Customized molecular tools to strengthen metabolic engineering of cyanobacteria

Abstract

Cyanobacteria are promising oxygenic phototrophs for the production of various compounds. For their (photo)biotechnological exploitation, molecular tools are required, such as, for the introduction and expression of heterologous genes, or the modulation of enzyme activities or entire pathways. Concepts and strategies for the development of photosynthetic biomanufacturing technologies based on cyanobacteria have been extensively reviewed, as well as certain specialized aspects of their genetic manipulation. However, options for metabolic engineering of specific cyanobacterial cells are still less developed than those for other bacteria of biotechnological relevance. In addition to the standard genetic toolbox for “classical” metabolic engineering, we emphasize certain aspects, including recently developed vector systems for the extrachromosomal maintenance of genes and approaches based on clustered regularly interspaced short palindromic repeats (CRISPR) interference. We highlight the development of custom molecular tools for specific strains or products, discuss the emerging use of small regulatory proteins that appear promising for advanced metabolic engineering approaches to promote specific product formation, and provide an overview of suitable online resources. Furthermore, we discuss the current trends in this field and indicate their potential, such as using suitable product sensors that enable systematic screening, and optimization approaches.