Current Opinion in Systems Biology最新文献

Concerns about environmental issues and limited fossil resources have increased interest and efforts in developing sustainable production of bio-based chemicals and fuels using microorganisms. Advanced metabolic engineering has developed microbial cell factories (MCFs) with the support of synthetic biology and systems biology. Isoprenoids are one of the largest classes of natural products and possess many practical industrial applications. However, it is challenging to meet the market demand for isoprenoids because of the current inefficient and unsustainable strategies for isoprenoid production such as chemical synthesis and plant extraction. Therefore, many efforts have been made to build isoprenoid-producing MCFs by applying metabolic engineering strategies, biological devices, and machinery from synthetic biology and systems biology. This review introduces recent studies of strain engineering and applications of biological tools and systems for developing isoprenoid MCFs. In addition, we also reviewed the isoprenoid fermentation strategies that lead to the best performance of isoprenoid-producing MCFs.

How does genetic sequence give rise to biological function? Answering this question is key to our understanding of life and the construction of synthetic biosystems that fight disease, resource scarcity and climate change. Unfortunately, the virtually infinite number of possible sequences and limitations in their functional characterization limit our current understanding of sequence-function relationships. To overcome this dilemma, several high-throughput methods to experimentally link sequences to corresponding functional properties have been developed recently. While all of these share the goal to collect sequence-function data at large scale, they differ significantly in their technical approach, functional readout and application scope. Herein, we highlight recent developments in the aspiring field of high-throughput sequence-function mapping providing a critical assessment of their potential in synthetic biology.

Gas fermentation using autotrophic acetogenic bacteria has been industrialized, however, its full potential remains untapped, with only native products like ethanol being produced thus far. Advancements in synthetic biology have enabled the recombinant production of diverse biocommodities to broaden their limited natural product spectrum from C1-gases. Additionally, co-culturing acetogens with other microorganisms holds the potential for expanding the product spectrum further. However, commercialization remains challenging due to complex pathway and (co)culturing optimizations. To address this, novel synthetic biology tools, including the use of high throughput biopart screenings using reporter proteins, the deployment of cell-free systems to combine best-performing enzymes, and the identification and elimination of competing pathways, can be employed. Incorporating genetically engineered strains in co-cultures improves dependencies, directs product formation, and increases resilience, enhancing bioproduction efficiency. This review emphasizes using these tools to enhance the recombinant production of biocommodities, offering promising solutions to overcome existing challenges.

Integration of cell-free systems with genetic biosensors is emerging as an advantageous platform for small molecule detection. This biosensor-coupled cell-free system simplifies an assay-and-detection procedure by combining the advantages of rapid and efficient protein expression through a cell-free system and the in situ detection capabilities provided by genetic biosensors. Moreover, this system is easy to assay multiple conditions at once, as the open environment of the cell-free systems enhances overall ease of handling. In this review, we focus on the acceleration of enzyme and pathway prototyping using cell-free biosensors, as well as strategies to improve the sensitivity and specificity of biosensors. High-throughput screening tools that can expand the prototyping process by generating massive data sets for rapid evaluation were also described.

Synthetic biology has promoted a conceptual shift in metabolic engineering for the microbial production of industrial chemicals toward a sustainable economy. Engineering principles from synthetic biology and metabolic engineering are integrated to redesign cellular metabolism to create microbial cell factories with emerging and programmable functionalities. Combining metabolic engineering with programmed spatial control is a promising approach that enables deep rewiring of microbial cell factory metabolism for the efficient production of bio-based chemicals. In this review, we discuss metabolic compartmentalization approaches for programmable control of cellular metabolism, including intracellular or intercellular partitioning-based organization of biosynthetic pathways. We also examine the designs and applications of cellular compartments and their analogs, highlighting selected examples for creating efficient and sustainable microbial cell factories.

A germline-soma distinction — irreversible differentiation from reproductive germline cells to sterile somatic cells — is a landmark of cellular cooperation in metazoans. Traditionally, this distinction was considered a property of only some metazoan taxa, such as vertebrates and insects. However, recent studies on a number of other metazoan taxa are challenging this traditional perspective, suggesting that a germline-soma distinction is widespread among metazoans. Here, we review recent molecular and cellular evidence supporting this suggestion and emphasise the difference between germline-soma distinction and germline segregation. We also outline the considerable diversity among metazoans in germline specification, segregation and regeneration. We finish by discussing how evolutionary explanations for this diversity can be investigated by harnessing theoretical modelling approaches.

In recent years, synthetic biology has provided many engineering approaches to reprogram and engineer cells in diverse applications including the development of novel therapeutics. Engineered cells provide advantages over small molecules or biologics, as these cells can be reprogrammed to have spatial and temporal control over the delivery of therapeutics in response to disease biomarkers. Herein, some of the recent applications of engineered live bacterial therapeutics against human diseases such as cancer, metabolic disorders, gastrointestinal diseases, and infections are reviewed. Furthermore, this review highlights active clinical trials on engineered cells with promising results.

To achieve a circular bioeconomy, carbon streams can be utilised through microbial conversion to produce value-added compounds. Although some microorganisms are naturally able to grow on these renewable carbon sources and generate desirable molecules, significant engineering is required to develop platform chassis exhibiting attractive performance parameters for industrial-scale processes. Here, we provide a brief overview of the core considerations in chassis engineering for autotrophic bioproduction, including carbon and energy supply, in addition to emerging standards for rewiring metabolic pathways to enhance growth and biosynthetic capabilities. We highlight examples of successful strategies, placing emphasis on recent advances in engineering autotrophic capabilities in both native autotrophs and heterotrophs.

The increased awareness of the pharmaceutical supply chain issues after the recent pandemic crisis has emphasized the need for innovative drug discovery. Natural products (NPs) have emerged as promising candidates to address pandemics due to their diverse structures and medicinal properties. However, development of novel NP-drugs in pharmaceutical supply chains has faced many challenges, including the absence of an efficient large-scale production platform to meet market demands. The advent of systems metabolic engineering has facilitated the efficient production of NPs in microorganisms compared with traditional plant-based and chemical-based production. In this article, we review recent strategies in systems metabolic engineering that have opened up new avenues for NP-drug discovery and production. In addition, we suggest viewpoints on how combinatorial approaches of systems metabolic engineering and synthetic chemistry will further enhance the diversity of NP-drugs and provide prospects for the development of NP-drugs in the pharmaceutical supply chain.