Featured
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Article
| Open AccessManipulation of sterol homeostasis for the production of 24-epi-ergosterol in industrial yeast
Brassinolide (BL) is one of the most active compounds among phytohormone brassinosteroids (BRs) and can be used for plant growth and development regulation. Here, the authors report the construction of an artificial pathway in baker’s yeast for scalable production of 24-epi-ergosterol, a precursor for BL semi-synthesis.
- Yiqi Jiang
- , Zhijiao Sun
- & Lirong Yang
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Article
| Open AccessBioprinting microporous functional living materials from protein-based core-shell microgels
Extrusion bioprinting can be used to produce living materials but controlling cell microenvironments is challenging. Here, the authors use a type of core-shell microgel ink that decouples cell culture from material processing to produce functional materials with a range of potential applications.
- Yangteng Ou
- , Shixiang Cao
- & Tuomas P. J. Knowles
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Article
| Open AccessOrthogonal glycolytic pathway enables directed evolution of noncanonical cofactor oxidase
Engineering enzymes to accept noncanonical cofactor biomimetics is difficult. Here, the authors establish a self-sufficient growth selection method and demonstrate its application in engineering the Lactobacillus pentosus NADH oxidase to efficiently recycle reduced nicotinamide mononucleotide (NMNH).
- Edward King
- , Sarah Maxel
- & Han Li
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Article
| Open AccessBiodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin
High-crystallinity poly(ethylene terephthalate) is a major recycling challenge. Here, the authors show an engineered whole-cell biocatalyst showing adhesive hydrophobin and PETase on the surface of cells, for biodegradation of PET.
- Zhuozhi Chen
- , Rongdi Duan
- & Zefang Wang
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Article
| Open AccessDisulfiram ameliorates nonalcoholic steatohepatitis by modulating the gut microbiota and bile acid metabolism
Nonalcoholic steatohepatitis (NASH) has been linked with the gut-liver axis. Here, the authors show that disulfiram (DSF) reduces Clostridium-mediated 7α-dehydroxylation activity to suppress secondary bile acid biosynthesis and ameliorate NASH in mice, and validate DSF regulation of the gut-liver axis in healthy men in a self-controlled clinical trial.
- Yuanyuan Lei
- , Li Tang
- & Bo Tang
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Article
| Open AccessGut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia
Here, the authors show that SARS-CoV-2 infection causes gut microbiome dysbiosis and gut epithelial cell alterations in a mouse model, and correlate dysbiosis observed in COVID-19 patients with blood stream infections, matching reads of bacterial sequences from stool samples to organisms found in the blood.
- Lucie Bernard-Raichon
- , Mericien Venzon
- & Jonas Schluter
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Article
| Open AccessA fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin
Biosynthesis of the flavonoid naringenin in plants and bacteria is commonly catalysed by a type III polyketide synthase (PKS) using one p-coumaroyl-CoA and three malonyl-CoA molecules as substrates. Here, the authors report a fungal non-ribosomal peptide synthetase PKS hybrid FnsA catalysing the formation of naringenin.
- Hongjiao Zhang
- , Zixin Li
- & Wen-Bing Yin
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Perspective
| Open AccessHarnessing bioengineered microbes as a versatile platform for space nutrition
Long-duration human space travel creates challenges for maintaining healthy diets. Here the authors discuss using synthetic biology approaches to modify yeast into an optimal, and enjoyable, food production platform.
- Briardo Llorente
- , Thomas C. Williams
- & Ian T. Paulsen
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Article
| Open AccessA miniaturized bionic ocean-battery mimicking the structure of marine microbial ecosystems
Marine ecosystems are dominated by microbial communities. Inspired by the photoelectric conversion feature of the marine ecosystems, the authors design a four-species microbial community to mimic primary producer, primary degrader, and ultimate consumers, and show its ability to convert light into electricity for over one month.
- Huawei Zhu
- , Liru Xu
- & Yin Li
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Article
| Open AccessMetabolic pathway assembly using docking domains from type I cis-AT polyketide synthases
Assembly artificial pathway in design connecting media can increase biosynthetic efficiency, but the choice of connecting media is limited. Here, the authors develop a new protein assembly strategy using a pool of docking peptides from polyketide synthase and show its application in astaxanthin biosynthesis in E. coli.
