Application of directed evolution and back-to-consensus algorithms to human alpha1-antitrypsin leads to diminished anti-protease activity and augmented anti-inflammatory activities

•Guided by directed evolution, point mutations were applied to human α1-antitrypsin.•Upon recombinant production (i) anti-protease attributes were lost.•Upon recombinant production (ii) anti-inflammatory attributes were augmented.•A novel functional anti-inflammatory domain was identified within α1-antitrypsin.•Directed evolution and α1-antitrypsin prove ‘The whole is greater than its parts’.