title: Development of a Transcription Factor-Based Lactam Biosensor.
abstract: Lactams are an important class of commodity chemicals used in the manufacture of nylons, with millions of tons produced every year. Biological production of lactams could be greatly improved by high-throughput sensors for lactam biosynthesis. To identify biosensors of lactams, we applied a chemoinformatic approach inspired by small molecule drug discovery. We define this approach as analogue generation toward catabolizable chemicals or AGTC. We discovered a lactam biosensor based on the ChnR/Pb transcription factor-promoter pair. The microbial biosensor is capable of sensing ε-caprolactam, δ-valerolactam, and butyrolactam in a dose-dependent manner. The biosensor has sufficient specificity to discriminate against lactam biosynthetic intermediates and therefore could potentially be applied for high-throughput metabolic engineering for industrially important high titer lactam biosynthesis.
authors.affiliation: Joint BioEnergy Institute , Emeryville, California United States.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Joint BioEnergy Institute , Emeryville, California United States.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Barajas
authors.affiliation: Joint BioEnergy Institute , Emeryville, California United States.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Burdu
authors.affiliation: Joint BioEnergy Institute , Emeryville, California United States.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ruegg
authors.affiliation: Joint BioEnergy Institute , Emeryville, California United States.
authors.forename: Bryton
authors.initials: B
authors.lastname: Dias
authors.affiliation: Joint BioEnergy Institute , Emeryville, California United States.|Biological Systems & Engineering Division, Lawrence Berkeley National Laboratory , Berkeley, California United States.|The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark , Lyngby, Denmark.
authors.forename: Jay D
authors.identifier: 0000-0002-4910-2222
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000378:metabolism; D015374:Biosensing Techniques / Q000379:methods; D002209:Caprolactam / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D007769:Lactams / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics; D054852:Small Molecule Libraries / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D007769:Lactams; D054852:Small Molecule Libraries; D014157:Transcription Factors; C511520:valerolactam; D002209:Caprolactam