Featured
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| Open AccessHyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis
3-Hydroxypropionic acid (3HP) is an important platform chemical. Here, the authors engineer Halomonas bluephagenesis by deleting newly identified degradation pathway and balancing redox state to achieve high level production of 3HP and its copolymer under open and unsterile conditions.
- Xiao-Ran Jiang
- , Xu Yan
- & Guo-Qiang Chen
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Article
| Open AccessComplex yeast–bacteria interactions affect the yield of industrial ethanol fermentation
Industrial sugarcane ethanol fermentations are accomplished by a microbial community dominated by S. cerevisiae and co-occurring bacteria. Here, the authors investigate how microbial community composition contributes to community function and reveal the role of acetaldehyde in improving yeast growth rate and ethanol production.
- Felipe Senne de Oliveira Lino
- , Djordje Bajic
- & Morten Otto Alexander Sommer
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Article
| Open AccessEngineered yeast genomes accurately assembled from pure and mixed samples
The cost and complexity of whole genome sequencing limits its use in identifying and validating sequences used for genetic engineering and synthetic biology. Here the authors present Prymetime, an integrated workflow to sequence engineered strains and identify engineering in metagenomes.
- Joseph H. Collins
- , Kevin W. Keating
- & Eric M. Young
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Article
| Open AccessComplete biosynthesis of a sulfated chondroitin in Escherichia coli
Chondroitin sulfate (CS) is a type of sulfated glycosaminoglycan that is manufactured by extraction from animal tissues for the treatment of osteoarthritis and in drug delivery applications. Here, the authors report the development of single microbial cell factories capable of compete, one-step biosynthesis of animal-free CS production in E. coli.
- Abinaya Badri
- , Asher Williams
- & Mattheos A. G. Koffas
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Article
| Open AccessCas12a-assisted precise targeted cloning using in vivo Cre-lox recombination
Direct cloning of biosynthetic gene clusters is difficult due to their size and repetitive nature. Here, the authors present CAPTURE, which uses Cas12a and in vivo Cre-lox recombination for efficient cloning of gene clusters up to 113 kb, and demonstrate how this method can be used for large-scale discovery of novel natural products.
- Behnam Enghiad
- , Chunshuai Huang
- & Huimin Zhao
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Article
| Open AccessAuxin-mediated protein depletion for metabolic engineering in terpene-producing yeast
Loss-of-function experiments are used in metabolic engineering to understand and optimise metabolism. Here, the authors apply auxin inducible protein degradation to test different metabolic engineering strategies for improved terpenoid production in yeast.
- Zeyu Lu
- , Bingyin Peng
- & Claudia E. Vickers
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Article
| Open AccessMicrobial production of multiple short-chain primary amines via retrobiosynthesis
Short-chain primary amines (SCPAs) are industrially important compounds that are commonly produced under harsh synthetic conditions. Here, the authors report a combination of retrobiosynthesis and precursor selection step for design of biosynthetic pathways leading to production of SCPAs, using valine decarboxylase-expressing Escherichia coli strains.
- Dong In Kim
- , Tong Un Chae
- & Sang Yup Lee
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Comment
| Open AccessSynthetic biology 2020–2030: six commercially-available products that are changing our world
Synthetic biology will transform how we grow food, what we eat, and where we source materials and medicines. Here I have selected six products that are now on the market, highlighting the underlying technologies and projecting forward to the future that can be expected over the next ten years.
- Christopher A. Voigt
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Article
| Open AccessSynthesis of high-titer alka(e)nes in Yarrowia lipolytica is enabled by a discovered mechanism
Alka(e)nes with chain lengths in C5-C23 range are ideal fuel components. Here, the authors report that high-titer production of alak(e)nes in pathway engineered Yarrowia lipolytica, which is enabled by the finding that acyl-CoA is another substrate of fatty acid photodecarboxylase (FAP).
- Jingbo Li
- , Yongshuo Ma
- & Gregory Stephanopoulos
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Article
| Open AccessPhotosynthetic hydrogen production by droplet-based microbial micro-reactors under aerobic conditions
The development of techniques capable of orchestrating the assembly of living cells into multicellular ensembles with synergistic and function is challenge. Here, the authors construct algal or algal/bacterial cells-based core shell-like structure based on aqueous two-phase system for synergic photosynthetic H2 production.
