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The TOL network of P seudomonas putida mt‐2 processes multiple environmental inputs into a narrow response space
Author(s) -
SilvaRocha Rafael,
Lorenzo Víctor
Publication year - 2013
Publication title -
environmental microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.954
H-Index - 188
eISSN - 1462-2920
pISSN - 1462-2912
DOI - 10.1111/1462-2920.12014
Subject(s) - biology , pseudomonas putida , gene regulatory network , computational biology , gene , set (abstract data type) , operon , metabolic pathway , in silico , synthetic biology , biological system , genetics , computer science , gene expression , escherichia coli , programming language
Summary The TOL system encoded by plasmid pWW0 of P seudomonas putida mt‐2 is able to sense a large number of both exogenous and endogenous signals as inputs for the genetic and metabolic circuit that determines the biodegradation of m‐ xylene. However, whether the enormous combinatorial space of inputs is translated into an equally variable response landscape or is processed into very few outcomes remains unclear. To address this question, we set out to define the number of states that can be obtained by a network of a given set of genes under the control of a specified regulatory circuit that is exposed to all possible combinations of inputs. To this end, the TOL network and its regulatory wiring were formalized as a synchronous logic B oolean circuit that had 10 signals (i.e. pathway substrates, temperature, sugars, amino acids, metabolic regimes and global regulators) as possible inputs. The analysis of the attractors of the circuit using a satisfiability ( SAT ) algorithm revealed that only eight transcriptional states are reached in response to the 1024 possible combinations of stimuli. The experimental validation resulted in a refinement of the model through the addition of a previously unknown interaction that controls the meta catabolic pathway. The full induction of the two xyl operons occurred with only 1.6% of the input combinations, which suggests that the architecture of the network allows the expression of the xyl genes only under a very narrow range of conditions. These data not only explain much of the unusual layout of the TOL circuit but also strengthen the view of the regulatory circuits of environmental bacteria as digital decision‐making devices.