Featured
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Exposure to environmental pollutants selects for xenobiotic-degrading functions in the human gut microbiome
In this study, the authors employ metagenomics to explore the impact of environmental pollution on the human gut microbiome using samples from a cohort living in a very polluted area in Southern Italy, showing that pollutants degradation genes are more abundant in subjects with higher blood levels of those specific xenobiotics.
- Francesca De Filippis
- , Vincenzo Valentino
- & Danilo Ercolini
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Article
| Open Access
Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies
Microbial heparin bioproduction is hampered by the difficulty of recombinant expression of active heparan sulfate N-deacetylase/N-sulfotransferase. Here, the authors solve the problem by developing a cellular system-based semisynthetic strategy and achieve the production of active heparin by engineered E. coli.
- Jian-Qun Deng
- , Yi Li
- & Ju-Zheng Sheng
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Article
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A modular and synthetic biosynthesis platform for de novo production of diverse halogenated tryptophan-derived molecules
De novo fermentation and synthetic pathway construction for halogen-containing molecules remain relatively underexplored. Here, the authors report a mix-and-match co-culture platform to de novo generate a large array of halogenated tryptophan derivatives in E. coli from glucose.
- Kevin B. Reed
- , Sierra M. Brooks
- & Hal S. Alper
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Article
| Open Access
Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members
Past intestinal distress is associated with diminished social behavior in mice. Here, the authors show that treatment with microbiota members that are enriched in neurotypical people versus people with ASD can ameliorate colitis severity and associated sociability deficits.
- D. Garrett Brown
- , Michaela Murphy
- & June L. Round
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Article
| Open Access
Synthetically-primed adaptation of Pseudomonas putida to a non-native substrate D-xylose
Pseudomonas putida is becoming a host of choice for the valorization of lignocellulosic substrates. Here, the authors provide insight into the adaptation of this bacterium to the non-native substrate D-xylose, enabled by metabolic engineering and adaptive laboratory evolution.
- Pavel Dvořák
- , Barbora Burýšková
- & Martin Benešík
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Accurate and rapid antibiotic susceptibility testing using a machine learning-assisted nanomotion technology platform
Sturm et. al developed a 2 to 4 h antibiotic susceptibility test based on bacterial vibrations. This diagnostic test applies to the most frequently found gram-negative bacteria in bloodstream infections and demonstrates its potential in contributing to faster treatment decisions.
- Alexander Sturm
- , Grzegorz Jóźwiak
- & Danuta Cichocka
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Article
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A citric acid cycle-deficient Escherichia coli as an efficient chassis for aerobic fermentations
While tricarboxylic acid cycle (TCA cycle) is required for heterotrophic microbes, it reduces carbon yield of industrial products due to the release of excess CO2. Here, the authors construct an E. coli strain without a functional TCA cycle and demonstrate its feasibility as a chassis strain for production of four separate compounds.
- Hang Zhou
- , Yiwen Zhang
- & Baixue Lin
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Article
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Increased CO2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast
CO2 fixation plays an important role to make bioproduction cost competitive. Here, the authors take 3-hydroxypropionic acid as an example to showcase how to achieve high carbon yield production through increasing the accessible bicarbonate, minimizing native CO2 release and avoiding carbon waste.
- Ning Qin
- , Lingyun Li
- & Zihe Liu
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Article
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Systems engineering of Escherichia coli for high-level glutarate production from glucose
Glutarate is a platform chemical widely used in the production of polyesters and polyamindes. Here, the authors design the shortest and thermodynamically favorable pathway, and increase glutarate production from glucose through systematic engineering of E. coli.
- Zhilan Zhang
- , Ruyin Chu
- & Cong Gao
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Article
| Open Access
Transgenic expression of cif genes from Wolbachia strain wAlbB recapitulates cytoplasmic incompatibility in Aedes aegypti
The Wolbachia cifA and cifB genes generate cytoplasmic incompatibility (CI) in insect hosts but the role of cifA is still debated. Here, the authors report the transgenic recapitulation of CI in the major arbovirus vector Aedes aegypti and provide evidence for cifA inhibiting cifB toxicity in the male germline.
