1887

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 TEII and genes encoding 6-deoxyerythronolide B synthase (DEBS) in 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 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 strains that produce 6dEB and 15-methyl-6dEB. Direct biochemical analysis showed that the TEII enzyme favours hydrolysis of acetyl groups bound to the loading acyl carrier protein domain (ACP) 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 ACP domain of the DEBS1 loading module.

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2003-08-01
2019-11-19
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