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                                    SECTION II. APPLIED BIOTECHNOLOGY IN THE PHARMACEUTICAL INDUSTRY... 335And codon 88 (AAG) encoding for lysine in the wild-type strain was replaced by codon 88 (AGG) encoding for arginine in the A. hibisca M14 strain.Table 2. The pradimicin A production of A. hibisca wild-type and mutant strainsStrains Mutation Pradimicin yield (mg/L)A. hibisca M4 K43M 52.4%u00b10.4A. hibisca M14 K88R 48.6%u00b10.64. DISCUSSIONRibosome engineering is a simple, efficient and time-saving strategy to enhace and activate the production of natural products in Actinomycetes. In this study, ribosome engineering was applied to enhance the production of pradimicin. The pradimicin production of A. hibisca M4 is 52.4%u00b10.4 mg/L, which is 6.1-fold higher than that of A. hibisca P172-2 (8.6%u00b10.2 mg/L).. In previous studies, Paudel et al. expressed regulator genes in A. hibisca P157-2. It led to increase in the production of pradimicin A by 5.38 fold [5]. After that, two ABC transporter genes: pdmR1 and pdmR2 were overexpressed in A. hibisca P157-2. The result was that pradimicin A production was increased by 5.4-fold compared to that of the wild-type strain [6]. A. hibisca M4 strain produced higher levels of pradimicin than the strains created by Paudel. It is shown that ribosome engineering is a highly efficient method compared to other methods in enhancing the production of pradimicin. In further studies in enhancing the yield of pradimicin, we can consider combining ribosome engineering methods with metabolic engineering (expression regulatory gene and overexpression transporter gene). This combination will promise to get positive results in creating industrial strain 
                                
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