AbstractHuperzine A (HupA) is for treating Alzheimer's disease(AD) which was mainly extracted from the Huperzia serrata(HS). Especially, (-)-HupA extracted from HS with high inhibitory activity of acetylcholinesterase are scarce and the chemical synthesis of (+)- HupA is high toxicity with low acetylcholinesterase inhibitory activity. In this work, Serratia marcescens HL1 was firstly found and isolated from HS, that was identified according to their morphological characteristics and nuclear 16SDNA sequences. It could biosynthesize HupA(BHA) of 32.976 ± 0.21 mg/L which was co-cultivated after with endophytic fungi Trichoderma harzianum NSW-V. Moreover, this bacteria with shorter fermentation time could form better purity and crystal structure with the same physicochemical properties compared to (-)-HupA isolated from HS(PHA) according to the results of NMR and molecular docking. Furthermore, this study explored new indications for HupA which indicated it could protect β-cells of pancreatic islets.