Tryptophan Metabolites: A Microbial Perspective

Abstract

The discovery of the regulation of tryptophan biosynthetic pathway by means of a repressible operon has been recognised as a milestone in genetics. This long multistep pathway is energetically so expensive that numerous allosteric control loops exist in addition to tight genetic regulation. That’s why essential amino acid tryptophan is a valuable product for food industry and animal breeding. Traditionally, vitamin auxotrophs of soil microorganisms have been used for amino acid manufacturing. However, in the age of synthetic biology, metabolic engineering has recently become the method of choice to construct the producer strains. Additionally, in contrast to mammalian cells, bacterial cells are able to produce tryptophan starting at central metabolic intermediates from pentose phosphate pathway and glycolysis. This metabolic divergence provides an excellent target for the development of novel antimicrobials which interfere with the biosynthesis of tryptophan. Tryptophan metabolism makes at least two contributions to microbial quorum-sensing pathways, which may have implications in antimicrobial chemotherapy. The autoinducers of renowned Pseudomonas quinolone signalling system originate either from kynurenine or shikimate pathways. Fluorinated 4-quinolone derivative antimicrobial drugs exhibit antipathogenic effects at subinhibitory concentration, presumably by interfering with Pseudomonas quinolone signalling. Another recently recognised bacterial signal molecule is indole, a degradation product of tryptophan. Unconventional stationary phase signal molecule indole is unique, as no receptor/response regulator protein has been identified to date. Instead, the effects of indole have been attributed to its physicochemical interaction with the cell membrane.