Current Opinion in Systems Biology最新文献

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.

Many proteins begin to fold as they are being synthesized by the ribosome. Growing experimental evidence, supported by new theory, simulation and bioinformatics studies, suggests that many proteins rely on co-translational folding in order to fold efficiently and to avoid misfolded intermediates that arise posttranslationally. Consistent with these findings, complementary bioinformatics analyses have revealed widespread evolutionary selection for efficient co-translational folding kinetics. This perspective summarizes recent theoretical and experimental advances that have uncovered specific molecular mechanisms underlying the benefits of co-translational folding in vivo. We highlight studies involving single-domain proteins that begin adopting nativelike structure on the ribosome, which can help commit misfolding-prone domains to their native state. We emphasize the need for new experimental techniques to probe the molecular details underlying this process systematically.

After decades of development, DNA synthesis, assembly, and sequencing technologies have reached a high level, allowing faster and cheaper acquirements of synthetic genes or even de novo synthesis of an entire genome. Meanwhile, the value of synthetic genomes keeps increasing, and the target organisms have covered viruses, bacteria, and yeast and moved toward higher eukaryotes. However, as the length of genomes moves from kilobase to gigabase, the cost of synthetic genome projects increases sharply and requires years of effort to complete. Therefore, new DNA synthesis technology and a next-generation DNA synthesizer are urgently needed. In this review, we focus mainly on the advances in DNA and genome synthesis and discuss difficulties that need to be addressed in both areas.

High-throughput (HT) methodologies are extensively applied in synthetic biology for the rapid enrichment and selection of desired properties from a wide range of genetic diversity. In order to effectively analyze these vast variants, HT tools must offer parallel experiments and compact reaction capabilities to enhance overall throughput. Here, we discuss about various aspects of three representative high-throughput screening (HTS) systems: microwell-, droplet-, and single-cell-based screening. These systems can be categorized based on their reaction volume, which in turn determines the associated technology, machinery, and supporting applications. Furthermore, HT techniques that rapidly connect numerous genotypes and phenotypes have evolved to enhance the precision of predictions through the integration of digital technologies like machine learning and artificial intelligence. The use of advanced HT techniques within biofoundry will enable rapid selection and analysis from extensive genetic diversity, making it a driving force for the advancement of synthetic biology.

Cell-free synthetic biology is swiftly progressing and is poised to revolutionize multiple domains within synthetic biology. By departing from the constraints of living cells, it dramatically expands potential applications, surmounting the intrinsic limitations associated with cellular systems, especially where access to cytosolic conditions poses challenges. The open nature of cell-free systems means their potential applications are vast, limited only by creative imagination. A burgeoning number of studies underline its versatility across a broad spectrum of fields. This review article offers an insight into the recent advancements in this vibrant area, pinpointing key achievements and challenges in arenas such as biomanufacturing, pathway prototyping, and material sciences.

Traditional therapeutics aim to diagnose, treat, and cure diseases through various synthetic and natural approaches. The emerging field of engineered living therapeutics (ELTs) genetically functionalizes living cells to alter the paradigm of designed solutions. In this review, we focus on ELTs derived from microbial cell scaffolds. We propose three synergistic modalities for the rational design of ELTs: first, use of regulatory operations to regulate genetic expression; second, integration of alternative biosensing inputs for directed application; third, choice of microbial chassis to deliver solutions. We highlight the challenges and future opportunities within each group and conclude by providing a prospective outlook for ELTs.

The development of synthetic biology has resulted in the use of genetically engineered microbes (GEMs), becoming increasingly critical for addressing global issues such as health, food shortage, climate crisis, and environmental pollution. However, GEMs also pose a potential threat to the ecosystem, necessitating the implementation of biocontainment strategies. Synthetic genetic circuits have the potential to provide an additional level of safety and control beyond traditional physical containment measures. The development of biocontainment strategies is ongoing, including the use of kill switches, auxotrophy, and stringent response circuits, to control the viability of GEMs. This review discusses the application and future directions of genetic circuits for microbial biocontainment strategies.

Anthropogenic carbon emissions are driving rapid changes to the earth's climate, disrupting whole ecosystems and endangering the stability of human society. Innovations in engineered microbial fermentation enable the fossil resource-free production of fuels, commodity chemicals, and materials, thereby reducing the carbon emissions associated with these products. Microorganisms have been engineered to catabolize sustainable sources of carbon and energy (i.e., plant biomass, plastic waste, and one-carbon feedstocks) and biosynthesize carbon-neutral or carbon-negative products. These engineering efforts exploit and optimize natural biological pathways or generate unnatural pathways which can biosynthesize chemicals that have not yet been accessed using synthetic chemistry. Recent advances in microbial fermentation seek not only to maximize the titer, rate, and yield of desired products, but also to tailor microbial catabolism to utilize inexpensive feedstocks. Ultimately, these advances aim to lower the cost of bioproduction so that microorganism-derived chemicals can be economically competitive with fossil-derived chemicals.

Microbial phototrophic communities dominated early Earth and thrive to this day, particularly in extreme environments. We focus on the impact of diel oscillations on phototrophic biofilms, especially in hot springs, where oxygenic phototrophs are keystone species that use light energy to fix carbon and often nitrogen. They exhibit photo-motility and stratification, and alter the physicochemical environment by driving O₂, CO_2, and pH oscillations. Omics analyses reveal extensive genomic and functional diversity in biofilms, but linking this to a predictive understanding of their structure and dynamics remains challenging. This can be addressed by better spatiotemporal resolution of microbial interactions, improved tools for building and manipulating synthetic communities, and integration of empirical and theoretical approaches.

Over the past two decades, genome sequencing has uncovered the diversity and distribution of insertion sequences within prokaryotic genomes. However, the complexity of insertion sequence ecology and evolution hinders us from understanding their nature. Recent studies have employed experimental and computational models to study insertion sequences, emphasizing their role in shaping prokaryotic genome structures. Nonetheless, related areas remain with limited understanding, such as the speciation of insertion sequences. We believe that future studies should continue to develop tractable experimental and computational models to advance our understanding of IS ecology and evolution and their influence on the evolution of prokaryotic genomes.