Biomanufacturing, driven by technologies such as synthetic biology, offers significant potential to advance the bioeconomy and promote sustainable development. It is anticipated to transform traditional manufacturing and become a key industry in future strategies. Cell factories are the core of biomanufacturing. The advancement of synthetic biology and growing market demand have led to the production of a greater variety of natural products and increasingly complex metabolic pathways. However, this progress also presents challenges, notably the conflict between natural product production and chassis cell growth. This conflict results in low productivity and yield, adverse side effects, metabolic imbalances, and growth retardation. Enzyme co-localization strategies have emerged as a promising solution. This article reviews recent progress and applications of these strategies in constructing cell factories for efficient natural product production. It comprehensively describes the applications of enzyme-based compartmentalization, metabolic pathway-based compartmentalization, and synthetic organelle-based compartmentalization in improving product titers. The article also explores future research directions and the prospects of combining multiple strategies with advanced technologies.
L-Phenylalanine (L-Phe) is an important aromatic amino acid, which has been widely used in food, health care products, medicine and other fields. Based on the relatively mature microbial biosynthesis process, a variety of L-phenylalanine-derived compounds have attracted more and more attentions owing to their extensively potential applications in the fields of food, medicine, spices, cosmetics, and pesticides. However, the challenge of biosynthesis of L-phenylalanine-derived compounds remains the issue of low production and productivity. With the development of metabolic engineering and synthetic biology, the biosynthesis of L-phenylalanine has reached a high level. Therefore, the synthesis of L-phenylalanine-derived compounds based on high production strains of L-phenylalanine has broad prospects. In addition, some L-phenylalanine-derived compounds are more suitable for efficient synthesis by exogenous addition of precursors due to their longer metabolic pathways and the inhibitory effects of many intermediate products. This review systematically summarized the research progress of L-phenylalanine-derived compounds, including phenylpyruvate derivatives, trans-cinnamic derivatives, p-coumaric acid derivatives and other L-phenylalanine-derived compounds (such as flavonoids). Finally, the main strategies to improve the production of L-phenylalanine-derived compounds were summarized, and the development trends of the synthesis of L-phenylalanine-derived compounds by microbial method were also prospected.
Notable advancements in single-cell omics technologies have not only addressed longstanding challenges but also enabled unprecedented studies of cellular heterogeneity with unprecedented resolution and scale. These strides have led to groundbreaking insights into complex biological systems, paving the way for a more profound comprehension of human biology and diseases. The droplet microfluidic technology has become a crucial component in many single-cell sequencing workflows in terms of throughput, cost-effectiveness, and automation. Utilizing a microfluidic chip to encapsulate and profile individual cells within droplets has significantly improved single-cell research. Therefore, this review aims to comprehensively elaborate the droplet microfluidics-assisted omics methods from a single-cell perspective. The strategies for using droplet microfluidics in the realms of genomics, epigenomics, transcriptomics, and proteomics analyses are first introduced. On this basis, the focus then turns to the latest applications of this technology in different sequencing patterns, including mono- and multi-omics. Finally, the challenges and further perspectives of droplet-based single-cell sequencing in both foundational research and commercial applications are discussed.
Biomolecular condensates are intriguing entities found within living cells. These structures possess the ability to selectively concentrate specific components through phase separation, thereby playing a crucial role in the spatiotemporal regulation of a wide range of cellular processes and metabolic activities. To date, extensive studies have been dedicated to unraveling the intricate connections between molecular features, physical properties, and cellular functions of condensates. This collective effort has paved the way for deliberate engineering of tailor-made condensates with specific applications. In this review, we comprehensively examine the underpinnings governing condensate formation. Next, we summarize the material states of condensates and delve into the design of synthetic intrinsically disordered proteins with tunable phase behaviors and physical properties. Subsequently, we review the diverse biological functions demonstrated by synthetic biomolecular condensates, encompassing gene regulation, cellular behaviors, modulation of biochemical reactions, and manipulation of endogenous protein activities. Lastly, we discuss future challenges and opportunities in constructing synthetic condensates with tunable physical properties and customized cellular functions, which may shed light on the development of new types of sophisticated condensate systems with distinct functions applicable to various scenarios.
This review examines a wide range of marine microbial-derived bioactive peptide molecules, emphasizing the significance of reverse engineering in their production. The discussion encompasses the advancements in Marine Natural Products (MNPs) bio-manufacturing through the integration of omics-driven microbial engineering and bioinformatics. The distinctive features of non-ribosomally synthesised peptides (NRPs), and ribosomally synthesised precursor peptides (RiPP) biosynthesis is elucidated and presented. Additionally, the article delves into the origins of common peptide modifications. It highlights various genome mining approaches for the targeted identification of Biosynthetic Gene Clusters (BGCs) and novel RiPP and NRPs-derived peptides. The review aims to demonstrate the advancements, prospects, and obstacles in engineering both RiPP and NRP biosynthetic pathways.
The burgeoning field of bioinformatics has seen a surge in computational tools tailored for omics data analysis driven by the heterogeneous and high-dimensional nature of omics data. In biomedical and plant science research multi-omics data has become pivotal for predictive analytics in the era of big data necessitating sophisticated computational methodologies. This review explores a diverse array of computational approaches which play crucial role in processing, normalizing, integrating, and analyzing omics data. Notable methods such similarity-based methods, network-based approaches, correlation-based methods, Bayesian methods, fusion-based methods and multivariate techniques among others are discussed in detail, each offering unique functionalities to address the complexities of multi-omics data. Furthermore, this review underscores the significance of computational tools in advancing our understanding of data and their transformative impact on research.