Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa  

作　　者：Li Cao Yangchun Liu Lin Sun Zirong Zhu Danlu Yang Ziyuan Xia Duo Jin Zirui Dai Jie Rang Liqiu Xia 

机构地区：[1]Hunan Provincial Key Laboratory for Microbial Molecular Biology,State Key Laboratory of Development Biology of Freshwater Fish,College of Life Science,Hunan Normal University,Changsha,Hunan,410081,China

出　　处：《Synthetic and Systems Biotechnology》2024年第4期809-819,共11页合成和系统生物技术(英文)

基　　金：supported by funding from the National Natural Science Foundation of China(31770106,32200062);the Natural Science Foundation of Hunan Province(2024JJ5258).

摘　　要：Triacylglycerol(TAG)is crucial for antibiotic biosynthesis derived from Streptomyces,as it serves as an important carbon source.In this study,the supplementation of exogenous TAG led to a 3.92-fold augmentation in spinosad production.The impact of exogenous TAG on the metabolic network of Saccharopolyspora spinosa were deeply analyzed through comparative proteomics.To optimize TAG metabolism and enhance spinosad biosynthesis,the lipase-encoding genes lip886 and lip385 were overexpressed or co-expressed.The results shown that the yield of spinosad was increased by 0.8-fold and 0.4-fold when lip886 and lip385 genes were overexpressed,respectively.Synergistic co-expression of these genes resulted in a 2.29-fold increase in the yield of spinosad.Remarkably,the combined overexpression of lip886 and lip385 in the presence of exogenous TAG elevated spinosad yields by 5.5-fold,led to a drastic increase in spinosad production from 0.036 g/L to 0.234 g/L.This study underscores the modification of intracellular concentrations of free fatty acids(FFAs),short-chain acyl-CoAs,ATP,and NADPH as mechanisms by which exogenous TAG modulates spinosad biosynthesis.Overall,the findings validate the enhancement of TAG catabolism as a beneficial strategy for optimizing spinosad production and provide foundational insights for engineering secondary metabolite biosynthesis pathways in another Streptomyces.

关 键 词：Saccharopolyspora spinosa SPINOSAD TRIACYLGLYCEROL LipaseAcyl-CoAs 

分 类 号：Q78[生物学—分子生物学]