title: Applications of genome editing by programmable nucleases to the metabolic engineering of secondary metabolites.
abstract: Genome engineering is a branch of modern biotechnology composed of a cohort of protocols designed to construct and modify a genotype with the main objective of giving rise to a desired phenotype. Conceptually, genome engineering is based on the so called genome editing technologies, a group of genetic techniques that allow either to delete or to insert genetic information in a particular genomic locus. Ten years ago, genome editing tools were limited to virus-driven integration and homologous DNA recombination. However, nowadays the uprising of programmable nucleases is rapidly changing this paradigm. There are two main families of modern tools for genome editing depending on the molecule that controls the specificity of the system and drives the editor machinery to its place of action. Enzymes such as Zn-finger and TALEN nucleases are protein-driven genome editors; while CRISPR system is a nucleic acid-guided editing system. Genome editing techniques are still not widely applied for the design of new compounds with pharmacological activity, but they are starting to be considered as promising tools for rational genome manipulation in biotechnology applications. In this review we will discuss the potential applications of programmable nucleases for the metabolic engineering of secondary metabolites with biological activity.
authors.affiliation: Departamento de Ciências e Tecnologia da Biomassa, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, Campus de Caparica, 2829-516 Caparica, Portugal; MEtRICs, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, Campus de Caparica, 2829-516 Caparica, Portugal. Electronic address: aldl@fct.unl.pt.
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Leitão
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Costa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal. Electronic address: fenguita@fm.ul.pt.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Enguita
mesh_terms: D064113:CRISPR-Cas Systems; D000072669:Gene Editing; D023281:Genomics; D060847:Metabolic Engineering; D000069896:Transcription Activator-Like Effector Nucleases
chemical_list: D000069896:Transcription Activator-Like Effector Nucleases
keywords: CRISPR-Cas9; Epigenome editing; Genome editing; Hybrid metabolites; Secondary metabolism; TALEN