State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Gene. 2012 Nov 10;509(2):195-200. doi: 10.1016/j.gene.2012.08.030. Epub 2012 Aug 25.
Phoslactomycins (PLMs) are inhibitors of protein serine/threonine phosphatase 2A showing diverse and important antifungal, antibacterial and antitumor activity. PLMs are polyketide natural products and produced by several Streptomyces species. The PLMs biosynthetic gene clusters were identified from Streptomyces platensis SAM-0654 and localized in two separate genomic regions, consisting of 27 open reading frames that encode polyketide synthases (PKSs), enzymes for cyclohexanecarboxyl-CoA (CHC-CoA) and ethylmalonyl-CoA (Em-CoA) synthesis, enzymes for post-PKS modifications, proposed regulators, and putative resistance transporters. Bioinformatic analysis and inactivation experiment of regulatory genes suggest that PnR1 and PnR2 are two positive regulators of PLMs biosynthesis. Gene transcription analysis by reverse transcriptase PCR (RT-PCR) of the PLMs gene cluster demonstrated that PnR1 and PnR2 activate the transcription of the structural biosynthetic genes while PnR2 specially governs the transcription of pnR1 in a higher level.
磷霉素（PLMs）是蛋白丝氨酸/苏氨酸磷酸酶 2A 的抑制剂，具有多样且重要的抗真菌、抗菌和抗肿瘤活性。PLMs 是聚酮天然产物，由几种链霉菌属产生。PLMs 生物合成基因簇已从链霉菌属 platensis SAM-0654 中鉴定出来，并定位于两个独立的基因组区域，包含 27 个开放阅读框，编码聚酮合酶（PKSs）、环己烷羧酸-CoA（CHC-CoA）和乙基丙二酸-CoA（Em-CoA）合成酶、后 PKS 修饰酶、假定的调节剂和潜在的抗性转运蛋白。调控基因的生物信息学分析和失活实验表明，PnR1 和 PnR2 是 PLMs 生物合成的两个正调控因子。通过逆转录 PCR（RT-PCR）对 PLMs 基因簇的基因转录分析表明，PnR1 和 PnR2 激活结构生物合成基因的转录，而 PnR2 则在更高水平上专门调控 pnR1 的转录。