- Xixi Sun
- , Yujie Yuan
- & Tian Ma
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Article
| Open AccessBiosynthesis of plant hemostatic dencichine in Escherichia coli
Biosynthetic pathway of dencichine, a plant derived nature product that has found various pharmacological applications, is still elusive. Here, the authors design artificial pathways through retro-biosynthesis approaches and achieve its efficient production in E. coli by systematic metabolic and enzymatic engineering.
- Wenna Li
- , Zhao Zhou
- & Qipeng Yuan
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Article
| Open AccessBatch effects removal for microbiome data via conditional quantile regression
Here, the authors present ConQuR, a conditional quantile regression method that removes microbiome batch effects through non-parametric modeling of complex microbial read counts, while preserving the signals of interest.
- Wodan Ling
- , Jiuyao Lu
- & Michael C. Wu
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Article
| Open AccessKinetic compartmentalization by unnatural reaction for itaconate production
Unlike eukaryotic system, bacterial hosts lack membranous system, which is one of the limitations for efficient metabolic engineering. Here, the authors report a kinetic compartmentalization strategy to increase substrate availability from competitive reactions for the efficient production of itaconate in E. coli.
- Dae-yeol Ye
- , Myung Hyun Noh
- & Gyoo Yeol Jung
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Article
| Open AccessPolyvinyl chloride degradation by a bacterium isolated from the gut of insect larvae
Microbial degradation of polyvinyl chloride (PVC) has previously been reported, but little is known about the degrading strains and enzymes. Here, Zhe et al. isolate a PVC-degrading bacterium from the gut of insect larvae and shed light on the PVC degradation pathway using a multi-omic approach.
- Zhe Zhang
- , Haoran Peng
- & Feng Ju
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Article
| Open AccessGeneration of an Escherichia coli strain growing on methanol via the ribulose monophosphate cycle
Using one carbon compounds as feedstock is a promising approach in abating climate change. Here, the authors report the conversion of E. coli into a synthetic methylotroph that assimilates methanol via the ribulose monophosphate cycle and a set of distinctive mutations.
- Philipp Keller
- , Michael A. Reiter
- & Julia A. Vorholt
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Article
| Open AccessMultiplexed mobilization and expression of biosynthetic gene clusters
Efficient mobilization and expression of biosynthetic gene clusters (BGCs) into heterologous hosts is needed for microbial natural products discovery. Here, the authors improve the CONKAT-seq strategy by simultaneously capturing the BCGs into a single large insert library and demonstrate its ability to discover natural products with new structures and potent antibacterial activity.
- Vincent Libis
- , Logan W. MacIntyre
- & Sean F. Brady
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Article
| Open AccessExpanding the terpene biosynthetic code with non-canonical 16 carbon atom building blocks
Establishing methods to access the chemical space that lies beyond canonical terpenoid biosynthesis will increase the applications of isoprenoids. Here, the authors reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones by engineered yeast and synthesize 28 different unique terpenes.
- Codruta Ignea
- , Morten H. Raadam
- & Sotirios C. Kampranis
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Article
| Open AccessStructural bases for aspartate recognition and polymerization efficiency of cyanobacterial cyanophycin synthetase
CphA1 catalyzes the synthesis of cyanophycin polypeptide consisting of equimolar amounts of aspartate and arginine as a fixed nitrogen reservoir in cyanobacteria. Here, the authors solve the cryo-EM structures of CphA1, revealing the aspartate binding mode and protein dynamics required for cyanophycin elongation.
- Takuya Miyakawa
- , Jian Yang
- & Masaru Tanokura
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Article
| Open AccessDirected evolution of phosphite dehydrogenase to cycle noncanonical redox cofactors via universal growth selection platform
Engineering enzymes to utilize the noncanonical redox cofactors such as nicotinamide mononucleotide (NMN + ) is challenging. Here, the authors report a growth-based selection platform for NMN + -reducing enzyme engineering and show its application in developing a phosphite dehydrogenase with improved catalytic efficiency.
- Linyue Zhang
- , Edward King
- & Han Li
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Article
| Open AccessMuconic acid production from glucose and xylose in Pseudomonas putida via evolution and metabolic engineering
Muconic acid is a platform chemical with wide industrial applicability. Here, the authors report efficient muconate production from glucose and xylose by engineered Pseudomonas putida strain using adaptive laboratory evolution, metabolic modeling, and rational strain engineering strategies.
