FRANKFURT, April 26 (Reuters) - Deutsche Bank is undertaking its biggest management shake-up since 2019, the German bank said on Wednesday as it announced the departure of Christiana Riley, who oversaw its U.S. operations.

Riley's exit to join Santander follows news last week that Deutsche's co-deputy chief executive Karl von Rohr was also leaving, and the restructuring marks the first major overhaul of the bank's board under Chairman Alex Wynaendts.

"It is time to focus the management board on the next phase of the bank's growth strategy, which is now more than ever about sustainable profitability, efficiency and effective controls," Wynaendts said.

Riley was one of two women on Deutsche's 10-member board, which will now only consist of only nine people - eight men and one woman - in what Deutsche said would be a "leaner" team.

Stefan Simon, who currently oversees legal and compliance, will take on the America's portfolio and relocate to New York.

Claudio de Sanctis, a Deutsche veteran who has overseen wealth management, will join the board to oversee the retail bank, Deutsche said.

And Chief Financial Officer James von Moltke will take on oversight of asset management, which includes its DWS fund management business. (Reporting by Tom Sims; Editing by Jane Merriman and Alexander Smith)