The heterologous expression of natural product biosynthetic gene clusters (BGCs) has traditionally been used as a genetic platform to link various natural product chemotypes to their corresponding genotypes. In recent years, heterologous expression has played an increasing role in natural products research with the advances in sequencing technologies and bioinformatics tools that allow for the rapid and systematic identification of known and cryptic BGCs from a large number of microbial genome sequences. The advances in synthetic biology have also facilitated the process of heterologous expression by providing tools for rapid cloning and engineering of BGCs to improve production yield or to activate silent BGCs. This paper summarizes the recent progress in the cloning and engineering of natural product BGCs and highlights recent examples of the heterologous expression of both known and cryptic BGCs in Streptomyces hosts, which will continue to play a pivotal role in genomics-driven natural product research.
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http://dx.doi.org/10.1016/j.copbio.2020.12.016 | DOI Listing |
Elife
January 2025
Department of Neurology, Baylor College of Medicine, Houston, United States.
variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path.
View Article and Find Full Text PDFJ Membr Biol
January 2025
Departamento de Alimentos. División de Ciencias de la Vida, Campus Irapuato-Salamanca, Universidad de Guanajuato, Carretera Irapuato Silao km 9, 36500, Irapuato, Guanajuato, México.
The Cell-Free Protein Synthesis (CFPS) is an innovative technique used to produce various proteins. It has several advantages, including short expression times, no strain engineering is required, and toxic proteins such as membrane proteins can be produced. However, the most important advantage is that it eliminates the need for a living cell as a production system.
View Article and Find Full Text PDFiScience
December 2024
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0435, USA.
Cytomegalovirus is a promising vaccine vector; however, mechanisms promoting CD4 T cell responses to challenge, by CMV as a vector, are unknown. The ability of MCMV to prolong immunity generated by short-lived malaria vaccine was tested. MCMV provided non-specific protection to challenge with and increased interleukin-12 (IL-12) and CD8α dendritic cell (DC) numbers through prolonged MCMV-dependent interferon gamma (IFN-γ) production.
View Article and Find Full Text PDFAppl Biochem Biotechnol
January 2025
College of Food Science and Light Industry, Nanjing Tech University, Nanjing, 211816, China.
Carrageenan has strong structural heterogeneity, resulting in the production of several hybridized forms in nature. Furcellaran is a typical hybrid type of carrageenan that includes both κ-carrageenan and β-carrageenan motifs in its structure. The discovery and characterization of a novel furcellaranase is of great significance for investigating and determining the structures of carrageenan.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Chemical Engineering, Imperial College London, London, UK.
Degradation tags, otherwise known as degrons, are portable sequences that can be used to alter protein stability. Here, we report that degron-tagged proteins compete for cellular degradation resources in engineered mammalian cells leading to coupling of the degradation rates of otherwise independently expressed proteins when constitutively targeted human degrons are adopted. We show the effect of this competition to be dependent on the context of the degrons.
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