Hemoglobin-catalyzed synthesis of indolizines via a multicomponent reaction has been reported for the first time. The corresponding indolizines were obtained in moderate to high yields by using this method. This mild, efficient and practical method is distinguished by the use of a commercially inex-Indolizines, a class of heteroaromatic compounds containing two condensed rings (5-and 6-membered) and a bridging nitrogen atom, have been widely applied in natural products and synthetic pharmaceuticals. [1,2] These types of compounds have also been applied as dyes and biological markers due to their photophysical properties. [3][4][5][6][7] Therefore, the development of efficient methods for the synthesis of indolizines continues to attract the attention of organic chemists. Traditional synthetic routes to indolizines mainly comprise the Scholtz or Chichibabin reactions. More recently, cycloaddition reactions (1,3-dipolar cycloadditions), intramolecular cyclizations using acetic anhydride, formation of C3-C4 bond, formation of C1-C9 bond, and formation of C8-C9 bond have been reported. [8][9][10][11][12][13][14] However, most of these methods suffer from some drawbacks, such as the formation of conjugate-acid waste, narrow substrate scope, harsh reaction conditions, need for toxic transition-metal catalysts and harmful organic solvents. Thus, an environmentally preferable and efficient method to synthesize indolizines for practical applications must be developed.Biocatalysis is a highly attractive strategy in organic synthesis for organic synthesis due to its efficient, selective and environment-friendly characteristics. [15] A new biocatalytic approach relies on the promiscuity of enzymes to catalyze reactions that are different than their native functions. This interesting property of protein allows chemists to explore new types of biocatalytic organic reactions and dramatically expands the application of catalytic proteins within the field of organic chemistry. [16][17][18][19][20][21][22] [a]