Glucose-1-phosphate thymidylyltransferase promotes the production of 3-O-α-mycarosylerythronolide B in Streptomyces coelicolor

被引:0
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作者
Gao, Hong [1 ]
Langer, Swen [2 ]
Larson, Tony [2 ]
Gregory, Matthew A. [3 ]
Smith, Margaret C.M. [1 ]
机构
[1] Department of Biology, University of York, Heslington, York, North Yorkshire,YO10 5DD, United Kingdom
[2] Bioscience Technology Facility, Department of Biology, University of York, Heslington, York, North Yorkshire,YO10 5DD, United Kingdom
[3] Isomerase Therapeutics, Newnham Building, Chesterford Research Park, Little Chesterford, Saffron Walden, Cambridge, Cambridgeshire,CB10 1XL, United Kingdom
基金
英国生物技术与生命科学研究理事会;
关键词
Biosynthesis;
D O I
10.1093/jambio/lxae291
中图分类号
学科分类号
摘要
Aims: The main objective of this study was to produce erythronolide B (EB) and 3-O-α-mycarosylerythronolide B (MEB) in Streptomyces coelicolor and enhance the MEB production by expressing the glucose-1-phosphate thymidylyltransferase (RfbA). Methods and results: We expressed eryF and eryB genes (eryBII, eryBIII, eryBIV, eryBV, eryBVI, and eryBVII) to produce EB and MEB. The expression was confirmed by quantitative real-time polymerase chain reaction. Furthermore, the MEB’s production was improved by more than 100-fold by expressing an enzyme, RfbA, which is absent from the erythromycin gene cluster, to promote the biosynthesis of TDP-L-mycarose. We discuss the feasibility of alternative Streptomyces species for erythromycin production based on the presence or absence of RfbA. Conclusions: The RbfA enzyme from Saccharopolyspora erythraea was expressed in S. coelicolor M1152 along with the MEB biosynthesis pathway, resulting in a large increase in MEB production (>100-fold). © The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International. All rights reserved.
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