- Chen Ling
- , George L. Peabody
- & Gregg T. Beckham
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Article
| Open AccessMolecular characterization of the missing electron pathways for butanol synthesis in Clostridium acetobutylicum
Ferredoxin-NAD(P) + oxidoreductases are important enzymes for redox balancing in n-butanol production by Clostridium acetobutylicum, but the encoding genes remain unknown. Here, the authors identify the long sought-after genes and increase n-butanol production by optimizing the levels of the two enzymes.
- Céline Foulquier
- , Antoine Rivière
- & Isabelle Meynial-Salles
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Article
| Open AccessSystematic strategies for developing phage resistant Escherichia coli strains
Phage contamination is a persistent problem in industrial biotechnology processes employing bacterial strains. Here, the authors report the construction of E. coli host strains with broad antiphase activities via the genomic integration of the Ssp defense system and mutations of components essential for phage infection cycles.
- Xuan Zou
- , Xiaohong Xiao
- & Sang Yup Lee
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Article
| Open AccessMetaproteomics reveals enzymatic strategies deployed by anaerobic microbiomes to maintain lignocellulose deconstruction at high solids
Efficient solubilization of plant cell wall carbohydrates is required for microbial production of biofuels from lignocellulosic biomass. Here, the authors employ metaproteomics to interrogate enzymatic strategies of a methanogenic microbiome deconstructing switchgrass at increasing solids loading.
- Payal Chirania
- , Evert K. Holwerda
- & Lee R. Lynd
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Article
| Open AccessVertex protein PduN tunes encapsulated pathway performance by dictating bacterial metabolosome morphology
Morphology of metabolosomes affects the encapsulated pathway performance. Here, the authors combine experimental characterizations with structural and kinetic modeling to reveal how the shell protein PduN changes the morphology of 1,2-propanediol utilization (Pdu) metabolosome and how this morphology shift impacts Pdu function.
- Carolyn E. Mills
- , Curt Waltmann
- & Danielle Tullman-Ercek
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Article
| Open AccessChain flexibility of medicinal lipids determines their selective partitioning into lipid droplets
Lipid droplet (LD) is a highly dynamic organelle capable of regulating lipid metabolism, storage and transportation. Here, by combining molecular dynamics simulations and microbial LD engineering, the authors demonstrate that the structural flexibility of lipids is one of decisive factors in selective partitioning into LDs.
- So-Hee Son
- , Gyuri Park
- & Ju Young Lee
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Article
| Open AccessOrder-of-magnitude enhancement in photocurrent generation of Synechocystis sp. PCC 6803 by outer membrane deprivation
The low extracellular electron transfer activity hampers the application of cyanobacteria in biophotovoltaics. Here, the authors report an order-of-magnitude enhancement in photocurrent generation of the cyanobacterium by deprivation of the outer cell membrane.
- Shoko Kusama
- , Seiji Kojima
- & Shuji Nakanishi
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Article
| Open AccessImproving recombinant protein production by yeast through genome-scale modeling using proteome constraints
Due to the complexity of the protein secretory pathway, strategy suitable for the production of a certain recombination protein cannot be generalized. Here, the authors construct a proteome-constrained genome-scale protein secretory model for yeast and show its application in the production of different misfolded or recombinant proteins.
- Feiran Li
- , Yu Chen
- & Jens Nielsen
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Article
| Open AccessAn in vivo gene amplification system for high level expression in Saccharomyces cerevisiae
Gene dosage-based expression upregulation suffers from instability and random gene integration. Here, the authors report HapAmp, a method that uses haploinsufficiency as evolutionary force to drive in vivo gene amplification, and demonstrate its applications in protein and biochemical production in yeast.
- Bingyin Peng
- , Lygie Esquirol
- & Claudia E. Vickers
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Article
| Open AccessUnlocking the functional potential of polyploid yeasts
Domesticated industrial yeast strains are sterile, which hampers to breed strains with novel properties. Here, the authors employ the genetics paradigm return-to-growth to induce genome wide recombination in two sterile polyploid industrial yeasts and identify clones with superior biotechnological traits.
- Simone Mozzachiodi
- , Kristoffer Krogerus
- & Gianni Liti
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Article
| Open AccessRationally engineering santalene synthase to readjust the component ratio of sandalwood oil
Controlling the component ratios of plant essential oils is challenging in their heterologous bioproduction. Here, the authors combine metabolic and enzymatic engineering strategies to achieve the production of sandalwood oil with a desirable component ratio in baker’s yeast.
