Featured
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Perspective
| Open Access
Bio-integrated carbon capture and utilization: at the interface between capture chemistry and archaeal CO2 reduction
Existing carbon capture and utilization technologies are hindered by significant energy penalties. Here, the authors discuss the Bio-Integrated Carbon Capture and Utilization (BICCU) technology, which mitigates the energy penalties while generating valuable C1 and C2 products.
- Mads Ujarak Sieborg
- , Amalie Kirstine Hessellund Nielsen
- & Michael Vedel Wegener Kofoed
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Article
| Open Access
Phenotypic heterogeneity follows a growth-viability tradeoff in response to amino acid identity
Microbes frequently encounter suboptimal conditions. Here, Shabestary et al. show that phenotypic heterogeneity is an important feature of Saccharomyces species adaptation where amino acid identity serves as an environmental cue driving this adaptive process.
- Kiyan Shabestary
- , Cinzia Klemm
- & Rodrigo Ledesma-Amaro
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Article
| Open Access
Redirecting electron flow in Acetobacterium woodii enables growth on CO and improves growth on formate
Many acetogens, including Acetobacterium woodii, cannot grow on carbon monoxide and thus cannot be used as platform to detoxify industrial waste gas streams. Here, the authors solve the problem by knocking out the two [FeFe] hydrogenases HydA2 and HydBA in A. woodii.
- Jimyung Moon
- , Anja Poehlein
- & Volker Müller
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Article
| Open Access
MiDAS 5: Global diversity of bacteria and archaea in anaerobic digesters
Anaerobic digesters play an important role in biodegradation. In the MiDAS 5 project, the authors use global 16S rRNA sequencing to expand the microbial reference database, improving taxonomic classification and revealing how environmental factors and geography shape microbial communities in anaerobic digesters.
- Morten Kam Dahl Dueholm
- , Kasper Skytte Andersen
- & Per Halkjær Nielsen
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Article
| Open Access
Strain dynamics of contaminating bacteria modulate the yield of ethanol biorefineries
Industrial bioethanol production is driven by ecological interactions within the microbial community rather than the interactions within yeast population. Here, the authors identify bacteria affecting ethanol production and reveal temperature as the major driving force for strain-level dynamics.
- Felipe Senne de Oliveira Lino
- , Shilpa Garg
- & Morten Otto Alexander Sommer
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Article
| Open Access
Intein-mediated temperature control for complete biosynthesis of sanguinarine and its halogenated derivatives in yeast
Sanguinarine is a plant-derived benzylisoquinoline alkaloid that exhibits diverse pharmacological activities. Here, the authors report the complete biosynthesis of sanguinarine and halogenated derivatives using engineered yeast strains through a temperature-responsive dynamic control strategy.
- Yuanwei Gou
- , Dongfang Li
- & Jiazhang Lian
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Perspective
| Open Access
Bottlenecks in biobased approaches to plastic degradation
The way we generate and treat plastic waste is a key consideration in the transition from a take-make-waste model to a truly circular economy. Here, authors discuss their views on how biotechnology could contribute to solving the plastic problem, and the barriers we need to overcome to make such approaches a reality.
- Amelia R. Bergeson
- , Ashli J. Silvera
- & Hal S. Alper
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Perspective
| Open Access
The link between ancient microbial fluoride resistance mechanisms and bioengineering organofluorine degradation or synthesis
Microbial degradation and biosynthesis of fluorinated compounds is a field of increasing importance, but is hampered by the significant toxicity of fluoride. Here authors discuss emerging ideas on microbial defluorination/fluorination and fluoride resistance mechanisms, providing guidance on how this knowledge can guide future bioengineering approaches.
- Randy B. Stockbridge
- & Lawrence P. Wackett
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Article
| Open Access
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
| Open Access
Edible mycelium bioengineered for enhanced nutritional value and sensory appeal using a modular synthetic biology toolkit
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.
- Vayu Maini Rekdal
- , Casper R. B. van der Luijt
- & Jay D. Keasling
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Article
| Open Access
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
| Open Access
Combinatorial optimization of gene expression through recombinase-mediated promoter and terminator shuffling in yeast
Fine-tuning the expression of biosynthetic pathway genes is crucial to improve microbial production titres. Here, the authors present GEMbLeR, an optimization strategy to balance the expression of multiple genes simultaneously over a wide range.
