Regulation of butanol biosynthesis in Clostridium acetobutylicum ATCC 824 under the influence of zinc supplementation and magnesium starvation.

Present study reports modulation in butanol biosynthesis in Clostridium acetobutylicum ATCC 824 under the influence of zinc supplementation or magnesium starvation either individually or in combination. An improvement in butanol titer from 11.83 g L-1 in control to 13.72 g L-1, 15.79 g L-1, and 19.18 g L-1 was achieved when organism was grown on magnesium starved, zinc supplemented and combined zinc supplemented-magnesium starved fermentation medium, respectively. The elevation in butanol biosynthesis was associated with raised glucose utilization, reduced ethanol production and early induction of solventogenesis. Change in these phenotypic traits of the organism may be attributed to multi-level modulation in central carbon metabolism e.g., upregulation of glycolytic pathway; upregulation in thiolase activity; key intermediate enzyme for biosynthesis of acids and solvent; upregulation in the activity of butyrylaldehyde dehydrogenase & butanol dehydrogenase, the enzymes responsible for butanol biosynthesis and downregulation in alcohol dehydrogenase, redirecting carbon flux from ethanol to butanol.

Nutrient modulation based process engineering strategy for improved butanol production from Clostridium acetobutylicum.

The present study demonstrates a process engineering strategy to achieve high butanol titer and productivity from wild type Clostridium acetobutylicum MTCC 11274. In the first step, two different media were optimized with the objectives of maximizing the biomass and butanol productivity, respectively. In the next step, attributes of these two media compositions were integrated to design a two-stage fed-batch process which resulted in maximal butanol productivity of 0.55 g L-1 h-1 with titer of 13.1 g L-1 . Further, two-stage fed-batch process along with combinatorial use of magnesium limitation and calcium supplementation resulted in the highest butanol titer and productivity of 16.5 g L-1 and 0.59 g L-1 h-1 , respectively. Finally, integration of the process with gas stripping and modulation of feeding duration resulted in a cumulative butanol titer of 54.3 g L-1 and productivity of 0.58 g L-1 h-1 . The strategy opens up possibility of developing a viable butanol bioprocess. © 2019 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2771, 2019.

Synchronized growth and neutral lipid accumulation in Chlorella sorokiniana FC6 IITG under continuous mode of operation.

Synchronized growth and neutral lipid accumulation with high lipid productivity under mixotrophic growth of the strain Chlorella sorokiniana FC6 IITG was achieved via manipulation of substrates feeding mode and supplementation of lipid elicitors in the growth medium. Screening and optimization of lipid elicitors resulted in lipid productivity of 110.59mgL(-1)day(-1) under the combined effect of lipid inducers sodium acetate and sodium chloride. Fed-batch cultivation of the strain in bioreactor with intermittent feeding of limiting nutrients and lipid inducer resulted in maximum biomass and lipid productivity of 2.08 and 0.97gL(-1)day(-1) respectively. Further, continuous production of biomass with concomitant lipid accumulation was demonstrated via continuous feeding of BG11 media supplemented with lipid inducers sodium acetate and sodium chloride. The improved biomass and lipid productivity in chemostat was found to be 2.81 and 1.27gL(-1)day(-1) respectively operated at a dilution rate of 0.54day(-1).

Chemoprevention of colorectal cancer.

Colorectal cancer is a major cause of mortality and treatment costs are considerable. Advocating lifestyle modification, faecal occult blood testing and surveillance colonoscopy in appropriate populations are already in practice. A developing concept is chemoprevention. Several models of carcinogenesis in colorectal cancer have been developed and there is an increasing database on the major molecular mechanisms involved in carcinogenesis mainly from preclinical experiments and phase I trials. There have been several large epidemiological and observational studies to evaluate possible protective effects of >200 agents. More recently, case-control and cohort studies and well-conceived, phase II/III clinical trials have been done or are under way to evaluate putative chemopreventive agents including established drugs like aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), 5-aminosalicylates and statins; more controversial drugs like cyclo-oxygenase-2 (COX-2) inhibitors, ursodeoxycholic acid; various vitamins and micronutrients including calcium, selenium, folic acid, and dietary fibre, fat and protein content. Despite promising outcome in preclinical studies, there is currently very limited data from well-controlled and appropriately powered clinical studies. The most promising agents currently are aspirin, traditional NSAIDs and COX-2 inhibitors. The recent reports of cardiovascular risks of the COX-2 inhibitors and some traditional NSAIDs have resulted in stagnation of the field. Pending the expected release of results from several phase III trials in the near future, chemoprevention for colorectal cancer can only be practically considered in the very-high-risk population like those with familial adenomatous polyposis and ulcerative colitis, in conjunction with surveillance colonoscopy. This article reviews the major models of colorectal carcinogenesis, the concept of chemoprevention with special reference to colorectal cancer and the current state of clinical literature and the future direction of colorectal cancer chemoprevention for both researcher and clinician alike.