Characterization of a methyltransferase involved in herboxidiene biosynthesis |
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Authors: | Dayu Yu Fuchao Xu Shuwei Zhang Lei Shao Siyuan Wang Jixun Zhan |
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Affiliation: | 1. Department of Applied Chemistry and Biological Engineering, College of Chemical Engineering, Northeast Dianli University, Jilin, Jilin 132012, China;2. Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322, United States |
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Abstract: | The herboxidiene biosynthetic gene cluster contains a regulatory gene and six biosynthetic genes that encode three polyketide synthases (HerB, HerC and HerD) and three tailoring enzymes (HerE, HerF and HerG). Through single crossover recombination, an integrative plasmid was inserted into the genome of Streptomyces chromofuscus ATCC 49982 between herE and herF, resulting in low-level expression of herF and the downstream herG. The mutant strain produced two new compounds, 18-deoxy-25-demethyl-herboxidiene and 25-demethyl-herboxidiene. HerF was expressed in Escherichia coli and biochemically characterized as the dedicated methyltransferase in herboxidiene biosynthesis. It prefers 25-demethyl-herboxidiene to 18-deoxy-25-demethyl-herboxidiene, suggesting that C-25 methylation is the last tailoring step. |
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Keywords: | Herboxidiene Anti-cholesterol Polyketide biosynthesis Methyltransferase Tailoring reaction |
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