The invention relates to the technical field of synthetic biology and microbial fermentation, in particular to modification of deoxyribose-5-phosphate aldolase through semi-rational design and overexpression of four enzymes in recombinant escherichia coli, namely methanol dehydrogenase, ethanol dehydrogenase, deoxyribose-5-phosphate aldolase, 1, 3-propylene glycol oxidoreductase or 1, 3-propylene glycol oxidoreductase isozyme, to construct unnatural 1, 3-propylene glycol from methanol, a formaldehyde-carbon compound, ethanol and acetaldehyde. The activity of the DERATMAS233D mutant screened by the invention is improved by 51% compared with that of a wild type enzyme; When the conversion from formaldehyde and ethanol to PDO by using escherichia coli, the yield of PDO is increased by 21.8%; when the formaldehyde and the acetaldehyde are converted into the PDO, the yield of the PDO is increased by 9.2%, the synthesis route of the PDO is greatly shortened, and the yield of the PDO is increased.