@article{mbs:/content/journal/micro/10.1099/mic.0.26015-0, author = "Hu, Zhihao and Pfeifer, Blaine A. and Chao, Elizabeth and Murli, Sumati and Kealey, Jim and Carney, John R. and Ashley, Gary and Khosla, Chaitan and Hutchinson, C. Richard", title = "A specific role of the Saccharopolyspora erythraea thioesterase II gene in the function of modular polyketide synthases", journal= "Microbiology", year = "2003", volume = "149", number = "8", pages = "2213-2225", doi = "https://doi.org/10.1099/mic.0.26015-0", url = "https://www.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.26015-0", publisher = "Microbiology Society", issn = "1465-2080", type = "Journal Article", keywords = "KS, ketosynthase", keywords = "Carb, carbenicillin", keywords = "Tet, tetracycline", keywords = "NRPS, non-ribosomal peptide synthetase", keywords = "Strep, streptomycin", keywords = "PKS, polyketide synthase", keywords = "6dEB, 6-deoxyerythronolide B", keywords = "ACP, acyl carrier protein", keywords = "DEBS, 6-deoxyerythronolide B synthase", keywords = "AT, acyltransferase", keywords = "TE, thiosesterase", abstract = "Bacterial modular polyketide synthase (PKS) genes are commonly associated with another gene that encodes a thioesterase II (TEII) believed to remove aberrantly loaded substrates from the PKS. Co-expression of the Saccharopolyspora erythraea ery-ORF5 TEII and eryA genes encoding 6-deoxyerythronolide B synthase (DEBS) in Streptomyces hosts eliminated or significantly lowered production of 8,8′-deoxyoleandolide [15-nor-6-deoxyerythronolide B (15-nor-6dEB)], which arises from an acetate instead of a propionate starter unit. Disruption of the TEII gene in an industrial Sac. erythraea strain caused a notable amount of 15-norerythromycins to be produced by utilization of an acetate instead of a propionate starter unit and also resulted in moderately lowered production of erythromycin compared with the amount produced by the parental strain. A similar behaviour of the TEII gene was observed in Escherichia coli strains that produce 6dEB and 15-methyl-6dEB. Direct biochemical analysis showed that the ery-ORF5 TEII enzyme favours hydrolysis of acetyl groups bound to the loading acyl carrier protein domain (ACPL) of DEBS. These results point to a clear role of the TEII enzyme, i.e. removal of a specific type of acyl group from the ACPL domain of the DEBS1 loading module.", }