A new post-PKS modification process in the carbamoyltransferase gene inactivation strain of Streptomyces hygroscopicus 17997

作者：Li, Yonghai^*; He, Weiqing; Wang, Yucheng; Wang, Yiguang; Shao, Rongguang

来源：Journal of Antibiotics, 2008, 61(6): 347-355.

DOI：10.1038/ja.2008.49

• geldanamycin
• carbamoyltransferase gene
• gene inactivation
• post-polyketide synthase modification
• geldanamycin analogues

Genetic manipulation of geldanamycin (GDM) producer Streptomyces species is a rational approach to understand biosynthesis processes and create new analogues. In this study, the carbamoyltransferase gene gdmN was inactivated by insertion of an apramycin-resistance gene aac3 (IV) into the genome of the geldanamycin-producing strain Streptomyces hygroscopicus 17997. GDM analogues produced by this mutant strain were isolated and characterized, such as new compound 4,5-dihydro-7-O-desearbamoyl-7-hydroxy- 19-O-glycylgeldanamycin. This compound could be converted to compound 4,5-dihydro-19-O-glycylgeldanamycin, another new GDM analogue, by a strain of Streptomyces hygroscopicus 17997 in which the GDM-pks was inactivated. These new compounds exhibited reductions of cytotoxicity against HepG2 cancer cells, but increases of aqueous solubility. These results suggest that a new post-polyketide synthase modification was involved in this process to produce new GDM analogues.

• 出版日期2008-6
• 单位中国医学科学院医药生物技术研究所