The biotechnological production of amino acids occurs at the million-ton scale and annually about 6 million tons of L-glutamate and L-lysine are produced by Escherichia coli and Corynebacterium glutamicum strains. L-glutamate and L-lysine production from starch hydrolysates and molasses is very efficient and access to alternative carbon sources and new products has been enabled by metabolic engineering. This review focusses on genetic and metabolic engineering of amino acid producing strains. In particular, rational approaches involving modulation of transcriptional regulators, regulons, and attenuators will be discussed. To address current limitations of metabolic engineering, this article gives insights on recent systems metabolic engineering approaches based on functional tools and method such as genome reduction, amino acid sensors based on transcriptional regulators and riboswitches, CRISPR interference, small regulatory RNAs, DNA scaffolding, and optogenetic control, and discusses future prospects. (C) 2017 Elsevier Ltd. All rights reserved.