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High-effective biosynthesis of baccatin Ⅲ by using the alternative acetyl substrate, N-acetyl-d-glucosamine.
Huang, J-J; Wei, T; Lin, J-F; Guo, L-Q; Han, W-F; Han, P-Y; Ye, A-Q.
Affiliation
  • Huang JJ; Department of Bioengineering, College of Food Science and Institute of Food Biotechnology, South China Agricultural University, Guangzhou, China.
  • Wei T; Research Center for Micro-Ecological Agent Engineering and Technology of Guangdong Province, Guangzhou, China.
  • Lin JF; Department of Bioengineering, College of Food Science and Institute of Food Biotechnology, South China Agricultural University, Guangzhou, China.
  • Guo LQ; Research Center for Micro-Ecological Agent Engineering and Technology of Guangdong Province, Guangzhou, China.
  • Han WF; Department of Bioengineering, College of Food Science and Institute of Food Biotechnology, South China Agricultural University, Guangzhou, China.
  • Han PY; Research Center for Micro-Ecological Agent Engineering and Technology of Guangdong Province, Guangzhou, China.
  • Ye AQ; Department of Bioengineering, College of Food Science and Institute of Food Biotechnology, South China Agricultural University, Guangzhou, China.
J Appl Microbiol ; 129(2): 345-355, 2020 Aug.
Article in En | MEDLINE | ID: mdl-32091657
AIMS: Paclitaxel is a type of broad-spectrum anticancer drug in short supply. The price of acetyl-CoA (17 709 677·4 USD mol-1 ), which is the acetyl group donor for the enzymatic synthesis of the intermediate, baccatin Ⅲ, is still the bottleneck of the mass production of paclitaxel. This study reports a novel acetyl group donor, which could substantially reduce the cost of production. METHODS AND RESULTS: In this study, a substrate spectrum with 14 kinds of representative acetyl-donor substitutes predicted by computer-aided methods was tested in a 10-deacetylbaccatin Ⅲ-10-O-acetyltransferase (DBAT) heterogeneous-expressed open-whole-cell catalytic system. The results of computer prediction and experimental analysis revealed the rule of the acetyl-donor compounds based on this substrate spectrum. N-acetyl-d-glucosamine (30·95 USD mol-1 , about 572 202-fold cheaper than acetyl-CoA) is selected as a suitable substitute under the rule. The yield when using N-acetyl-d-glucosamine as acetyl donor in open-whole-cell catalytic system was 2·13-fold of that when using acetyl-CoA. In the in vivo system, the yield increased 24·17%, which may indicate its cooperation with acetyl-CoA. CONCLUSION: The success of open-whole-cell synthesis and in vivo synthesis of baccatin Ⅲ by adding N-acetyl-d-glucosamine as acetyl substrate demonstrates that it is a useful substrate to improve the yield of baccatin Ⅲ. SIGNIFICANCE AND IMPACT OF THE STUDY: All these findings provided a potential acetyl-donor substitute for acetyl-CoA, as well as a low cost and efficient method of preparing paclitaxel through baccatin Ⅲ semi-synthesis.
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Full text: 1 Database: MEDLINE Main subject: Acetylglucosamine / Alkaloids Type of study: Prognostic_studies Language: En Journal: J Appl Microbiol Journal subject: MICROBIOLOGIA Year: 2020 Type: Article Affiliation country: China

Full text: 1 Database: MEDLINE Main subject: Acetylglucosamine / Alkaloids Type of study: Prognostic_studies Language: En Journal: J Appl Microbiol Journal subject: MICROBIOLOGIA Year: 2020 Type: Article Affiliation country: China