- Zhijun Xu
- , Shengliang Wang
- & Stephen Mann
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Article
| Open AccessProton-enabled activation of peptide materials for biological bimodal memory
The structural programmability and functionality of peptide materials can be leverage for various next-generation devices such as non-volatile memories. The authors report a proton-coupled mechanism in tyrosine-rich peptides for realizing multimodal memory devices.
- Min-Kyu Song
- , Seok Daniel Namgung
- & Jang-Yeon Kwon
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Article
| Open AccessSpace station biomining experiment demonstrates rare earth element extraction in microgravity and Mars gravity
Rare earth elements are used in electronics, but increase in demand could lead to low supply. Here the authors conduct experiments on the International Space Station and show microbes can extract rare elements from rocks at low gravity, a finding that could extend mining potential to other planets.
- Charles S. Cockell
- , Rosa Santomartino
- & René Demets
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Article
| Open AccessTitrating bacterial growth and chemical biosynthesis for efficient N-acetylglucosamine and N-acetylneuraminic acid bioproduction
An imbalance between cell growth and bioproduction of engineered microbes often reduces production efficiency. Here, the authors report genetic code expansion-based cell growth and biosynthesis balance engineering to achieve high levels production of N-acetylglucosamine in E. coli and N-acetylneuraminic acid in B. subtilis.
- Rongzhen Tian
- , Yanfeng Liu
- & Jian Chen
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Article
| Open AccessEngineering and application of a biosensor with focused ligand specificity
Transcriptional biosensors represent powerful tools for the screening of vast strain libraries, but the broad ligand specificity of some transcriptional regulators (TRs) can prohibit such applications. Here authors present the engineering of a LysG-based biosensor with a focused ligand specificity to isolate L-histidine-producing strains.
- Dennis Della Corte
- , Hugo L. van Beek
- & Jan Marienhagen
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Article
| Open AccessSynthetic microbial communities of heterotrophs and phototrophs facilitate sustainable growth
Successful application of microbial community for bioproduction relies on the selection of appropriate heterotroph and phototroph partners. Here, the authors construct community metabolic models to guide strain selection and experimentally validate metabolic exchanges that sustain the heterotrophs in minimal media.
- Cristal Zuñiga
- , Tingting Li
- & Karsten Zengler
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Article
| Open AccessRational flux-tuning of Halomonas bluephagenesis for co-production of bioplastic PHB and ectoine
Halomonas bluephagenesis is a halophilic platform bacterium for next generation industrial biotechnology. Here, the authors employ a stimulus response-based flux-tuning method for coproduction of bioplastic PHB and ectoine under open unsterile and continuous growth conditions.
- Hong Ma
- , Yiqing Zhao
- & Guo-Qiang Chen
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Article
| Open AccessEliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum
Bioproduction of hyaluronan needs increases in yield and greater diversity of the molecular weights. Here, the author increases hyaluronan production and diversifies the molecular weights through engineering the hyaluronan biosynthesis pathway and disruption of Corynebacterium glutamicum encapsulation caused by secreted hyaluronan.
- Yang Wang
- , Litao Hu
- & Zhen Kang
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Article
| Open AccessLight-powered Escherichia coli cell division for chemical production
Manipulation of genes controlling microbial shapes can affect bio-production. Here, the authors employ an optogenetic method to realize dynamic morphological engineering of E. coli replication and division and show the increased production of acetoin and poly(lactate-co-3-hydroxybutyrate).
- Qiang Ding
- , Danlei Ma
- & Xiulai Chen
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Article
| Open AccessStress-induced expression is enriched for evolutionarily young genes in diverse budding yeasts
Fermentation parameters of industrial processes are often not the ideal growth conditions for industrial microbes. Here, the authors reveal that young genes are more responsive to environmental stress than ancient genes using a new gene age assignment method and provide targeted genes for metabolic engineering.
- Tyler W. Doughty
- , Iván Domenzain
- & John P. Morrissey
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Article
| Open AccessEnhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase
Malate dehydrogenase (MDH) is one of the key enzymes for succinic acid (SA) bioproduction. Here, the authors report biochemical and structural analyses of various MDHs to reveal amino acids influencing the specific activity and susceptibility to substrate inhibition, and achieve industrial-level SA production.
