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

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 Sacc...

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Main Authors: Li Cao, Yangchun Liu, Lin Sun, Zirong Zhu, Danlu Yang, Ziyuan Xia, Duo Jin, Zirui Dai, Jie Rang, Liqiu Xia
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-12-01
Series:Synthetic and Systems Biotechnology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405805X24000966
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author Li Cao
Yangchun Liu
Lin Sun
Zirong Zhu
Danlu Yang
Ziyuan Xia
Duo Jin
Zirui Dai
Jie Rang
Liqiu Xia
author_facet Li Cao
Yangchun Liu
Lin Sun
Zirong Zhu
Danlu Yang
Ziyuan Xia
Duo Jin
Zirui Dai
Jie Rang
Liqiu Xia
author_sort Li Cao
collection DOAJ
description 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.
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spelling doaj-art-badb534a20b64b99966491f12db4edd22025-08-20T01:56:23ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2024-12-019480981910.1016/j.synbio.2024.06.007Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosaLi Cao0Yangchun Liu1Lin Sun2Zirong Zhu3Danlu Yang4Ziyuan Xia5Duo Jin6Zirui Dai7Jie Rang8Liqiu Xia9Hunan 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, ChinaHunan 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, ChinaHunan 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, ChinaHunan 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, ChinaHunan 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, ChinaHunan 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, ChinaHunan 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, ChinaHunan 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, ChinaHunan 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, ChinaCorresponding author.; 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, ChinaTriacylglycerol (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.http://www.sciencedirect.com/science/article/pii/S2405805X24000966Saccharopolyspora spinosaSpinosadTriacylglycerolLipaseAcyl-CoAs
spellingShingle Li Cao
Yangchun Liu
Lin Sun
Zirong Zhu
Danlu Yang
Ziyuan Xia
Duo Jin
Zirui Dai
Jie Rang
Liqiu Xia
Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa
Synthetic and Systems Biotechnology
Saccharopolyspora spinosa
Spinosad
Triacylglycerol
Lipase
Acyl-CoAs
title Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa
title_full Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa
title_fullStr Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa
title_full_unstemmed Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa
title_short Enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in Saccharopolyspora spinosa
title_sort enhanced triacylglycerol metabolism contributes to the efficient biosynthesis of spinosad in saccharopolyspora spinosa
topic Saccharopolyspora spinosa
Spinosad
Triacylglycerol
Lipase
Acyl-CoAs
url http://www.sciencedirect.com/science/article/pii/S2405805X24000966
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