- Cameron J. McNamara
- , Thomas H. Ant
- & Steven P. Sinkins
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Article
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Compositional and temporal division of labor modulates mixed sugar fermentation by an engineered yeast consortium
Synthetic microbial communities are suitable for mixed substrates fermentation and long metabolic pathway engineering. Here, the authors combine fermentation experiments with mathematical modeling to reveal the effect of compositional and temporal changes on division of labor in cellulosic ethanol production using two yeast strains.
- Jonghyeok Shin
- , Siqi Liao
- & Yong-Su Jin
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Article
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Rational strain design with minimal phenotype perturbation
No consensus exists on the computationally tractable use of dynamic models for strain design. To tackle this, the authors report a framework, nonlinear-dynamic-model-assisted rational metabolic engineering design, for efficiently designing robust, artificially engineered cellular organisms.
- Bharath Narayanan
- , Daniel Weilandt
- & Vassily Hatzimanikatis
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Article
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De novo biosynthesis of antiarrhythmic alkaloid ajmaline
Ajmaline is an antiarrhythmic monoterpenoid indole alkaloid produced by the root of Rauwolfia serpentina. Here, the authors complete the ajmaline biosynthetic pathway by identifying two reductases and two esterases, and achieve the de novo ajmaline biosynthesis by engineering Baker’s yeast.
- Jun Guo
- , Di Gao
- & Yang Qu
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Article
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Cross-feeding promotes heterogeneity within yeast cell populations
Cellular heterogeneity in cell populations of isogenic origin is driven by diverse factors such as nutrient availability and interactions with neighbouring cells. Here, Hu et al. study plasmid retention dynamics in yeast populations, and show that the exchange of complementary metabolites between plasmid-carrying prototrophs and plasmid-free auxotrophs allows the latter to proliferate in selective environments.
- Kevin K. Y. Hu
- , Ankita Suri
- & Victoria S. Haritos
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| Open Access
Optogenetic spatial patterning of cooperation in yeast populations
Microbial communities are the siege of complex metabolic interactions including cooperation and competition. Here, the authors report the utilization of optogenetics and spatial light-patterning to activate the expression of the invertase SUC2 at selected locations and selectively switch cooperation and competition roles of the yeast cells.
- Matthias Le Bec
- , Sylvain Pouzet
- & Pascal Hersen
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Microbial interactions shape cheese flavour formation
Cheese fermentation and flavour formation are the result of complex biochemical reactions driven by the activity of multiple microorganisms. Here, the authors identify microbial interactions as a mechanism underlying flavour formation in Cheddar cheese.
- Chrats Melkonian
- , Francisco Zorrilla
- & Ahmad A. Zeidan
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Article
| Open Access
Engineering a synthetic energy-efficient formaldehyde assimilation cycle in Escherichia coli
One-carbon substrates are attractive feedstocks for circular bioeconomy. Here, the authors design an erythrulose monophosphate (EuMP) cycle for formaldehyde assimilation, demonstrate the activity of the core reactions in E. coli, and show its integration with pathway reactions existed in pentose phosphate pathway and glycolysis.
- Tong Wu
- , Paul A. Gómez-Coronado
- & Hai He
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Article
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Reconfiguration of the reductive TCA cycle enables high-level succinic acid production by Yarrowia lipolytica
Redox imbalance limits succinic acid (SA) biosynthesis from glucose via the reductive tricarboxylic acid (TCA) cycle in yeast. Here, the authors engineering the aerobic yeast Yarrowia lipolytica for efficient SA production without pH control via coupling the oxidative and reductive TCA cycle for NADH regeneration in mitochondria.
- Zhiyong Cui
- , Yutao Zhong
- & Qingsheng Qi
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| Open Access
Engineering artificial photosynthesis based on rhodopsin for CO2 fixation
Microbial rhodopsins are major contributors to global light harvesting on Earth, but their role in carbon fixation is unclear. Here, the authors construct an artificial photosynthesis system by combining rhodopsin with an extracellular electron uptake mechanism for photoelectrosynthetic CO2 fixation in Ralstonia eutropha.
- Weiming Tu
- , Jiabao Xu
- & Wei E. Huang
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Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
It’s challenging to produce natural products using single strains of engineered microbes fed by renewable carbon sources. Here, the authors assemble a microbial consortium consisting of engineered S. stipitis and S. cerevisiae for streamlined production of (S)-norcoclaurine from glucose and xylose simultaneously.