- Jung Ho Ahn
- , Hogyun Seo
- & Sang Yup Lee
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Article
| Open AccessDevelopment of a thermophilic coculture for corn fiber conversion to ethanol
Corn fiber is a difficult feedstock to utilize due to its recalcitrant hemicellulose. Here, the authors characterize the recalcitrant structures, isolate a new bacterium to consume the hemicellulose, identify its enzymes, and show the benefit with increased conversion of corn fiber to ethanol.
- Dhananjay Beri
- , William S. York
- & Christopher D. Herring
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Article
| Open AccessSynthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones
Combining genome mining and heterologous expression in a genetically tractable host can lead to bioactive natural products discovery and production. Here, the authors employ this strategy for new decalin-containing diterpenoid pyrenes production by expressing native, extended, and shunt pathways in Aspergillus oryzae.
- Kento Tsukada
- , Shono Shinki
- & Teigo Asai
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Article
| Open AccessPooled CRISPRi screening of the cyanobacterium Synechocystis sp PCC 6803 for enhanced industrial phenotypes
Developing cyanobacteria as CO2-neutral cell factories relies on the knowledge of the regulation mechanisms for growth and metabolism. Here, the authors develop an inducible CRISPRi gene repression library in Synechocystis sp. PCC 6803 and screens genes potentially affecting growth and L-lactate tolerance and production.
- Lun Yao
- , Kiyan Shabestary
- & Elton P. Hudson
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Article
| Open AccessA severe leakage of intermediates to shunt products in acarbose biosynthesis
Biosynthetic mechanism for the type 2 diabetes treatment drug acarbose is not fully revealed. Here, the authors show that shunt pathways and inefficient amino-deoxyhexose biosynthesis lead to 1-epi-valienol and valienol accumulation, and minimizing the flux to these shunt products can increase acarbose titer in Actinoplanes species.
- Qinqin Zhao
- , Yuchang Luo
- & Zixin Deng
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Article
| Open AccessA comparative genomics study of 23 Aspergillus species from section Flavi
Aspergillus fungi classified within the section Flavi include harmful and beneficial species. Here, Kjærbølling et al. analyse the genomes of 23 Flavi species, showing high genetic diversity and potential for synthesis of over 13,700 CAZymes and 1600 secondary metabolites.
- Inge Kjærbølling
- , Tammi Vesth
- & Mikael R. Andersen
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Article
| Open AccessTowards a fully automated algorithm driven platform for biosystems design
Existing efforts have been focused on one of the elements in the automation of the design, build, test, and learn (DBTL) cycle for biosystems design. Here, the authors integrate a robotic system with machine learning algorithms to fully automate the DBTL cycle and apply it in optimizing the lycopene biosynthetic pathway.
- Mohammad HamediRad
- , Ran Chao
- & Huimin Zhao
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Article
| Open AccessDesigning yeast as plant-like hyperaccumulators for heavy metals
Existing heavy metal bioremediation systems are mainly based on plants, which require long growing time in specific conditions. Here, the authors mimic the characteristics of plant hyperaccumulators to engineer more tractable baker’s yeast and achieve 10–100-fold higher accumulation of chromium, arsenic, or cadmium.
- George L. Sun
- , Erin. E. Reynolds
- & Angela M. Belcher
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Article
| Open AccessRewiring carbon metabolism in yeast for high level production of aromatic chemicals
Microbial production of aromatic amino acid (AAA)-derived chemicals remains an outstanding metabolic engineering challenge. Here, the authors engineer baker’s yeast for high levels p-coumaric acid production by rewiring the central carbon metabolism and channeling more flux to the AAA biosynthetic pathway.
- Quanli Liu
- , Tao Yu
- & Yun Chen
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Article
| Open AccessGalactose to tagatose isomerization at moderate temperatures with high conversion and productivity
Production of tagatose, a sugar substitute, by isomerization of galactose suffers from unfavorable enzymatic kinetics, low enzyme stability, and low equilibrium constant. Here, the authors simultaneously overcome these limitations by encapsulating l-arabinose isomerase in permeabilized Lactobacillus plantarum.
