suffer from lost sensitivity due to lentiviral template switching. The barcode-free CROP-seq design circumvents this problem.

Lignin conversion to higher value products is essential to the economic viability of lignocellulosic biorefineries. Here, the authors demonstrate the bioconversion of alkali pretreated lignin to itaconic acid by dynamic two stage fermentation using a signal-amplified nitrogen-limitation biosensor.

Complex RNA three-dimensional structures undergo functionally important programmed conformational changes. Here, the authors report how two structurally and functionally coupled RNA domains within a viral 3′-UTR sense the ribosome through conformational changes and respond by modulating translation.

Regulation of gene expression is a facet of human brain specialization. Here, the authors show that human-like expression of the CLOCK gene in the mouse neocortex enhances cognitive flexibility and neural connectivity, suggesting an evolutionary gain of function that may have contributed to human cognitive specialization.

QS-21—an FDA-approved vaccine adjuvant—and several structural analogues of QS-21 can be synthesized in engineered yeast strains, and this process is much less laborious compared with the conventional mode of extraction from the Chilean soapbark tree.

Combination of TCR or CAR T cells expressing the engineered CD47 variant 47_E with anti-CD47 antibody therapy results in synergistic antitumour efficacy due to T cell resistance to clearance by macrophages, while maintaining macrophage recruitment into the tumour microenvironment.

The authors describe a mechanism for the clearance of macromolecules from cerebrospinal fluid in which macromolecules traverse from periarterial to perivenous spaces, at sites where intersecting leptomeningeal perivascular (arteriovenous) spaces overlap.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The linker for activation of T cells (LAT) protein is involved in the activation of T cells. Here the authors discover micron scale LAT condensation events downstream of singly bound T-cell receptors during T cell activation and characterise how LAT condensation timing affects downstream T cell signalling.

Saccharomyces cerevisiae can be engineered to slowly use methanol; however, a co-carbon source is usually required to support its growth. Now, a Saccharomyces cerevisiae strain that can use methanol as the sole carbon source for growth, and produce value-added bioproducts, is developed.

Engineered biosensing bacteria can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. Here the authors present a robust biocontainment assisted by Cas9 and an engineered gene expression control combined in a genetically engineered human commensal bacterium that successfully functioned in a mouse intestinal tract as well as cell culture condition.

Production of aromatic monoterpene molecules in hop flowers is affected by genetic, environmental, and processing factors. Here, the authors engineer brewer’s yeast for the production of linalool and geraniol, and show pilot-scale beer produced by engineered strains reconstitutes some qualities of hop flavor.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The chemical synthesis of jasmonates is typically low yielding and can be laborious, whereas their extraction can be costly or environmentally hazardous. Now a de novo biosynthesis of jasmonic acid and its derivatives, methyl jasmonate and jasmonoyl isoleucine, is reported, using an engineered baker’s yeast.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Transcriptional profiling of 61,052 cells undergoing epithelial-to-mesenchymal transition (EMT) shows continuous waves of gene regulation, not discrete stages. A CRISPR screen orders EMT regulators along EMT progression.

Hydroxyglutarate synthase (HglS) converts 2-oxoadipate to D-2- hydroxyglutarate during lysine catabolism in bacteria. Here the authors use structural and biochemical approaches to show that HglS acts via successive decarboxylation and intramolecular hydroxylation and that homologous enzymes catalyze the final step of lysine catabolism in plants.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

The function of RNA-binding domain abundant in Apicomplexans (RAP) protein family members is largely unknown. Here, using high-throughput functional genomics, including metabolomics, Hollin et al. characterize two RAP proteins that are essential for Plasmodium falciparum survival and control mitochondrial rRNAs.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.