Current Opinion in Systems Biology最新文献

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.

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.

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.

Chronotherapy aims at optimising the time of day and dosing of drugs administration. This is a promising perspective because the toxicity and efficacy of many drugs show a dependence on the time of the day at which they are administrated. Efficient cancer chronotherapy requires a good understanding of the interplay between the cell cycle and the circadian clock. Computational models offer a way to study the dynamics resulting from the coupling between these two biological oscillators and to predict successful therapeutic protocols. We review here recent advances and highlight key challenges for further developments of predictive mathematical models.

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.

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.

Most life forms harbor multiple, diverse mobile genetic elements (MGE) that widely differ in their rates and mechanisms of mobility. Recent findings on two classes of MGE in prokaryotes revealed a novel mechanism, RNA-guided transposition, where a transposon-encoded guide RNA directs the transposase to a unique site in the host genome. Tn7-like transposons, on multiple occasions, recruited CRISPR systems that lost the capacity to cleave target DNA and instead mediate RNA-guided transposition via CRISPR RNA. Conversely, the abundant transposon-associated, RNA-guided nucleases IscB and TnpB that appear to promote proliferation of IS200/IS605 and IS607 transposons were the likely evolutionary ancestors of type II and type V CRISPR systems, respectively. Thus, RNA-guided target recognition is a major biological phenomenon that connects MGE with host defense mechanisms. More RNA-guided defensive and MGE-associated functionalities are likely to be discovered.

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.

The growth of microbial populations in nature is dynamic, as the cellular physiology and environment of these populations change. Population dynamics have wide-ranging consequences for ecology and evolution, determining how species interact and which mutations fix. Understanding these dynamics is also critical for clinical and environmental applications in which we need to promote or inhibit microbial growth. We first address the latest efforts and outstanding challenges in measuring microbial population dynamics in natural environments. We next summarize fundamental concepts and empirical data on how population dynamics both shape and are shaped by evolutionary processes. Finally, we discuss the role of tradeoffs in microbial population dynamics, which may reveal physiological constraints and help to maintain ecological diversity. We find that current evidence for tradeoffs in population dynamics is limited, but that consideration of the evolutionary context of these tradeoffs is necessary for designing future experiments that can better address this problem.

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.