Mahenthiralingam Eshwar, Song Lijiang, Sass Andrea, White Judith, Wilmot Ceri, Marchbank Angela, Boaisha Othman, Paine James, Knight David, Challis Gregory L
Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University, Wales, UK.
Chem Biol. 2011 May 27;18(5):665-77. doi: 10.1016/j.chembiol.2011.01.020.
Gram-negative Burkholderia cepacia complex (Bcc) isolates were screened for antimicrobial activity against cystic fibrosis microbial pathogens, and the ability of B. ambifaria to inhibit B. multivorans was identified. The activity was mapped to a cluster of cryptic, quorum-sensing-regulated modular polyketide synthase (PKS) genes. Enacyloxin IIa and its stereoisomer designated iso-enacyloxin IIa were identified as metabolic products of the gene cluster, which encoded an unusual hybrid modular PKS consisting of multiple proteins with sequence similarity to cis-acyltransferase (cis-AT) PKSs and a single protein with sequence similarity to trans-AT PKSs. The discovery of the potent activity of enacyloxins against drug-resistant bacteria and the gene cluster that directs their production provides an opportunity for engineered biosynthesis of innovative enacyloxin derivatives and highlights the potential of Bcc bacteria as an underexploited resource for antibiotic discovery.
对革兰氏阴性洋葱伯克霍尔德菌复合体（Bcc）分离株进行了针对囊性纤维化微生物病原体的抗菌活性筛选，并确定了阿氏伯克霍尔德菌抑制多食伯克霍尔德菌的能力。该活性被定位到一组隐秘的、群体感应调节的模块化聚酮合酶（PKS）基因簇。鉴定出伊纳西洛辛IIa及其立体异构体异伊纳西洛辛IIa是该基因簇的代谢产物，该基因簇编码一种不寻常的杂合模块化PKS，由多个与顺式酰基转移酶（cis-AT）PKS具有序列相似性的蛋白质和一个与反式AT PKS具有序列相似性的单一蛋白质组成。伊纳西洛辛对耐药细菌的强大活性以及指导其产生的基因簇的发现为工程化生物合成创新的伊纳西洛辛衍生物提供了机会，并突出了Bcc细菌作为一种未充分利用的抗生素发现资源的潜力。
