title: The SARP Family Regulator Txn9 and Two-Component Response Regulator Txn11 are Key Activators for Trioxacarcin Biosynthesis in Streptomyces bottropensis.
abstract: Trioxacarcin A is a polyoxygenated, structurally complex antibiotic produced by Streptomyces spp., which possesses high anti-bacterial, anti-malaria, and anti-tumor activities. The trioxacarcin biosynthetic pathway involves type II polyketide synthases (PKSs) with L-isoleucine as a unique starter unit, as well as many complex post-PKS tailoring enzymes and resistance and regulatory proteins. In this work, two regulatory genes, txn9 coding for a Streptomyces antibiotic regulatory protein family regulator and txn11 for a two-component response regulator, were revealed to be absolutely required for trioxacarcin production by individually inactivating all the six annotated regulatory genes in the txn cluster. Complementation assay suggested that these two activators do not have a regulatory cascade relationship. Moreover, transcriptional analysis showed that they activate 15 of the 28 txn operons, indicating that a complicated regulatory network is involved in the trioxacarcin production. Information gained from this study may be useful for improving the production of the highly potent trioxacarcin A.
authors.affiliation: School of Perfume and Aroma Technology, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai, 201418, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Yang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Qi
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Hou
authors.forename: Hai-Xue
authors.initials: HX
authors.lastname: Pan
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis*; D000890:Anti-Infective Agents / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D005816:Genetic Complementation Test; D005810:Multigene Family; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D000617:Aminoglycosides; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D015534:Trans-Activators; C033790:trioxacarcin