Metabolic engineering is a technologic platform for industrial strain improvement and aims not only at modifying microbial metabolic fluxes, but also improving the physiological performance of industrial microbes. Microbes will meet multiple stresses in industrial processes. Consequently, elicited gene responses might result in a decrease in overall cell fitness and the efficiency of biotransformation. Thus, it is crucial to develop robust and productive microbial strains that can be integrated into industrial-scale bioprocesses. In this review, we focus on the progress of these novel methods and strategies for engineering stress-tolerance phenotypes referring to rational metabolic engineering and inverse metabolic engineering in recent years. In addition, we also address problems existing in this area and future research needs of microbial physiological functionality engineering.
Bacteria ; genetics ; metabolism ; Bacterial Physiological Phenomena ; Biotechnology ; methods ; Fungi ; genetics ; metabolism ; physiology ; Industrial Microbiology ; methods ; Metabolic Engineering ; methods ; Metabolic Networks and Pathways ; Stress, Physiological

BACKGROUNDIn the TARGET I randomized controlled trial, the novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent FIREHAWK proved non-inferior to the everolimus-eluting stent in nine-month in-stent late loss in single de novo coronary lesions. This study was aimed at evaluating clinical safety and effectiveness of FIREHAWK in a moderately complex population (including patients with small vessels, long lesions and multi-vessels), and at validating the ability of the SYNTAX score (SS) to predict clinical outcomes in patients treated with this latest generation drug-eluting stent.

METHODSTARGET II was a prospective, multicenter, single-arm study with primary outcome of 12-month target lesion failure (TLF), including cardiac death, target vessel myocardial infarction (TV-MI) and ischemia-driven target lesion revascularization (TLR). Stent thrombosis was defined according to the Academic Research Consortium (ARC) definition. Patients were grouped by tertiles of SS (≤6, >6 to ≤12, and >12). All patients were exclusively treated with the FIREHAWK stent and were followed up at 1, 6, and 12 months, and annually thereafter up to five years.

RESULTSA total of 730 patients were included in this registry study. The 12-month incidence of TLF was 4.4% and the incidence of TLF components were, cardiac death 0.5%, TV-MI 3.2%, and TLR 2.2%. One definite/probable stent thrombosis was observed at 12-month follow-up. Mean SS was 10.87±6.87. Patients in the SS >12 tertile had significantly higher TLF (P = 0.02) and TLR (P < 0.01) rates than those in lower SS groups. In COX proportional-hazards regression analyses, TLF incidence was strongly related to lesion length (long lesion vs. non-long lesion patients; HR 3.416, 95% CI, 1.622-7.195), but unrelated to diabetic, small vessel, and multivessel subgroups.

CONCLUSIONSThe low TLF incidence in this study indicates that FIREHAWK is safe and effective in the treatment of moderately complex coronary disease. SS is also able to predict adverse clinical outcomes in FIREHAWK treated patients.

Adolescent ; Adult ; Aged ; Biocompatible Materials ; chemistry ; Cardiovascular Agents ; therapeutic use ; Coronary Stenosis ; drug therapy ; therapy ; Coronary Vessels ; pathology ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Polymers ; Proportional Hazards Models ; Sirolimus ; therapeutic use ; Young Adult