- Josef R. Bober
- & Nikhil U. Nair
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Article
| Open AccessDevelopment of a longevous two-species biophotovoltaics with constrained electron flow
Power densities of existing microbial biophotovoltaics (BPV) are low and unendurable. Here, the authors develop a BPV based on d-lactate mediated microbial consortium, which can generate an average power density of 135 mW·m−2 for over 40 days in a spatial-temporal separation setup with medium replenishment.
- Huawei Zhu
- , Hengkai Meng
- & Yin Li
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Article
| Open AccessModular enzyme assembly for enhanced cascade biocatalysis and metabolic flux
Metabolic enzymes often form supramolecular complexes to improve product yield. Here the authors use short peptide tags to create scaffold-free assemblies and synthetic metabolic nodes.
- Wei Kang
- , Tian Ma
- & Tiangang Liu
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Article
| Open AccessProduction of zosteric acid and other sulfated phenolic biochemicals in microbial cell factories
Toxicity and limited solubility inhibits the biological production of many organic compounds. Here the authors metabolically engineer sulfate uptake and activation in order to produce sulfate esters of phenolic compounds, such as zosteric acid, thereby addressing these issues.
- Christian Bille Jendresen
- & Alex Toftgaard Nielsen
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Article
| Open AccessPolyunsaturated fatty acid production by Yarrowia lipolytica employing designed myxobacterial PUFA synthases
Sustainable sources are needed to meet the demand for long-chain polyunsaturated fatty acids. Here the authors construct an artificial biosynthetic gene cluster in Y. lipolytica capable of producing a high concentration of PUFAs.
- Katja Gemperlein
- , Demian Dietrich
- & Rolf Müller
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Article
| Open AccessVibrio sp. dhg as a platform for the biorefinery of brown macroalgae
Brown macroalgae is a good candidate feedstock for biorefinery, but the major carbohydrate alginate cannot be digested by current industrial microbes. Here, the authors isolate Vibrio sp. dhg and engineer it to produce value-added biochemicals from alginate using newly developed genetic tools.
- Hyun Gyu Lim
- , Dong Hun Kwak
- & Gyoo Yeol Jung
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Review Article
| Open AccessSynthetic biology strategies for microbial biosynthesis of plant natural products
Engineering microbial cell factories for the production of useful plant natural products (PNPs) is a resource-conserving and environmentally-friendly synthesis route. Here, the authors review recent developments that enable engineering of hosts, pathways, and enzymes to make PNPs and PNP derivatives.
- Aaron Cravens
- , James Payne
- & Christina D. Smolke
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Article
| Open AccessCopper-containing glass ceramic with high antimicrobial efficacy
Copper is well known for its high antimicrobial efficacy; however, cost, appearance and metallic properties limit application. Here the authors describe a stable, water dispersible copper-glass ceramic powder with long-term antimicrobial activity as an additive for antimicrobial surfaces.
- Timothy M. Gross
- , Joydeep Lahiri
- & Michael J. Snyder
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Article
| Open AccessEngineered microbial biofuel production and recovery under supercritical carbon dioxide
End-product toxicity, culture contamination, and energy efficient product recovery are long-standing issues in bioprocessing. Here, the authors address these problems using a fermentation strategy that combines microbial production of branched alcohols with supercritical carbon dioxide extraction.
- Jason T. Boock
- , Adam J. E. Freedman
- & Janelle R. Thompson
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Article
| Open AccessBiocatalytic production of adiponitrile and related aliphatic linear α,ω-dinitriles
Typically, preparation of the polymer precursors α,ω-dinitriles requires hydrogen cyanide. Here, the authors use aldoxime hydratase to produce adiponitrile and related aliphatic linear dinitriles under ambient conditions starting from readily available substrates without needing hydrogen cyanide.
- Tobias Betke
- , Manuel Maier
- & Harald Gröger
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Article
| Open AccessEngineering Saccharomyces cerevisiae for co-utilization of d-galacturonic acid and d-glucose from citrus peel waste
Pectin-rich agricultural byproducts are ideal feedstocks for biobased chemicals production. Here, the authors engineer the yeast, S. cerevisiae, in several steps to co-utilize d-galacturonic acid and d-glucose and demonstrate the potential of producing meso-galactaric acid from industrial orange peel.
