title: The polyketide backbone of thiolactomycin is assembled by an unusual iterative polyketide synthase.
abstract: Following the in vivo investigation of thiotetronate assembly in Lentzea sp. and in S. thiolactonus NRRL 15439 (Havemann et al., Chem. Commun., 2017, DOI: 10.1039/c6cc09933e), the minimal set of genes required for thiolactomycin production was determined through heterologous expression and the mechanism for polyketide assembly was established in vitro through incubation of recombinant TlmB with its substrates in the presence of either nonhydrolysable or hydrolysable chemical probes. The results presented here constitute unequivocal evidence of enzymatic processing by an unusual iterative polyketide synthase.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. pfl10@cam.ac.uk.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Yurkovich
authors.affiliation: Department of Chemistry, University of Warwick, Library Road, CV4 7AL, UK. M.Tosin@warwick.ac.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Jenkins
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, People's Republic of China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Chemistry, University of Warwick, Library Road, CV4 7AL, UK. M.Tosin@warwick.ac.uk.
authors.forename: Manuela
authors.identifier: http://orcid.org/0000-0003-4340-9431
authors.initials: M
authors.lastname: Tosin
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. pfl10@cam.ac.uk.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Leadlay
mesh_terms: D000192:Actinomycetales / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000378:metabolism*; D053898:Biosynthetic Pathways; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013876:Thiophenes / Q000032:analysis / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D013876:Thiophenes; D048630:Polyketide Synthases; C035068:thiolactomycin