This invention belongs to the field of
synthetic biology and microbial
engineering, and discloses a chemical-biological method for preparing the isopentenyl
bibenzyl compound 2-isopentenyl-3,3',4',5-tetrahydroxybibenzyl (NPB-1575) which has anti-
ischemic stroke activity. The specific disclosed method includes: (1) chemically synthesizing the substrate dihydropiperidine; (2) constructing an engineered
Escherichia coli strain based on the isopentenyl utilization pathway, co-expressing hydroxyethylthiazol
kinase, isopentenyl phosphokinase,
isopentenyl pyrophosphate isomerase and specific isopentenyl
transferase, and efficiently synthesizing the isopentenyl donor; (3) using this strain to catalyze dihydropiperidine in whole cells, the yield in a 200L fermenter can reach 2.54g / L, which is nearly 40 times higher than the existing method; (4) obtaining NPB-1575 with a purity >98.5% by macroporous adsorption resin and normal /
reversed phase chromatography and recrystallization. This method uses readily available raw materials, involves simple steps, is
environmentally friendly, and yields high purity, laying the foundation for the development of NPB-1575 as a new
drug for
ischemic stroke and showing significant application potential.