ABSTRACT
14- to 16-membered macrolide antibiotics (MA) are clinically important anti-infective drugs. With the rapid emergence of bacterial resistance, there is an urgent need to develop novel MA to counter drug-resistant bacteria. The targeted optimization of MA can be guided by analyzing the interaction between the MA and its ribosomal targets, and the desired MA derivatives can be obtained efficiently when combining with the rapidly developed metabolic engineering approaches. In the past 30 years, metabolic engineering approaches have shown great advantages in engineering the biosynthesis of MA to create new derivatives and to improve their production. These metabolic engineering approaches include modification of the structural domains of the polyketide synthase (PKS) and post-PKS modification enzymes as well as combinatorial biosynthesis. In addition, the R&D (including the evaluation of its antimicrobial activities and the optimization through metabolic engineering) of carrimycin, a new 16-membered macrolide drug, are described in details in this review.
Subject(s)
Anti-Bacterial Agents , Bacteria/genetics , Macrolides , Metabolic Engineering , Polyketide SynthasesABSTRACT
As highly active anti-retroviral therapy continues, large numbers of drug-resistant strains appeared in human immunodeficiency virus ( HIV) infectors, which always leads to a decline of treatment results or even a treatment failure.The genotypic resistance analysis technique of the bioinformatics is a powerful tool to forecast the HIV resistance and also determines the success or failure of antiviral therapy.This review will be focus on the advantages and disadvantages, influence factor of the genotype resistance prediction and improve measure of the primary HIV drug resistance genotype interpretation system, depending on the principle and characteristics of the genotypic drug resistance analysis as the breakthrough point, in order to provide guidance for reasonable application of different genotypes drug resistance analysis system in China.