- Ryan J. Protzko
- , Luke N. Latimer
- & John E. Dueber
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Article
| Open AccessA single Gal4-like transcription factor activates the Crabtree effect in Komagataella phaffii
Aerobic ethanol production, a phenomenon referred as Crabtree effect, allows yeast to outcompete other microorganisms in sugar rich environments. Here, the authors show that overexpression of a Gal4-like transcription factor can transform Komagataella phaffii from Crabtree effect negative to positive.
- Özge Ata
- , Corinna Rebnegger
- & Diethard Mattanovich
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Article
| Open AccessMetabolic engineering of Escherichia coli for de novo biosynthesis of vitamin B12
Vitamin B12 is an essential nutrient with limited natural sources. Here the authors transfer 28 pathway synthesis genes from several bacteria including R. capsulatus to E. coli and, using metabolic engineering and optimised fermentation conditions, achieve high yields.
- Huan Fang
- , Dong Li
- & Dawei Zhang
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Article
| Open AccessShort-chain ketone production by engineered polyketide synthases in Streptomyces albus
Mutating natural enzymes is effective in broadening the substrate or product range, but generally leads to reduced titers. Here the authors engineer hybrid polyketide synthases for efficient production of short-chain ketones from plant biomass hydrolysates in Streptomyces, which can increase the octane of gasoline.
- Satoshi Yuzawa
- , Mona Mirsiaghi
- & Jay D. Keasling
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Article
| Open AccessTowards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis
The bacterial diterpene synthase CotB2 catalyses the cyclisation of geranylgeranyl diphosphate to cyclooctat-9-en7-ol. Here the authors present various CotB2 structures including a trapped abrupt reaction product that were used for molecular dynamic simulations and allowed them to model all intermediates along the reaction cascade.
- Ronja Driller
- , Sophie Janke
- & Bernhard Loll
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Article
| Open AccessReviving the Weizmann process for commercial n-butanol production
Organic solvent n-butanol is produced mainly by petrochemical method. Here, the authors revive the historical Weizmann process by engineering Clostridium acetobutylicum strain and developing low pressure distillation and high cell density cultures for n-butanol continuous production at high-yield titer and productivity.
- Ngoc-Phuong-Thao Nguyen
- , Céline Raynaud
- & Philippe Soucaille
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Article
| Open AccessGlobal rewiring of cellular metabolism renders Saccharomyces cerevisiae Crabtree negative
Reducing aerobic ethanol production, a phenomenon referred to as the Crabtree effect, may open up new perspectives for using yeast as a cell factory. Here, the authors turn the Crabtree-positive yeast into Crabtree negative by combined engineering of cytosolic acetyl-CoA metabolism and mutating the RNA polymerase II mediator complex.
- Zongjie Dai
- , Mingtao Huang
- & Jens Nielsen
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Article
| Open AccessSensor-regulator and RNAi based bifunctional dynamic control network for engineered microbial synthesis
Engineering dynamic control can improve microbial production of target chemicals. Here, the authors design a sensor-regulator and RNAi based bifunctional dynamic control network that can simultaneously and independently turn up and down cellular metabolism for engineered muconic acid production in E. coli.
- Yaping Yang
- , Yuheng Lin
- & Yajun Yan
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Article
| Open AccessTools for engineering coordinated system behaviour in synthetic microbial consortia
The engineering of synthetic microbial communities necessitates the use of synthetic, orthogonal cell-to-cell communication channels. Here the authors present a library of characterised AHL-receiver devices and a software tool for the automatic identification of non-interfering chemical communication channels.
- Nicolas Kylilis
- , Zoltan A. Tuza
- & Karen M. Polizzi
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Comment
| Open AccessSCRaMbLEing to understand and exploit structural variation in genomes
- Jan Steensels
- , Anton Gorkovskiy
- & Kevin J. Verstrepen
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Article
| Open AccessMultidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli
Achieving high titer yield and productivity of target chemicals in industrial organism depends on multidimensional pathway optimization. Here, the authors use a refined modular method called multidimensional heuristic process to improve production of astaxanthin, nerolidol and linalool in E. coli.
- Congqiang Zhang
- , Vui Yin Seow
- & Heng-Phon Too