title: Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes.
abstract: Antibiotic production in Streptomyces can often be increased by introducing heterologous genes into strains that contain an antibiotic biosynthesis gene cluster. A number of genes are known to be useful for this purpose. We chose three such genes and cloned them singly or in combination under the control of the strong constitutive ermE* promoter into a φ-derived integrating vector that can be transferred efficiently by conjugation from Escherichia coli to Streptomyces. The three genes are adpA, a global regulator from Streptomyces coelicolor, metK, encoding S-adenosylmethionine synthetase from S. coelicolor, and, VHbS, hemoglobin from Vitreoscilla. The substitutions with GC in VHbS was intended to convert codons from lower usage to higher, yet causing no change to the encoded amino acid. Plasmids containing either one of these genes or genes in various combinations were introduced into Streptomyces sp. FR-008, which produces the macrolide antibiotic FR-008-III (also known as candicidin D). The largest increase in FR-008-III production was achieved by the plasmid containing all three genes. This plasmid also increased avermectin production in Streptomyces avermitilis, and is likely to be generally useful for improving antibiotic production in Streptomyces.
authors: State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China.
authors: Tao
authors: T
authors: Wang
authors: Linquan
authors: L
authors: Bai
authors: Dongqing
authors: D
authors: Zhu
authors: Xuan
authors: X
authors: Lei
authors: Guang
authors: G
authors: Liu
authors: Zixin
authors: Z
authors: Deng
authors: Delin
authors: D
authors: You
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D015870:Gene Expression; D005798:Genes, Bacterial; D005818:Genetic Engineering; D018942:Macrolides / Q000378:metabolism*; D008716:Methionine Adenosyltransferase / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D054793:Truncated Hemoglobins / Q000235:genetics / Q000378:metabolism; D020589:Vitreoscilla / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D018942:Macrolides; D015534:Trans-Activators; D054793:Truncated Hemoglobins; C082613:hemoglobin protein, Vitreoscilla; D008716:Methionine Adenosyltransferase