ArticleMicrobial biotechnology2026
Branched-Chain Amino Acids Mediate the Regulation of SACE_Lrp on the Aminotransferase IlvE Involved in Erythromycin Biosynthesis in Saccharopolyspora erythraea.
Article in Microbial biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Erythromycin is a broad-spectrum polyketide antibiotic which can be obtained mainly through biosynthesis. The catabolic pathway of branched-chain amino acids (BCAAs) significantly influences the biosynthesis of erythromycin. However, the regulatory mechanisms controlling the BCAA catabolic pathway in actinobacteria remain poorly understood, particularly in key industrial antibiotics-producing actinobacteria. This study investigates the role of BCAA aminotransferase IlvE controlled by an Lrp-family regulator SACE_Lrp in erythromycin biosynthesis and enhances erythromycin yield through a coupled strategy involving regulator manipulation and BCAA supplementation. In this work, we demonstrated that SACE_Lrp directly controlled the expression of ilvE in the presence of BCAAs, and BCAA supplementation promoted the binding of SACE_Lrp to the ilvE promoter in vivo and in vitro. BCAAs addition results in a higher increase of ilvE transcription and erythromycin production in ΔSACE_Lrp than in Saccharopolyspora erythraea A226. Gene disruption of ilvE in S. erythraea A226 resulted in a 63% decrease in erythromycin production, while overexpression of ilvE in A226 and Streptomyces coelicolor M145 enhanced erythromycin and actinorhodin production by 74% and 58%, respectively. Furthermore, overexpression of ilvE in the industrial strain S. erythraea WB (WB/pIB-ilvE) and WBΔSACE_Lrp/5387-5386 (WBΔSACE_Lrp/5387-5386-ilvE) led to 28%, and 48% increase in erythromycin production, respectively, compared to WB. Additionally, supplementation with 30 mM valine in WBΔSACE_Lrp/5387-5386-ilvE cultures further increased total erythromycin production by 71%. This work expands the understanding of the role of SACE_Lrp in the molecular regulation of antibiotic biosynthesis in S. erythraea and provides an efficient approach for boosting erythromycin yield.
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