Falzone Maria, Crespo Emmanuel, Jones Klarissa, Khan Gulaba, Korn Victoria L, Patel Amreen, Patel Mira, Patel Krishnaben, Perkins Carrie, Siddiqui Sana, Stenger Drew, Yu Eileen, Gelber Michael, Scheffler Robert, Nayda Vasyl, Ravin Ariela, Komal Ronica, Rudolf Jeffrey D, Shen Ben, Gullo Vincent, Demain Arnold L
Research Institute of Scientists Emeriti (RISE), Charles A. Dana Research Institute, Drew University, Madison, NJ, USA.
Department of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.
J Antibiot (Tokyo). 2017 Jul;70(7):828-831. doi: 10.1038/ja.2017.49. Epub 2017 May 3.
Streptomyces platensis MA7327 is a bacterium producing interesting antibiotics, which act by the novel mechanism of inhibiting fatty acid biosynthesis. The antibiotics produced by this actinomycete are platensimycin and platencin plus some minor related antibiotics. Platensimycin and platencin have activity against antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus; they also lack toxicity in animal models. Platensimycin also has activity against diabetes in a mouse model. We have been interested in studying the effects of primary metabolites on production of these antibiotics in our chemically defined production medium. In the present work, we tested 32 primary metabolites for their effect. They included 20 amino acids, 7 vitamins and 5 nucleic acid derivatives. Of these, only l-aspartic acid showed stimulation of antibiotic production. We conclude that the stimulatory effect of aspartic acid is due to its role as a precursor involved in the biosynthesis of aspartate-4-semialdehyde, which is the starting point for the biosynthesis of the 3-amino-2,4-dihydroxy benzoic acid portion of the platensimycin molecule.
普拉特链霉菌MA7327是一种能产生有趣抗生素的细菌,其作用机制是通过抑制脂肪酸生物合成这一新颖方式。这种放线菌产生的抗生素有扁平霉素和扁平菌素以及一些少量的相关抗生素。扁平霉素和扁平菌素对耐抗生素细菌如耐甲氧西林金黄色葡萄球菌和耐万古霉素肠球菌有活性;它们在动物模型中也没有毒性。在小鼠模型中,扁平霉素对糖尿病也有活性。我们一直对在化学成分明确的生产培养基中研究初级代谢产物对这些抗生素产量的影响感兴趣。在目前的工作中,我们测试了32种初级代谢产物的作用。它们包括20种氨基酸、7种维生素和5种核酸衍生物。其中,只有L-天冬氨酸显示出对抗生素生产的刺激作用。我们得出结论,天冬氨酸的刺激作用是由于它作为参与天冬氨酸-4-半醛生物合成的前体的作用,而天冬氨酸-4-半醛是扁平霉素分子中3-氨基-2,4-二羟基苯甲酸部分生物合成的起点。