- Charlotte Cautereels
- , Jolien Smets
- & Kevin J. Verstrepen
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Article
| Open Access
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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Article
| Open Access
ANCA: artificial nucleic acid circuit with argonaute protein for one-step isothermal detection of antibiotic-resistant bacteria
Antibiotic-resistant bacteria pose a growing threat to global health. Here, the authors present an artificial nucleic acid circuit with argonaute protein (ANCA) for one-step, amplification-free, and isothermal detection of carbapenemase-producing Klebsiella pneumoniae.
- Hyowon Jang
- , Jayeon Song
- & Taejoon Kang
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Article
| Open Access
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
| Open Access
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
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
Redox signaling-driven modulation of microbial biosynthesis and biocatalysis
Microbial communication has significant implications for industrial applications, but constructing communication systems which support coordinated behaviors is challenging. Here, the authors report an electron transfer triggered redox communication network and demonstrate its ability to coordinate microbial metabolism.
- Na Chen
- , Na Du
- & Quan Yuan
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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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Article
| Open Access
Structure of the transcription open complex of distinct σI factors
Here the authors show that σI factors encompass a unique, hitherto-unknown recognition mode of bacterial transcriptional promoters and represent a new distinctive class of σ70-family σ factors for bacterial transcription.
- Jie Li
- , Haonan Zhang
- & Ping Zhu
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Article
| Open Access
A thermostable type I-B CRISPR-Cas system for orthogonal and multiplexed genetic engineering
Thermophilic genetic manipulation tools are limited. Here the authors report a thermophilic type I-B CRISPR-Cas system and show it displays efficient transcriptional repression or DNA cleavage activity: they develop a tool for genome editing and transcriptional repression in both thermophile and mesophile hosts.
- Zhiheng Yang
- , Zilong Li
- & Weishan Wang
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Article
| Open Access
An end-to-end pipeline for succinic acid production at an industrially relevant scale using Issatchenkia orientalis
Microbial production of succinic acid at an industrially relevant scale has been hindered by high downstream processing costs arising from neutral pH fermentation. Here, the authors report an end-to-end pipeline for succinic acid production at low pH using engineered acid-tolerant Issatchenkia orientalis strain.
- Vinh G. Tran
- , Somesh Mishra
- & Huimin Zhao
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Article
| 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
Genome-resolved correlation mapping links microbial community structure to metabolic interactions driving methane production from wastewater
Anaerobic digestion of municipal mixed sludge is a microbial-mediated process that produces renewable natural gases such as methane. Here, Kieft et al. present the results of a two-year study of microbial community structure and function at a wastewater treatment plant, shedding light on metabolic interactions between microorganisms in relation with methane production.
- Brandon Kieft
- , Niko Finke
- & Steven J. Hallam
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Article
| Open Access
Enhancing photosynthetic CO2 fixation by assembling metal-organic frameworks on Chlorella pyrenoidosa
Concentrating CO2 around Rubisco is critical to improve photosynthetic efficiency for biomass yield. Here, the authors report the self-assembly of metal-organic frameworks (MOFs) on the surface of green alga Chlorella pyrenoidosa to enhance the photosynthetic carbon fixation.
- Dingyi Li
- , Hong Dong
- & Can Li
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Article
| Open Access
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
Phenotypically complex living materials containing engineered cyanobacteria
Engineered living materials (ELMs) are emerging as a field at the intersection of materials science and synthetic biology. Here, the authors describe a photosynthetic ELM composed of genetically engineered cyanobacteria in a hydrogel matrix, capable of bioremediation and inducible cell death.
- Debika Datta
- , Elliot L. Weiss
- & Jonathan K. Pokorski
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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
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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Article
| Open Access
Bi-terminal fusion of intrinsically-disordered mussel foot protein fragments boosts mechanical strength for protein fibers
High-yield production of well-performing protein materials is challenging due to their high molecular weights and repetitive sequences. Here the authors develop a method to boost the strength of low molecular-weight protein materials by bi-terminal fusion of intrinsically-disordered mussel foot protein fragments, while achieving high yield.