- Meirong Gao
- , Yuxin Zhao
- & Zengyi Shao
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Article
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Discovery and remodeling of Vibrio natriegens as a microbial platform for efficient formic acid biorefinery
Formic acid (FA) is a promising CO2-equivalent feedstock for onecarbon biorefinery, but microbial host that can efficiently utilize FA is unavailable. Here, the authors engineer a non-native closed loop in Vibrio natriegens and demonstrate its application in promoting FA utilization.
- Jinzhong Tian
- , Wangshuying Deng
- & Yang Gu
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Article
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The oxygen-tolerant reductive glycine pathway assimilates methanol, formate and CO2 in the yeast Komagataella phaffii
One carbon compounds such as CO2, methanol and formate are cost-effective and environmentally friendly microbial feedstocks for biomanufacturing. Here, the authors report the oxygen tolerant reductive glycine pathway in Komagataella phaffii can co-assimilate CO2, methanol and formate.
- Bernd M. Mitic
- , Christina Troyer
- & Diethard Mattanovich
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Article
| Open Access
Regulation of species metabolism in synthetic community systems by environmental pH oscillations
Most synthetic communities are unidirectional or two-way interaction without dynamic feedback. Here, the authors report a dynamic feedback system involving artificial cell species, biological cell species, and their environment using pH-sensitive molecule that phase-shift between fluid and gel phases.
- Shubin Li
- , Yingming Zhao
- & Xiaojun Han
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Article
| Open Access
Diurnal switches in diazotrophic lifestyle increase nitrogen contribution to cereals
Engineering ammonium excretion diazotrophs suffers from severe penalties to the bacteria. Here, the authors utilize a thermo-sensitive glutamine synthetase-based regulatory switch that permits diurnal changes in diazotrophic lifestyle, coincident with seasonal temperatures for cereal cultivation.
- Yuqian Tang
- , Debin Qin
- & Yi-Ping Wang
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Article
| Open Access
Streptomyces alleviate abiotic stress in plant by producing pteridic acids
Soil microbiota can increase crop resilience to abiotic stressors. Here the authors show that Streptomyces produce bioactive spiroketal polyketides to enhance plant growth under drought and salt stress.
- Zhijie Yang
- , Yijun Qiao
- & Ling Ding
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Article
| Open Access
Engineering sulfonate group donor regeneration systems to boost biosynthesis of sulfated compounds
Sufficient supply of sulfonate group donor is critical to biomanufacturing of the sulfate containing compounds. Here, the authors engineer two sulfonate group donor regeneration systems, including 3'-phosphoadenosine-5'-phosphosulfate and the newly discovered 5'-phosphosulfate, to boost biosynthesis of sulfated compounds.
- Ruirui Xu
- , Weijao Zhang
- & Zhen Kang
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Perspective
| Open Access
The potential of CO2-based production cycles in biotechnology to fight the climate crisis
The utilization of one-carbon assimilation pathways for bioproduction represents a promising direction towards a more sustainable bio-based economy. Here, the authors compare the thermodynamic efficiencies and energy demand of C1-assimilation pathways and discuss their implementation for energy, material, and food production.
- Simone Bachleitner
- , Özge Ata
- & Diethard Mattanovich
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Article
| Open Access
Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways
Gut microbiota has been reported to influence osteoporosis risk, but the individual species, and underlying mechanisms, remain largely unknown. Here, the authors identify Bacteroides vulgatus and serum valeric acid as potential targets for osteoporosis prevention/treatment.
- Xu Lin
- , Hong-Mei Xiao
- & Hong-Wen Deng
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Perspective
| Open Access
Synergistic investigation of natural and synthetic C1-trophic microorganisms to foster a circular carbon economy
Using one carbon (C1) molecules as primary feedstock for bioproduction holds great potential for a circular and carbon neutral economy. Here, the authors discuss the potential of merging knowledge gained from natural and synthetic C1-trophic organisms to expedite the development of efficient C1-based biomanufacturing.
- Enrico Orsi
- , Pablo Ivan Nikel
- & Stefano Donati
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| Open Access
Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
Generating and controlling cell collective behavior is important for synthetic biology and bioproduction. Here, the authors show the diversification dynamic and the fitness cost associated with cell switching are coupled in yeast and bacteria, and demonstrate the feasibility of controlling diversification regimes.
