Modeling the architecture of the regulatory system controlling methylenomycin production in Streptomyces coelicolor

摘要: The antibiotic methylenomycin A is produced naturally by Streptomyces coelicolor A3(2), a model organism for streptomycetes. This compound of particular interest to synthetic biologists because all the associated biosynthetic, regulatory and resistance genes are located on single cluster SCP1 plasmid, making entire module easily transferable between different bacterial strains. Understanding further regulation biosynthesis producing gene could assist in identification motifs that can be exploited systems rational engineering novel natural products antibiotics. We identify validate plausible architecture system controlling production S. using mathematical modeling approaches. Model selection via an approximate Bayesian computation (ABC) approach identifies three candidate architectures most likely produce available experimental data, from set 48 possible candidates. Subsequent global optimization parameters these accurately reproduces dynamical response system, as captured time series data production. Further analyses variants this capture effects knockouts also reproduce qualitative results observed mutant mechanistic developed study recapitulates current biological knowledge cluster, used future studies make testable predictions formulate experiments improve our understanding complex system.