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Biomanufacturing can be scaled up with technological innovation, feedstock supply optimization and proper infrastructure, argues Sang Yup Lee.

To mark the inaugural issue of Nature Chemical Engineering, we asked a collection of scientists working in different branches of chemical engineering to share their perspectives on the challenges and opportunities that lie ahead for their respective fields.

As soft electronic waste becomes an urgent concern, biodegradable yet high-performance devices are emerging as a promising solution. Here the authors fabricate durable and multifunctional soft robotic fingers in which both polymers and inorganic electronics are fully compostable.

The extracellular matrix is remodeled to form complex interconnected network structures that regulate stem cell behaviors. Here, the authors modulate extracellular matrix-like networks using magnetic nano-blockers, adjusting stem cell behavior by changing ligand inter-cluster connectivity. This dynamic system provides new insights into cell-material interactions for tissue regeneration.

Microbes have already been engineered to produce diesel fuels, and now the microbial production of components of petrol (gasoline) including short-chain alkanes has been achieved using Escherichia coli strains metabolically engineered with components of fatty acid biosynthesis pathways.

In-situ cryo-electron microscopy in thin amorphous ice films and ice-dynamics simulations reveal polymorph-dependent growth kinetics of nanoscale ice crystals. Hetero-crystalline ice exhibits anisotropic growth: fast-growing facets are associated with low-density interfaces, driving tetrahedral ordering of interfacial H₂O molecules and accelerating ice growth.

Regulation of ice growth and ice growth inhibition are critical and different materials mimicking anti freeze proteins or ice binding surfaces have been developed. Here, the authors combine both concepts in a hyperbranched polyglycerols to change the ice growth activity.

Commercial lutein is mainly extracted from marigold flowers, which is an inefficient process. Now a gram-per-litre-scale process for microbial production of lutein is reported using metabolically engineered Corynebacterium glutamicum. By integrating flux optimization, engineered cytochrome P450 enzymes, electron-channelling scaffolds and fermentation strategies, this approach provides a microbial platform for lutein biosynthesis.

Terephthalic acid (TPA) is an important commodity chemical typically produced from the oxidation of fossil fuel-derivedp-xylene (pX) at high temperature and pressure. Here the authors report an engineered Escherichia coli strain that can transform pX into TPA with a high conversion yield.

Functional annotation of open reading frames in microbial genomes remains substantially incomplete. Here, Kim et al. present a deep learning model that utilizes transformer layers as a neural network architecture to predict specific catalytic functions for enzyme-encoding genes of unknown function.

Glucose uptake is the initial step in cellular metabolism, and its uptake rate directly determines the overall metabolic flow. Here the authors develop a set of programmable bifunctional biosensors for real-time monitoring of glucose uptake rates and dynamic dual control of glucose uptake and central metabolism.

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.

Eukaryotic cytochrome P450s (P450s) are often required for the biosynthesis of natural products, but their performance in bacteria is usually reduced. Now, scaffold enzymes bring eukaryotic P450s and a reductase in close proximity for efficient electron channelling, increasing the production of natural products in Escherichia coli.

An analysis of gut microbiomes of patients with non-small-cell lung cancer reveals an association between Bifidobacterium bifidum abundance and response to cancer therapy. In murine models of syngeneic tumours, administration of commercial B. bifidum strains synergizes with immune checkpoint blockade to reduce tumour burden, but the therapeutic potential of B. bifidum is affected by strain-level variation.

Biobased polymers provide a sustainable alternative to petroleum-based plastics. In this study, the authors engineered Escherichia coli to biosynthesize poly(ester amide)s with customizable amino acids, expanding options for renewable, biobased polymer production.

Constructing an efficient microbial cell factory still requires exploring and selecting various host strains, as well as identifying the best-suited metabolic engineering strategies, which demand significant time, effort, and costs. Here the authors calculate the maximum yields of 235 bio-based chemicals in 5 different microbes, evaluated heterologous reactions and cofactor swaps, and predicted engineering strategies, providing a comprehensive resource for systems metabolic engineering.

Benzyl acetate is a valuable aromatic ester compound used in flavorings and fragrances. Now, a microbial approach is developed to produce benzyl acetate from d-glucose using metabolically engineered Escherichia coli strains and exploiting delayed co-culture strategies.

In this Review, the authors discuss how artificial intelligence can aid microbial gene function discovery.

n-Butanol is a valuable biofuel that can be produced industrially by bacterial fermentation. Here the authors uncover a redox-switch within Clostridium acetobutylicum’s thiolase—a key enzyme involved in n-butanol biosynthesis—that controls the rate of fermentative butanol production.

Biotechnology is a central focus in efforts to provide sustainable solutions for the provision of fuels, chemicals and materials. On the basis of a recent open discussion, we summarize the development of this field, highlighting the distinct but complementary approaches provided by metabolic engineering and synthetic biology for the creation of efficient cell factories to convert biomass and other feedstocks to desired chemicals.

Adenosylcobalamin (AdoCbl) is an essential vitamin whose production is limited to bacterial fermentation. Here, the authors report an alternative method for the synthesis of AdoCbl based on a cell-free reaction system integrating more than 30 biocatalytic reactions to produce AdoCbl from 5-aminolevulinic acid.

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.

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.

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.

CRISPR prime editing enables double-strand break free engineering of the genome. Here the authors present a toolkit for prime editing in E. coli.

Microbial production of haem for applications in healthcare and food supplement industry requires high-performing strains. Here, Lee and co-workers report secretory production of free haem by metabolically engineered Escherichia coli strains to produce up to 239 mg l⁻¹ total haem.

Utilization of structural proteins with intrinsically disordered regions enables the formation of membraneless organelles in Escherichia coli through liquid–liquid phase separation, as well as their functionalization with active enzymes.

Some antibiotic resistance genes found in pathogenic bacteria might derive from antibiotic-producing actinobacteria. Here, Jianget al. provide bioinformatic and experimental evidence supporting this hypothesis, and propose a specific mechanism for the transfer of these genes between bacterial phyla.

The amino acid, L-arginine, has important applications in the food, pharmaceutical and cosmetics industries. Here the authors systematically engineer a Corynebacterium glutamicum strain for the production of L-arginine, and show that their metabolic engineering approach can be used for the industrial production of valuable chemicals.

Arrays of bioresorbable, highly doped silicon electrodes with multiplexing capabilities are used as electrocorticography sensors to perform in vivo, reliable acute and chronic recordings for up to one month before dissolving in the body.

Fermentative production of aromatic polyesters from glucose has been unsuccessful. Here, the authors achieve the objective by one-step fermentation of metabolically engineered E. coli expressing a isocaprenoyl-CoA:2-hydroxyisocaproate CoA-transferase and an evolved polyhydroxyalkanoate synthase.

Optimization of triacylglycerol production in the oleaginous bacterium Rhodococcus opacus followed by pathway engineering enables the enhanced production of free fatty acids, fatty acid ethyl esters and long-chain hydrocarbons from glucose.

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.

The design and implementation of a high-yielding enzymatic route to 1,4-butanediol—a compound not known to be produced naturally—provides a compelling example of how metabolic engineering can be harnessed for the microbial conversion of carbohydrate feedstocks to desired small molecules.