- Wenlong Zha
- , Fan Zhang
- & Jiachen Zi
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Article
| Open AccessMetabolic preference assay for rapid diagnosis of bloodstream infections
It is currently slow to identify bloodstream infection pathogens. Here the authors report a rapid metabolic preference assay that uses the pattern of metabolic fluxes observed in ex-vivo microbial cultures to identify common pathogens and determine their antimicrobial susceptibility profiles.
- Thomas Rydzak
- , Ryan A. Groves
- & Ian A. Lewis
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Article
| Open AccessRedesigning regulatory components of quorum-sensing system for diverse metabolic control
Existing quorum sensing (QS) circuits are less sophisticated for regulating multiple sets of genes or operons. Here, the authors redesign the luxR-luxI intergenic sequence of the lux-type QS system and apply it to achieve diverse metabolic control in salicylic acid and 4-hydroxycoumarin biosynthesis in E. coli.
- Chang Ge
- , Zheng Yu
- & Qipeng Yuan
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Article
| Open AccessEnhancing biofuels production by engineering the actin cytoskeleton in Saccharomyces cerevisiae
Product toxicity is one of the factors that hinder biofuel production. Here, the authors engineer the actin cytoskeleton to increase cell growth and production of n-butanol and medium-chain fatty acids in Saccharomyces cerevisiae.
- Hui Liu
- , Pei Zhou
- & Liming Liu
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Article
| Open AccessHarnessing phosphonate antibiotics argolaphos biosynthesis enables a synthetic biology-based green synthesis of glyphosate
Current commercialized production processes of glyphosate are generally associated with manufacturing hazards and toxic wastes. Here, to address the problems, the authors report the bioproduction of aminomethylphosphonate (AMP) and a chemical process for the conversion of AMP to glyphosate.
- Leixia Chu
- , Xiaoxia Luo
- & Jiangtao Gao
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Article
| Open AccessMetabolic engineering strategies to produce medium-chain oleochemicals via acyl-ACP:CoA transacylase activity
Microbial production of oleochemicals involves strategies of expressing thioesterase to narrow the substrate pool for the termination enzyme at the expense of one ATP. Here, the authors developed an alternative energy-efficient strategy to use of an acyl-ACP transacylase to produce medium chain oleochemicals in E. coli.
- Qiang Yan
- , William T. Cordell
- & Brian F. Pfleger
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Article
| Open AccessBiosynthesizing structurally diverse diols via a general route combining oxidative and reductive formations of OH-groups
Diols are important bulk and fine chemicals, but bioproduciton of branch-chain diols is hampered by the unknown biological route. Here, the authors report the expanding of amino acid metabolism for biosynthesis of branch-chain diols via a general route of combined oxidative and reductive formations of hydroxyl groups.
- Yongfei Liu
- , Wei Wang
- & An-Ping Zeng
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Article
| Open AccessDesign of stable and self-regulated microbial consortia for chemical synthesis
Stability and tunability are two desirable properties of microbial consortia-based bioproduction. Here, the authors integrate a caffeate-responsive biosensor into two and three strains coculture system to achieve autonomous regulation of strain ratios for coniferol and silybin/isosiltbin production, respectively.
- Xianglai Li
- , Zhao Zhou
- & Qipeng Yuan
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Article
| Open AccessCRISPR-assisted rational flux-tuning and arrayed CRISPRi screening of an l-proline exporter for l-proline hyperproduction
Corynebacterium glutamicum is a major workhorse in industrial biomanufacturing of amino acids. Here, the authors employ CRISPR-assisted rational flux-tuning and CRISPRi screening of a L-proline exporter to covert a wild-type C. glutamicum to a hyperproducer of L-proline.
- Jiao Liu
- , Moshi Liu
- & Jibin Sun
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Article
| Open AccessWhole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies
Metabolically active organelles compete for cytosolic space and resources during metabolism rewiring. Here, the authors develop a computational model of yeast metabolism and resource allocation to predict condition- and compartment-specific proteome constraints that govern metabolic strategies.
- Ibrahim E. Elsemman
- , Angelica Rodriguez Prado
- & Bas Teusink
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Article
| Open AccessRemoval of lycopene substrate inhibition enables high carotenoid productivity in Yarrowia lipolytica
Substrate inhibition has not been widely studied in the context of synthetic biology and metabolic engineering. Here, the authors report removal of lycopene substrate inhibition by two different strategies and enable high carotenoid productivity in Yarrowia lipolytica.