- Jingyao Li
- , Bojing Jiang
- & Fuzhong Zhang
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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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Article
| Open Access
Algal cell bionics as a step towards photosynthesis-independent hydrogen production
Low rate and limited duration are major challenges in photobiological hydrogen production. Here, the authors coat algal cells with a concentrically arranged shell comprising an ultra-thin Fe(III)-doped polypyrrole inner layer and outer exoskeleton of CaCO3, and achieve sustainable H2 production for over 200 days.
- Zhijun Xu
- , Jiarui Qi
- & Xin Huang
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Article
| Open Access
Macroevolutionary diversity of traits and genomes in the model yeast genus Saccharomyces
Here, the authors describe the geographies, hosts, substrates, and phylogenetic relationships for 1,794 Saccharomyces strains. They provide insight into the genetic and phenotypic diversity in the genus, not seen through prior work focused on the model species Saccharomyces cerevisiae.
- David Peris
- , Emily J. Ubbelohde
- & Chris Todd Hittinger
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Article
| Open Access
Manipulation 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 Access
Wax worm saliva and the enzymes therein are the key to polyethylene degradation by Galleria mellonella
The crucial first step in the biodegradation of polyethylene plastic is oxidation of the polymer. This has traditionally required abiotic pre-treatment, but now Bertocchini and colleagues report two wax worm enzymes capable of catalyzing this oxidation and subsequent degradation at room temperature.
- A. Sanluis-Verdes
- , P. Colomer-Vidal
- & F. Bertocchini
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Article
| Open Access
A 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 Access
Inducible expression of large gRNA arrays for multiplexed CRISPRai applications
CRISPR gene activation and inhibition has become a powerful synthetic tool for influencing the expression of native genes for foundational studies, cellular reprograming, and metabolic engineering. Here the authors demonstrate near leak-free, inducible expression of a polycistronic array containing up to 24 gRNAs from two orthogonal CRISPR/Cas systems.
- William M. Shaw
- , Lucie Studená
- & Rodrigo Ledesma-Amaro
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Article
| Open Access
Muconic 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 Access
An 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 Access
Unlocking 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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Comment
| Open AccessBottlenecks and opportunities for synthetic biology biosafety standards
The lack of innovative standards for biosafety in synthetic biology is an unresolved policy gap that limits many potential applications in synthetic biology. We argue that a massive support for standardization in biosafety is required for synthetic biology to flourish.
- Lei Pei
- , Michele Garfinkel
- & Markus Schmidt
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Article
| Open Access
Enhancing 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 Access
MiDAS 4: A global catalogue of full-length 16S rRNA gene sequences and taxonomy for studies of bacterial communities in wastewater treatment plants
Microbial communities are responsible for biological wastewater treatment. Here, Dueholm et al. generate more than 5 million high-quality, full-length 16S rRNA gene sequences from wastewater treatment plants across the world to construct a database with a comprehensive taxonomy, providing insights into diversity and function of these microbial communities.
- Morten Kam Dahl Dueholm
- , Marta Nierychlo
- & Per Halkjær Nielsen
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Article
| Open Access
Exploring a blue-light-sensing transcription factor to double the peak productivity of oil in Nannochloropsis oceanica
Microalgae are promising feedstock for oil production. The authors report that a transcription factor NobZIP77 can regulate oil synthesis by sensing the blue light, and explore these findings to greatly enhance oil productivity via genetic and process engineering in Nannochloropsis oceanica.
- Peng Zhang
- , Yi Xin
- & Jian Xu
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Article
| Open Access
Metabolic 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 Access
Synthetic glycans control gut microbiome structure and mitigate colitis in mice
Here, the authors characterize the gut microbiome fermentation properties and therapeutic potential of chemically diverse synthetic glycans (SGs), showing they promote specific shifts in taxonomic and metabolite profiles, and exhibit therapeutic benefits in mouse models of colonic inflammation, together implying SGs as a potential avenue to treat disease by modulating the composition and metabolites produced by the gut microbiome.
- Andrew C. Tolonen
- , Nicholas Beauchemin
- & Johan E. T. van Hylckama Vlieg
Resolving the metabolism of monolignols and other lignin-related aromatic compounds in Xanthomonas citri