Advances in biosensors for microbial biosynthesis of amino acids and their derivatives

Amino acids and their derivatives play pivotal roles across diverse fields including biotechnology, pharmaceuticals, agriculture, and industrial manufacturing. The development of high-throughput screening methods for strains producing amino acids and their derivatives is crucial for both mining key enzymes and screening overproducers. This review systematically evaluates six classes of direct biosensors employed in the metabolic engineering of amino acid- or derivative-producing strains. These include biosensors based on transcription factors, riboswitches, Förster resonance energy transfer, circularly permuted fluorescent proteins, compound-inducible putative promoter regions, and protein translation elements. Their operational principles and recent advances in rational design, performance optimization, and practical implementation are critically analyzed. In addition, a systematic analysis of four categories of indirect biosensing strategies for the screening or regulation of amino acid- or derivative-producing strains is provided. These strategies target universal metabolic precursors, pathway-specific precursors, enzymatically transformed downstream metabolites, or competitive intermediates in branched pathways. Then, the design strategies, performance optimization methods, and practical implementation challenges of the existing biosensors are compared, which are accompanied by the discussion of the key parameters that are optimal for the biosensors applied in metabolic engineering. This work will facilitate the development of biosensors for metabolites that currently lack biosensing systems, and promote the innovation of the existing biosensors. These developments are expected to support efficient and sustainable production of amino acid-related compounds and other high-value metabolites.