Using chicken to lay eggs and enzyme catalysis to expand the capacity of lincomamide compound library

Explanation of the salicylic acid part in the biosynthesis of paecilomycin - creation of lincomamide antibiotic compound library (http://pubs.rsc.org/en/content/articlehtml/2017/sc/c6sc04235j; doi: 10.1039/c6sc04235j) Highlights: 1) it was found that the salicylic acid in the structure of celestine was partially involved in the condensation reaction by ccb2 (acyl CoA ligase) and ccb1 (acyltransferase) were involved; 2) the heterologous expression and in vitro enzymatic reaction identified and characterized ccb2, Ccb1 improved the biosynthesis route of paecilomycin; 3) using the metabolic intermediates and benzoic acid derivatives in the biosynthesis process of lincomycin, the lincomycin compounds library was established with the catalysis of CCB series enzymes, and the active screening was carried out to obtain the high active compounds; Figure 1: Ideas of this article（ Please refer to the literature) Brief introduction: lincomycin, clindamycin, celesticetin and other compounds have good antibacterial activity and are important antibiotics for clinical use In this paper, the key steps in the later stage of penicillin biosynthesis were explained Through heterologous expression and in vitro enzyme catalysis experiments, the specificity of enzyme ccb2 and ccb1 was identified and characterized, and the role of salicylic acid in the synthesis of penicillin catalyzed by enzyme ccb2 and ccb1 was confirmed, and the biosynthesis roadmap of penicillin was drawn completely (see Figure 2) Subsequently, the researchers synthesized a series of benzoic acid derivatives, combined with a series of lincomamide compounds obtained in the early stage, under the catalysis of enzyme CB2 and CB1, the lincomamide compounds library was expanded (see Figure 1) In the subsequent screening experiments, lincomamide compounds with better antibacterial activity were obtained (see Fig 3) The above experiments show that it is possible to construct a large number of compounds with a small amount of natural products based on the relevant mechanism of biosynthesis without chemical synthesis Figure 2: the terminal biosynthetic steps of lincomycin and celesticetin (from chem SCI) Fig 3: disc dispersion bioassay with gram-positive strain K rhizophila Structural differences between the components include o-metrology at the sacharide mobility (black), the side chain at the mini acid mobility (red), and orientation of the sulfur (blue); diameter of the investment zones is stated in the upper leftcorner Chem SCI) series of previous recommendations on biosynthesis: 1 Biosynthesis of sterol like natural products in unusual ways; 2 Magic hand, revealing hidden compounds; 3 Biosynthesis of anisomycin, a pyrrolidine protein synthesis inhibitor: new gene integration and hidden biosynthesis steps Note: due to the limited ability of the author, please leave a message if there are any questionable points above, and we will contact you actively! Reprint please indicate: CBG information, Tao Xiaohua Welcome to the "CBG information" WeChat official account and QQ group: 498263368 (click join to join CBG- [biosynthesis]: https://jq.qq.com/ _wv=1027&k=49bs909, enter the secret number: Name + unit or research direction)