Metabolic engineering articles within Nature Communications

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  • Perspective
    | Open Access

    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
  • Article
    | Open Access

    Antimicrobial peptides (AMPs) are promising next-generation antibiotics, but are difficult to produce due to the toxicity to bacterial hosts. Here, the authors report the utilization of transplastomic tobacco plants for AMPs production without cytotoxic effects via inducible expression systems and fusions to cleavable carrier protein.

    • Matthijs P. Hoelscher
    • , Joachim Forner
    •  & Ralph Bock
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Microbial production of cannabinoids promises a cheaper and more sustainable route to these important therapeutic molecules, but strain improvement and screening is challenging. Here, the authors develop a yeast-based Δ9-tetrahydrocannabinol (THC) biosensor for screening microbial mutant libraries.

    • William M. Shaw
    • , Yunfeng Zhang
    •  & Tom Ellis
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Although ginkgo terpenoids have been studied extensively for their pharmaceutical properties, knowledge on their biosynthesis remains limited. Here, the authors identify five multifunctional cytochrome P450s that catalyze the generation of the tert-butyl group and one of the lactone rings towards the biosynthesis of ginkgolides.

    • Victor Forman
    • , Dan Luo
    •  & Irini Pateraki
  • Article
    | Open Access

    Automated design and build processes can rapidly accelerate work in synthetic biology and metabolic engineering. Here the authors present Galaxy-SynBioCAD, a toolshed for synthetic biology, metabolic engineering, and industrial biotechnology that they use to build and execute Galaxy scientific workflows from pathway design to strain engineering through the automated generation of scripts driving robotic workstations.

    • Joan Hérisson
    • , Thomas Duigou
    •  & Jean-Loup Faulon
  • Article
    | Open Access

    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
  • Article
    | Open Access

    How triptonide is made in the medicinal plant Tripterygium wilfordii is largely unknown. Here, the authors report the identification and characterization of a suite of cytochrome P450s and show their function in catalyzing the formation of triptonide from miltriadiene in tobacco and baker’s yeast.

    • Nikolaj Lervad Hansen
    • , Louise Kjaerulff
    •  & Johan Andersen-Ranberg
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Optimization of biological networks is often limited by wet lab labor and cost, and the lack of convenient computational tools. Here, aimed at democratization and standardization, the authors describe METIS, a modular and versatile active machine learning workflow with a simple online interface for the optimization of biological target functions with minimal experimental datasets.

    • Amir Pandi
    • , Christoph Diehl
    •  & Tobias J. Erb
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Rubusoside and rebaudiosides are considered the next generation of sugar substitutes. In this article, the authors report the engineering of Saccharomyces cerevisiae, remodelling the complex metabolic networks by a modular engineering approach, obtaining rubusoside and rebaudiosides at titers of around 1.4 g/L and 100 mg/L, respectively.

    • Yameng Xu
    • , Xinglong Wang
    •  & Long Liu
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Unlike Panax species, which can produce dammarane-type saponins, Aralia elata can only synthesize oleananetype saponins. Here, the authors reveal that the loss of the dammaranediol synthase-encoding gene and tandem duplication of triterpene biosynthetic genes drive structural divergences of saponins between the two genera.

    • Yu Wang
    • , He Zhang
    •  & Yuhua Li
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Producing plant secondary metabolites by microbes is limited by the known enzymatic reactions. Here, the authors apply machine learning to predict missing link enzymes of benzylisoquinoline alkaloid (BIA) biosynthesis in Papaver somniferum, and validate the specialized activities through heterologous production.

    • Christopher J. Vavricka
    • , Shunsuke Takahashi
    •  & Tomohisa Hasunuma
  • Article
    | Open Access

    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
  • Article
    | Open Access

    There are a lack of eukaryotic biosensors specific for branched-chain amino acid (BCAA)-derived products. Here the authors report a genetically encoded biosensor for BCAA metabolism based on the Leu3p transcriptional regulator; they use this to monitor yeast production of isobutanol and isopentanol.

    • Yanfei Zhang
    • , Jeremy D. Cortez
    •  & José L. Avalos
  • Article
    | Open Access

    Worldwide pandemics of obesity and diabetes prompt an urgent need for new approaches to their prevention and cure. Here the authors present a CRISPR-based strategy that enhances the therapeutic potential of human adipocytes when implanted in obese mice.

    • Emmanouela Tsagkaraki
    • , Sarah M. Nicoloro
    •  & Michael P. Czech
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Rational design of enzymes with new or improved properties is rarely straightforward, and artificial selection pressure approaches that link an improvement in the target to cell growth are an alternative. Here, the authors show that diverse enzymes sharing the ubiquitous cofactor NAD(P)+ can substitute for defective NAD+ regeneration, representing a very broadly-applicable artificial selection.

    • Lara Sellés Vidal
    • , James W. Murray
    •  & John T. Heap
  • Article
    | Open Access

    The testing of engineered enzymes represents a bottleneck. Here the authors report a screening method combining microfluidics and mass spectrometry, to map the catalysis of a mutated enzyme, characterise the range of products generated and recover the sequences of variants with desired activities.

    • Linfeng Xu
    • , Kai-Chun Chang
    •  & Adam R. Abate
  • Article
    | Open Access

    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
  • Article
    | Open Access

    Isoflavonoids are a class of industrially important plant natural products, but their low abundance and structural complexity limits their availability. Here, the authors engineer Saccharomyces cerevisiae metabolism to become a platform for efficient production of daidzein which is core chemical scaffold for isoflavonoid biosynthesis, and show its application for production of bioactive glucosides from glucose.

    • Quanli Liu
    • , Yi Liu
    •  & Jens Nielsen
  • Article
    | Open Access

    Fatty acyl reductases (FARs) are critical enzymes in the biosynthesis of fatty alcohols and have the ability to directly acces acyl-ACP substrates. Here, authors couple machine learning-based protein engineering framework with gene shuffling to optimize a FAR for the activity on acyl-ACP and improve fatty alcohol production.

    • Jonathan C. Greenhalgh
    • , Sarah A. Fahlberg
    •  & Philip A. Romero
  • Comment
    | Open Access

    Synthetic biology has brought about a conceptual shift in our ability to redesign microbial metabolic networks. Combining metabolic pathway-modularization with growth-coupled selection schemes is a powerful tool that enables deep rewiring of the cell factories’ biochemistry for rational bioproduction.

    • Enrico Orsi
    • , Nico J. Claassens
    •  & Steffen N. Lindner