Applied Microbiology and Biotechnology, Vol.97, No.9, 3763-3772, 2013
Lysine biosynthesis in microbes: relevance as drug target and prospects for beta-lactam antibiotics production
Plants as well as pro- and eukaryotic microorganisms are able to synthesise lysine via de novo synthesis. While plants and bacteria, with some exceptions, rely on variations of the meso-diaminopimelate pathway for lysine biosynthesis, fungi exclusively use the alpha-aminoadipate pathway. Although bacteria and fungi are, in principle, both suitable as lysine producers, current industrial fermentations rely on the use of bacteria. In contrast, fungi are important producers of beta-lactam antibiotics such as penicillins or cephalosporins. The synthesis of these antibiotics strictly depends on alpha-aminoadipate deriving from lysine biosynthesis. Interestingly, despite the resulting industrial importance of the fungal alpha-aminoadipate pathway, biochemical reactions leading to alpha-aminoadipate formation have only been studied on a limited number of fungal species. In this respect, just recently an essential isomerisation reaction required for the formation of alpha-aminoadipate has been elucidated in detail. This review summarises biochemical pathways leading to lysine production, discusses the suitability of interrupting lysine biosynthesis as target for new antibacterial and antifungal compounds and emphasises on biochemical reactions involved in the formation of alpha-aminoadipate in fungi as an essential intermediate for both, lysine and beta-lactam antibiotics production.