Relieving metabolic burden to improve robustness and bioproduction by industrial microorganisms

Biotechnology Advances, Год журнала: 2024, Номер 74, С. 108401 - 108401

Опубликована: Июнь 27, 2024

Metabolic burden is defined by the influence of genetic manipulation and environmental perturbations on distribution cellular resources. The rewiring microbial metabolism for bio-based chemical production often leads to a metabolic burden, followed adverse physiological effects, such as impaired cell growth low product yields. Alleviating imposed undesirable changes has become an increasingly attractive approach constructing robust factories. In this review, we provide brief overview engineering, focusing specifically recent developments strategies diminishing while improving robustness yield. A variety examples are presented showcase promise engineering in facilitating design construction Finally, challenges limitations encountered discussed.

Язык: Английский

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A new flavor of synthetic yeast communities sees the light

mBio, Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

ABSTRACT No organism is an island: organisms of varying taxonomic complexity, including genetic variants a single species, can coexist in particular niches, cooperating for survival while simultaneously competing environmental resources. In recent years, synthetic biology strategies have witnessed surge efforts focused on creating artificial microbial communities to tackle pressing questions about the complexity natural systems and interactions that underpin them. These engineered ecosystems depend number nature their members, allowing complex cell communication designs recreate create diverse interest. Due its experimental simplicity, budding yeast Saccharomyces cerevisiae has been harnessed establish mixture varied populations with potential explore ecology, metabolic bioprocessing, biosensing, pattern formation. Indeed, enable advanced molecule detection dynamics logic operations. Here, we present concise overview state-of-the-art, highlighting examples exploit optogenetics manipulate, through light stimulation, key phenotypes at community level, unprecedented spatial temporal regulation. Hence, envision bright future where application optogenetic approaches (optoecology) illuminates intricate drives innovations engineering strategies.

Язык: Английский

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Harnessing microbial division of labor for biomanufacturing: a review of laboratory and formal modeling approaches

Critical Reviews in Biotechnology, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Фев. 19, 2025

Bioprocess industries aim to meet the increasing demand for product complexity by designing enhanced cellular and metabolic capabilities host. Monocultures, standard biomanufacturing workhorses, are often restricted in their capability these demands, solution involves genetic modification of Synthetic microbial communities a promising alternative monocultures because they exhibit division labor, enabling efficient resource utilization pathway modularity. This specialization minimizes burden enhances robustness perturbations, providing competitive advantage. Despite this potential, biotechnological or bioprocessing applications remains limited. The recent emergence new innovative community design tools strategies, particularly those harnessing holds promise change outlook. Understanding interactions governing natural can be used identify complementary partners, informing synthetic design. Therefore, we consider engineering labor as viable accelerate progress field. review presents current understanding how enable information perform tasks otherwise unfeasible individual organisms. We then evaluate laboratory formal modeling approaches specifically developed to: elucidate physiology, guide experimental design, improve our complex assisting By synthesizing insights, present comprehensive framework that advances use applications.

Язык: Английский

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De novo biosynthesis of plant lignans by synthetic yeast consortia

Nature Chemical Biology, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Язык: Английский

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A new era of synthetic biology—microbial community design

Synthetic Biology, Год журнала: 2024, Номер 9(1)

Опубликована: Янв. 1, 2024

Abstract Synthetic biology conceptualizes biological complexity as a network of parts, devices, and systems with predetermined functionalities has had revolutionary impact on fundamental applied research. With the unprecedented ability to synthesize transfer any DNA RNA across organisms, scope synthetic is expanding being recreated in previously unimaginable ways. The field matured level where highly complex networks, such artificial communities can be constructed. In parallel, computational became an integral part studies, models aiding unravelling escalating emerging properties phenomena. However, there still vast untapped potential for complete integration modelling into design process, presenting exciting opportunities scientific advancements. Here, we first highlight most recent advances computer-aided microbial communities. Next, propose that benefit from organism-free modular approach places its emphasis modules organismal function towards multispecies We argue shift perspective single organism–centred approaches emphasizing functional contributions organisms within community. By assembling using mathematical descriptions parts circuits, tailor fulfil specific roles This aligns strategies presents possibilities Graphical

Язык: Английский

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Higher-order interactions and emergent properties of microbial communities: The power of synthetic ecology

Heliyon, Год журнала: 2024, Номер 10(14), С. e33896 - e33896

Опубликована: Июль 1, 2024

Humans have long relied on microbial communities to create products, produce energy, and treat waste. The microbiota residing within our bodies directly impacts health, while the soil rhizosphere microbiomes influence productivity of crops. However, complexity diversity make them challenging study difficult develop into applications, as they often exhibit emergence unpredictable higher-order phenomena. Synthetic ecology aims at simplifying by constituting synthetic or semi-natural with reduced that become easier analyze. This strategy combines methodologies simplify existing complex systems (top-down approach) build system from its constituent components (bottom-up approach). Simplified are studied understand how interactions among populations shape behavior community model predict their response external stimuli. By harnessing potential through a multidisciplinary approach, we can advance knowledge ecological concepts address critical public agricultural, environmental issues more effectively.