- Yongshuo Ma
- , Nian Liu
- & Gregory Stephanopoulos
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Article
| Open AccessMachine learning-informed and synthetic biology-enabled semi-continuous algal cultivation to unleash renewable fuel productivity
Growth limitation caused by mutual shading and the high harvest cost hamper algal biofuel production. Here, the authors overcome these two problems by designing a semi-continuous algal cultivation system and an aggregation-based sedimentation strategy to achieve high levels production of biomass and limonene.
- Bin Long
- , Bart Fischer
- & Joshua S. Yuan
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Article
| Open AccessEngineering the stambomycin modular polyketide synthase yields 37-membered mini-stambomycins
Genetic engineering of the type I polyketide synthases (PKSs) to produce desirable analogous remains largely inefficient. Here, the authors leverage multiple approaches to delete seven internal modules from the stambomycin PKS and generate 37-membered mini-stambomycin macrolactones.
- Li Su
- , Laurence Hôtel
- & Kira J. Weissman
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Article
| Open AccessEngineering Bacillus subtilis for the formation of a durable living biocomposite material
Despite the advances in engineered living materials (ELMs), the diversity of ELMs especially those that are capable of autonomous self-fabrication and regeneration, is low. Here, the authors engineer a resilient ELM biocomposite using Bacillus subtilis and secreted EutM proteins as selfassembling scaffold building blocks.
- Sun-Young Kang
- , Anaya Pokhrel
- & Claudia Schmidt-Dannert
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Article
| Open AccessReprogramming microbial populations using a programmed lysis system to improve chemical production
Microbial ecosystem-based bioproduction requires the regulation of phenotypic structure of microbial populations. Here, the authors report the construction of a programmed lysis system and its ability for reprograming microbial cooperation in poly(lactate-co-3-hydroxybutyrate) and butyrate production by E. coli strains.
- Wenwen Diao
- , Liang Guo
- & Liming Liu
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Article
| Open AccessGeneration of a Gluconobacter oxydans knockout collection for improved extraction of rare earth elements
Bioleaching of rare earth elements using microorganisms offers an environmentally friendly alternative to thermochemical extraction. Here, Schmitz et al. generate a whole-genome knockout collection of mutants for one such microorganism, Gluconobacter oxydans, and identify genes affecting the production of acidic biolixiviant and thus bioleaching efficacy.
- Alexa M. Schmitz
- , Brooke Pian
- & Buz Barstow
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Article
| Open AccessEfficient biosynthesis of nucleoside cytokinin angustmycin A containing an unusual sugar system
Angustmycin A is a nucleoside antibiotic having anti-mycobacterial and cytokinin activities. Here, the authors report the whole pathway leading to angustmycin A biosynthesis in Streptomyces and achieve the heterologous production of angustmycin A in E. coli.
- Le Yu
- , Wenting Zhou
- & Wenqing Chen
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Article
| Open AccessAptamer-assisted tumor localization of bacteria for enhanced biotherapy
Bacteria-based therapy has shown promise for cancer treatment. To enhance tumor accumulation, here the authors describe the design of tumor specific aptamer-conjugated bacteria, to improve intratumor localization and enhance therapeutic efficacy.
- Zhongmin Geng
- , Zhenping Cao
- & Weihong Tan
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Article
| Open AccessDesigning the bioproduction of Martian rocket propellant via a biotechnology-enabled in situ resource utilization strategy
Returning from Mars to Earth requires propellant. The authors propose a biotechnology-enabled in situ resource utilization (bioISRU) process to produce a Mars specific rocket propellant, 2,3-butanediol, using cyanobacteria and engineered E. coli, with lower payload mass and energy usage compared to chemical ISRU strategies.
- Nicholas S. Kruyer
- , Matthew J. Realff
- & Pamela Peralta-Yahya
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Article
| Open AccessIntracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases
The limited ability of cancer therapeutics in crossing the cancer cell membrane hampers their therapeutic potential. Here, the authors report Salmonella-based system for intracellular delivery of protein drugs, e.g. caspase-3, and show reduction of tumors in mouse models of breast and liver cancer.
- Vishnu Raman
- , Nele Van Dessel
- & Neil S. Forbes