title: Engineered Production of Tryprostatins inE. colithrough Reconstitution of a PartialftmBiosynthetic Gene Cluster fromAspergillussp.
abstract: Tryprostatin A and B are indole alkaloid-based fungal products that inhibit mammalian cell cycle at the G2/M phase. They are biosynthetic intermediates of fumitremorgins produced by a complex pathway involving a nonribosomal peptide synthetase (FtmA), a prenyltransferase (FtmB), a cytochrome P450 hydroxylase (FtmC), an O-methyltransferase (FtmD), and several additional enzymes. A partial fumitremorgin biosynthetic gene cluster (ftmABCD) fromAspergillussp. was reconstituted inEscherichia coliBL21(DE3) cells, with or without the co-expression of an Sfp-type phosphopantetheinyltransferase gene (Cv_sfp) fromChromobacterium violaceumNo. 968. Several recombinantE. colistrains produced tryprostatin B up to 106 mg/l or tryprostatin A up to 76 mg/l in the fermentation broth under aerobic condition, providing an effective way to prepare those pharmaceutically important natural products biologically.
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, PO Box 413, Milwaukee, Wisconsin 53201, USA.
authors.forename: Gopitkumar R
authors.initials: GR
authors.lastname: Shah
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, PO Box 413, Milwaukee, Wisconsin 53201, USA.
authors.forename: Shane R
authors.initials: SR
authors.lastname: Wesener
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, PO Box 413, Milwaukee, Wisconsin 53201, USA ; UNT System College of Pharmacy, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, Texas 76107, USA.
authors.forename: Yi-Qiang
authors.initials: YQ
authors.lastname: Cheng
keywords: ftm biosynthetic gene cluster; heterologous production; tryprostatins