早熟假单胞菌 PMA22 产生 Safracin，这是一类具有强效广谱抗菌和抗肿瘤活性的化合物。 safracin 的生物合成基因簇 (BGC sac) 由 11 个 ORF 组成，这些 ORF 组织在两个不同的操纵子（sacABCDEFGHK 和 sacIJ）中，由 Pa 和 Pi 启动子控制。在 BGC 囊附近，我们找到了一个编码 LysR 家族推定全局调节因子的基因，注释为 MexT，最初被描述为假单胞菌中 MexEF-OprN 多药外排泵的转录激活因子。通过体外和体内实验，我们证明了双重调节系统 MexT-MexS 分别作为激活剂和阻遏剂参与 BGC 囊表达。 PMA22 的 MexEF-OprN 转运系统也受 MexT 控制，在 safracin 的代谢中发挥着重要作用。 PMA22 中 mexEF-oprN 的过度表达导致 safracin 的产量提高四倍。这些结果说明多效性调控系统对于优化定制次级代谢产物的生产至关重要，不仅通过与 BGC 启动子的直接相互作用，而且还通过控制其运输。

Pseudomonas poae PMA22 produces safracins, a family of compounds with potent broad-spectrum anti-bacterial and anti-tumor activities. The safracins' biosynthetic gene cluster (BGC sac) consists of 11 ORFs organized in two divergent operons (sacABCDEFGHK and sacIJ) that are controlled by Pa and Pi promoters. Contiguous to the BGC sac, we have located a gene that encodes a putative global regulator of the LysR family annotated as MexT that was originally described as a transcriptional activator of the MexEF-OprN multidrug efflux pump in Pseudomonas. Through both in vitro and in vivo experiments, we have demonstrated the involvement of the dual regulatory system MexT-MexS on the BGC sac expression acting as an activator and a repressor, respectively. The MexEF-OprN transport system of PMA22, also controlled by MexT, was shown to play a fundamental role in the metabolism of safracin. The overexpression of mexEF-oprN in PMA22 resulted in fourfold higher production levels of safracin. These results illustrate how a pleiotropic regulatory system can be critical to optimizing the production of tailored secondary metabolites, not only through direct interaction with the BGC promoters, but also by controlling their transport.