Studies on key steps controlling biosynthesis of antibiotics thiomarinol and mupirocin
作者： Ahmed Mohammed Omer-Bali
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摘要: The modular polyketide synthase responsible for biosynthesis of the antibiotic mupirocin occupies 75 kb Pseudomonas fluorescens NCIMB 10586, while a hybrid PKS/NRPS is thiomarinol located on 97 plasmid pTML1 in Pseudoalteromonas spp SANK 73390. Biosynthesis acyl side chains and are thought to be either through esterification fully synthesised fatty acid (C\(_9\) or C\(_8\)) extension PK derived ester starter unit which predicted carried out MmpB TmpB. mupU/O/V/C/F macpE proposed sufficient conversion pseudomonic B A. Mupirocin regulated via quorum sensing, regulation was not identified. Production determined occur after 8 hours growth, acidic conditions use acetone with ethyl acetate improved extraction. TmlU, amide ligase, did complement mupU mutant mupirocin, found block 9-hydroxynonanoic acid, causing truncation 9-HN. This suggests that MupU, prevents from being an iterative PKS. KS-B2/ACP-B2 shown involved removal C8-OH thiomarinol. Genetically manipulated increased production 3 4 fold without abolishing PA-B production. Fused mupU-macpE complemented NCIMB10586ΔmupUΔmacpE double mutant. However, insertion this fusion into blocked MmpA changed pathway. Attempts mobilise revealed RK2-R6K γ-ori integrated but recovery cointegrate has yet been recovered E. coli.
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