Senior Victorian minister Jaala Pulford, based in Ballarat, will not contest the next state election.
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Ms Pulford, an upper house member for Western Victoria, announced her resignation from politics on Friday after 16 years in parliament.
She currently holds the portfolios of employment, innovation, medical research, the digital economy, small business and resources where she will remain until the official end of the term.
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Previously, she was the first female agriculture minister.
In a statement, she said she has "given (her) all to public life".
"It is time for me to make way for the next generation and I cannot wait to see them thrive," Ms Pulford said.
She most recently announced $35 million of funding for children's cancer research, if the state government is reelected at the end of November.
It is an area of work close to Ms Pulford's heart, after losing her daughter to cancer in 2014 - she said she was particularly proud of her work supporting Ballarat Hospice workers.
"A fit for purpose workplace for the people who cared for my girl, is the best of them all," she said.
In her statement, Ms Pulford said it had been "the most rewarding journey in politics".
"I am conscious that I am making this decision on the eve of a state election but I am absolutely confident that the time is right for me, and for the Government," Ms Pulford said.
"While it is amazing to pass a law, design a program or fund a project, the best thing about being a politician is the people we meet."
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The state government will go into caretaker mode on Tuesday in the lead up to the election.
Mr Andrews said in a statement, Ms Pulford will continue to help with flood recovery efforts until a new government is formed.
Mr Andrews thanked Ms Pulford "for her many years of dedication to the people of Victoria".
Ms Pulford follows a number of senior ministers who will not be running for re-election including former deputy premier James Merlino, Lisa Neville, Martin Foley, and Martin Pakula, who announced their resignations in June.
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