Podophyllotoxin (PTOX) is naturally produced by the plant Podophyllum species.Some of its derivatives are anticancer drugs, which are produced mainly by using chemical semi-synthesis methods.Recombinant bacteria have great potential in large-scale production of the derivatives of PTOX.
In addition to introducing the correct enzymes, the transportation of PTOX into the cells is an important L-Tyrosine factor, which limits its modification in the bacteria.Here, we improved the cellular uptake of PTOX into Escherichia coli with the help of the zero-valent sulfur transporter YedE1E2 in the presence of cetyltrimethylammonium bromide (CTAB).CTAB promoted the uptake of PTOX, but induced the production of reactive oxygen species.
A protein complex (YedE1E2) of YedE1 and YedE2 enabled E.coli Fruit cells to resist CTAB by reducing reactive oxygen species, and YedE1E2 was a hypothetical transporter.Further investigation showed that YedE1E2 facilitated the uptake of extracellular zero-valent sulfur across the cytoplasmic membrane and the formation of glutathione persulfide (GSSH) inside the cells.
The increased GSSH minimized oxidative stress.Our results indicate that YedE1E2 is a zero-valent sulfur transporter and it also facilitates CTAB-assisted uptake of PTOX by recombinant bacteria.