- Lucas Henrion
- , Juan Andres Martinez
- & Frank Delvigne
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Article
| Open Access
Hydrodynamic tearing of bacteria on nanotips for sustainable water disinfection
Common methods for water disinfection involve oxidation or irradiation, and are often associated with a high carbon footprint and formation of toxic byproducts. Here, the authors describe a nano-structured material that is highly effective at killing bacteria in water through a hydrodynamic mechanism driven by mild water flow, in the absence of additional energy supply.
- Lu Peng
- , Haojie Zhu
- & Hong-Ying Hu
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Article
| Open Access
Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis
The inherent toxicity of the aromatic compounds to the chassis strain hampers further improvement of bioproduction. Here, the authors show that membrane rigidifying effect of resveratrol can be attenuated by exogenous supplementation of palmitelaidic acid or linoleic acid in fermentation of Corynebacterium glutamicum.
- Apilaasha Tharmasothirajan
- , Josef Melcr
- & Jan Marienhagen
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Article
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Screening non-conventional yeasts for acid tolerance and engineering Pichia occidentalis for production of muconic acid
Baker’s yeast is a workhorse of industrial biotechnology, but it is not suited to overproduce many bulk bioproducts, especially organic acids. Here, the authors identify Pichia occidentalis as an acid tolerant yeast and engineer it for the production of muconic acid using a newly developed genome editing toolkit.
- Michael E. Pyne
- , James A. Bagley
- & Vincent J. J. Martin
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Article
| Open Access
Protein engineering and iterative multimodule optimization for vitamin B6 production in Escherichia coli
Pyridoxine (PN), the most common commercial form of vitamin B6, has been chemically synthesized using expensive and toxic chemicals. Here, the authors employ parallel pathway engineering, protein engineering, and iterative multimodule optimization for high level PN production in E. coli.
- Linxia Liu
- , Jinlong Li
- & Dawei Zhang
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Article
| Open Access
Using a synthetic machinery to improve carbon yield with acetylphosphate as the core
In metabolic engineering, releasing of carbon in the form of CO2 leads to significant decrease of atomic economy. Here, the authors construct a carbon-conserving pathway, which converts glucose into acetyl phosphate without carbon loss, with oscillatory system to improve production of multiple target compounds.
- Likun Guo
- , Min Liu
- & Guang Zhao
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Article
| Open Access
A polycistronic system for multiplexed and precalibrated expression of multigene pathways in fungi
Unlike prokaryotic hosts, most genes in eukaryotes are transcribed to monocistronic mRNA for single protein translation. Here, the authors develop a polycistronic system for multiplexed and precalibrated expression of multiple genes, and show its application in constructing yeast cell factories for terpenoids production.
- Qun Yue
- , Jie Meng
- & Shuobo Shi
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Article
| Open Access
Cryo-EM and femtosecond spectroscopic studies provide mechanistic insight into the energy transfer in CpcL-phycobilisomes
CpcL-phycobilisome (PBS) is a type of small PBS that transfers energy directly to photosystem I (PSI) without a core structure. Here the authors combine cryo-electron microscopy and ultrafast spectroscopy to explore energy transfer pathway in CpcL-PBS.
- Lvqin Zheng
- , Zhengdong Zhang
- & Jindong Zhao
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Article
| Open Access
Unlocking the potentials of cyanobacterial photosynthesis for directly converting carbon dioxide into glucose
Photosynthetic glucose production is well controlled due to its complex interactions with other cellular processes. Here, the authors identify that the native glucokinase activity is the bottleneck restricting the metabolism potential for glucose synthesis and engineer a cyanobacterium strain that can produce 5 g/L of glucose.
- Shanshan Zhang
- , Jiahui Sun
- & Xuefeng Lu
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Article
| Open Access
Engineering a new-to-nature cascade for phosphate-dependent formate to formaldehyde conversion in vitro and in vivo
A key step in the assimilation of formate is its reduction into formaldehyde. Here, the authors develop a two-enzyme route in which formate is activated into formyl phosphate and reduced by NAD(P)H into formaldehyde and confirm its functionality in vitro and in vivo.
- Maren Nattermann
- , Sebastian Wenk
- & Tobias J. Erb
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Article
| Open Access
Roles of adenine methylation in the physiology of Lacticaseibacillus paracasei
The bacterium Lacticaseibacillus paracasei is used in the food industry and as a probiotic. Here, the authors use multi-omics and high-throughput chromosome conformation capture analyses to investigate the roles of a type of DNA methylation (N6-methyladenine modification) in this organism.