Язык: Английский

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Synthetic Microbial Ecology: Engineering Habitats for Modular Consortia

Journal of Applied Microbiology, Год журнала: 2024, Номер 135(7)

Опубликована: Июнь 27, 2024

Abstract Microbiomes, the complex networks of micro-organisms and molecules through which they interact, play a crucial role in health ecology. Over at least past two decades, engineering biology has made significant progress, impacting bio-based industry, health, environmental sectors; but only recently begun to explore microbial ecosystems. The creation synthetic communities presents opportunities help us understand dynamics wild ecosystems, learn how manipulate interact with existing microbiomes for therapeutic other purposes, create entirely new capable undertaking tasks industrial biology. Here, we describe ecosystems can be constructed controlled, focusing on available methods interaction mechanisms facilitate regulation community composition output. While experimental decisions are dictated by intended applications, vast number tools suggests great opportunity researchers develop diverse array novel

Язык: Английский

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Synthetic Biology of Natural Products Engineering: Recent Advances Across the Discover–Design–Build–Test–Learn Cycle

ACS Synthetic Biology, Год журнала: 2024, Номер 13(9), С. 2684 - 2692

Опубликована: Авг. 20, 2024

Advances in genome engineering and associated technologies have reinvigorated natural products research. Here we highlight the latest developments field across discover–design–build–test–learn cycle of bioengineering, from recent progress computational tools for AI-supported mining, enzyme pathway engineering, compound identification to novel host systems new techniques improving production levels, place these trends context responsible research innovation, emphasizing importance anticipatory analysis at early stages process development.

Язык: Английский

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Engineered cross-feeding creates inter- and intra-species synthetic yeast communities with enhanced bioproduction

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 16, 2024

Microorganisms can be engineered to sustainably produce a variety of products including fuels, pharmaceuticals, materials, and food. However, highly strains often result in low production yield, due undesired effects such as metabolic burden the toxicity intermediates. Drawing inspiration from natural ecosystems, construction synthetic community with division labor offer advantages for bioproduction. This approach involves dividing specific tasks among members, thereby enhancing functionality each member. In this study, we identify six pairs out fifteen composed auxotrophs Yarrowia lipolytica that spontaneously form robust syntrophic synergistic communities. We characterize stability growth dynamics these Furthermore, validate existence interactions between two yeast species, Y. Saccharomyces cerevisiae, find strain combination, Δtrp2 Δtrp4, forming stable species. Subsequently, introduce 3-hydroxypropionic acid (3-HP) biosynthesis pathway into by different strains. Our results demonstrate improved 3-HP both intra- interspecies communities compared monocultures. show formation communities, their potential improving bioproduction processes.

Язык: Английский

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Asymmetric Metabolic Adaptations Undermine Stability in Microbial Syntrophy

ISME Communications, Год журнала: 2025, Номер 5(1)

Опубликована: Янв. 1, 2025

Abstract Syntrophic interaction, driven by metabolite exchange, is widespread within microbial communities. However, co-inoculation of most auxotrophic microorganisms often fails to establish a stable exchange relationship. Here, we engineered two Escherichia coli strains, each dependent on the other for essential amino acid production, investigate dynamics syntrophic relationships. Through invasion-from-rare experiments, observed rapid formation consortia stabilized frequency-dependent selection, converging 2:1 ratio lysine-to-arginine auxotrophs. laboratory evolution over 25 days revealed that interactions were evolutionarily unstable, with cocultures collapsing as ΔL cells dominated population. Reduced fitness in was emergence “selfish” phenotype, characterized decreased arginine production and exploitation lysine produced ΔA cells. Dynamic metabolic assays utilization patterns strongly influenced strain. displayed plasticity, adjusting response availability, which enabled them outcompete In contrast, lacked similar resulting their negative selection. These findings demonstrate asymmetric responses selfish phenotypes destabilize Our work underscores importance balanced exchanges developing sustainable synthetic offers insights into evolutionary cooperation.

Язык: Английский

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