Industrial Biotechnology

Five Groups at ICGEB New Delhi develop technologies for the production of clean energy from biological sources. The goal of the Microbial Engineering Group (Yazdani) is to develop cost-effective processes to produce second-generation biofuels; they isolate novel enzymes (cellulases, xylanases) with higher specificity towards cellulosic biomass, and engineer fungi with enzymes that can produce biofuels from this energy source. The Group uses metabolic engineering and synthetic biology approaches to produce high-density fuels and green chemicals. This includes developing novel yeast strains for microbial biorefineries to produce fuels and chemicals in a cost-effective manner. The Groups focus on scale-up studies for industrial use and advanced fuel and chemical production. Algal Biology is the focus of the Omics of Algae Group (Jutur), where research aims to understand the molecular changes within algal systems through an integrative multi-omics approach with well-defined functional pathways that will elucidate an effective strategy for converting light/carbon source to biomass, biofuels, and biorenewables (B3) for sustainable solutions. Findings provide important breakthroughs on the essential metabolism in these microalgae, which is required for the biotechnological improvement of next-generation biofuels/biorenewables. The Systems Biology for Biofuels Group (Srivastava) conducts quantitative metabolic analyses, including the development of genome-scale metabolic models of biotechnologically important microorganisms to improve biofuel and bioproduct yields and rates, and investigates marine cyanobacteria as factories to produce biofuel candidate molecules. The Metabolic Engineering Group (Kumar) works on a sustainable algal biofuels programme using synthetic biology and genome-editing tools, aiming to reduce carbon footprints by introducing Carbon Concentration Mechanisms (CCM) into marine algae and knocking out genes that limit the carbon capture efficiency of photosynthetic organisms via RNAi/CRISPR Cas9. The process to develop an alkane-producing algal system for “drop-in jetfuel” is well underway. The Group also works on enhancing artemisinin biosynthesis in the Artemisia annua plant through chloroplast engineering to produce a complete artemisinin drug in edible plants for coherent treatment of malaria.

Highlights 

A major achievement of Yazdani’s Group has been the scale-up of its enzyme technology to a pre-commercial 15,000 litre scale for use in lignocellulosic biomass hydrolysis. The Group identified a drug efflux mechanism of the hypercellulolytic fungus Penicillium funiculosum and developed strategies to block these efflux pumps to develop effective transformation tools for genome engineering. The genetic toolkits were also extended to the co-expression of multiple proteins of diverse physiological implications. The Group performed extensive proteomic studies to discover some of the key enzymes necessary for effective hydrolysis of pre-treated sugarcane bagasse (Biotechnology for Biofuels, 2021). In terms of conferring tolerance to inhibitors during the fermentation of cellulosic biomass hydrolysate, the Group identified a novel oxidoreductase YghA that conferred tolerance to furfural in ethanologenic E. coli.

The Yazdani Group also undertook extensive biophysical and structural studies of a crucial hydrocarbon biosynthetic enzyme, acyl ACP reductase, which revealed the marginal stability of the enzyme. Metabolomic profiling of Rhodosporidium toruloides by the Gaur Group revealed the diversion of the cytidinediphosphate-diacylglycerol and glycerol pathways towards de novo triacylglycerol synthesis. Carotenoid(s) extracted from red yeast showed antimalarial activity against P. falciparum, and the Ddi1 gene of P. falciparum was expressed and characterised in yeast in the context of inhibition by artemisinin. Sphingolipidomics of drug-resistant clinical isolates of Candida auris revealed distinct sphingolipid species signatures, compared with susceptible isolates.

The Metabolic Engineering Group has been involved in improving photosynthetic organisms using synthetic biology approaches and participated in consortia of the international plant science community to address epidemic and pandemic diseases, and to develop affordable drugs in edible plants for endemic and re-emerging diseases. The Group developed the bioremediation technology “Cultivation of microalgae on unhydrolysed waste molasses syrup using mass cultivation strategy for improved biodiesel”. In collaboration of Tata Steel Pvt Ltd., the Group has developed a genetically improved super algal strain that can thrive well in industrial exhaust (10% CO2).