- Jie Zhao
- , Meng Zhang
- & Wenyi Zhang
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Article
| Open Access
Teasing out missing reactions in genome-scale metabolic networks through hypergraph learning
A computational method for rapid and accurate gap-filling of metabolic networks without using phenotypic data is unavailable. Here, the authors address this problem by developing a deep learning based method that can predict missing reactions using topological features of the metabolic networks.
- Can Chen
- , Chen Liao
- & Yang-Yu Liu
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Article
| Open Access
Targeted and high-throughput gene knockdown in diverse bacteria using synthetic sRNAs
Using synthetic sRNAs to knockdown target genes has been restricted to a limited number of bacteria. Here, the authors develop a broad-host-range synthetic sRNA platform and show its application in 16 bacterial species, including mitigating virulence-associated phenotypes in pathogens and production of chemicals via metabolic engineering.
- Jae Sung Cho
- , Dongsoo Yang
- & Sang Yup Lee
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Review Article
| Open Access
The microbial food revolution
In this Review article, the authors discuss the potential of microorganisms as a solution to the challenges faced by our food system. Engineered microorganisms can be used to produce enhanced foods and ingredients in a sustainable manner. The technical, economical, and societal limitations are also discussed together with the current and future perspectives.
- Alicia E. Graham
- & Rodrigo Ledesma-Amaro
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Perspective
| Open Access
A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast
Yeasts, Saccharomyces cerevisiae and Pichia pastoris, are promising chassis for the production of nature products (NPs). Here, the author discusses establishing a comprehensive platform for sustainable production of NPs via system-associated optimization at genetics, temporal controllers, productivity screening, and scalability levels.
- Gita Naseri
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Article
| Open Access
Construction of a synthetic metabolic pathway for biosynthesis of 2,4-dihydroxybutyric acid from ethylene glycol
Ethylene glycol is an attractive two-carbon alcohol substrate for bioproduction as it can be derived from CO2 or syngas. Here, the authors design a five-step synthetic metabolic pathway in E. coli to enable the carbon-conserving biosynthesis of the platform chemical 2,4-dihydroxybutyric acid from ethylene glycol.
- Cláudio J. R. Frazão
- , Nils Wagner
- & Thomas Walther
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Perspective
| Open Access
Toward sustainable space exploration: a roadmap for harnessing the power of microorganisms
Establishing sustainable approaches for human space exploration is key to achieve independency from terrestrial resources, as well as for ethical considerations. Here the authors highlight microbial biotechnologies that will support sustainable processes for space-based in situ resource utilization and loop-closure, and may be translatable to Earth applications.
- Rosa Santomartino
- , Nils J. H. Averesch
- & Luis Zea
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Article
| Open Access
Tandemly duplicated CYP82Ds catalyze 14-hydroxylation in triptolide biosynthesis and precursor production in Saccharomyces cerevisiae
Hydroxylation at the C-14 position of triptolide is critical for its potent antitumor activity. Here, the authors report two CYP82Ds catalyze the 14-hydroxylation reaction via metabolic grid and achieve heterologous bioproduction of triptolide precursor in engineered Saccharomyces cerevisiae.
- Yifeng Zhang
- , Jie Gao
- & Luqi Huang
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Article
| Open Access
The natural pyrazolotriazine pseudoiodinine from Pseudomonas mosselii 923 inhibits plant bacterial and fungal pathogens
Natural antimicrobial metabolites produced by soil microorganisms can be used as green pesticides. Here, the authors isolated a Pseudomonas mosselii strain 923 from rice rhizosphere soils and identify the compound pyrazolotriazine pseudoiodinine inhibits the growth of plant bacterial and fungal pathogens.
- Ruihuan Yang
- , Qing Shi
- & Gongyou Chen
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Article
| Open Access
A modular vaccine platform enabled by decoration of bacterial outer membrane vesicles with biotinylated antigens
Antigen display on outer membrane vesicles (OMVs) can be difficult to control and highly variable. Here, the authors describe a universal approach called AvidVax for linking biotinylated antigens to the exterior of OMVs and enabling rapid vaccine assembly.
- Kevin B. Weyant
- , Ayomide Oloyede
- & Matthew P. DeLisa
The link between ancient microbial fluoride resistance mechanisms and bioengineering organofluorine degradation or synthesis