Dr. Amit Kumar Yadav, Scientist `D’ – NER (Scientific Decision Unit), Department of Biotechnology
Dr. Amit Kumar Yadav, Scientist `D’ – NER (Scientific Decision Unit), Department of Biotechnology, at a session on Biofoundry and Biomanufacturing Initiative series,conducted by Department of Biotechnology (DBT), discussed the potential of enzyme biomanufacturing to revolutionize industrial processes through sustainable practices and the advancements in genetic engineering and metagenomic to stabilize and improve the efficiency of enzymes. He also emphasized the challenges in the high-cost production and scalability of enzyme biomanufacturing. Following are the key insights from his address.
Traditional manufacturing relies on non-renewable fossils which leads to a rise in greenhouse gases and requires huge facilities to operate at high temperatures and pressures. Also, traditional manufacturing runs on high capital expenditure and does not support sustainable innovation. In contrast, biomanufacturing utilizes renewable sources and requires fermenters operating at low temperatures and pressure. Transition from traditional manufacturing to biomanufacturing presents an opportunity to create a more sustainable industrial landscape by embracing renewable sources and innovative practices. It enables to mitigate environmental impacts while fostering economic growth in diverse sectors with cleaner, greener, and sustainable solutions. Enzymes Biomanufacturing offers advantages over traditional chemical processes. Enzymatic solutions are sustainable in nature. Enzymes typically operate under milder conditions of temperature and pressure, which minimizes energy consumption and reduces the environmental impact associated with traditional chemical processes. Additionally, enzyme-catalyzed reactions produce fewer toxic byproducts, contributing to lower ecological footprint.
Enzymes have high stereo selectivity, which yields stereo and region chemically defined reaction products. With the advancement in genetic engineering, the development of enzymes improved stability and activity under various conditions. This includes enhancing thermal stability and optimizing pH levels for specific chemical applications, which is crucial for industrial processes. Enzymes are used in many industries and employed in a wide range of sectors, spanning from food, pharmaceuticals, and textiles, to biofuels, etc. In the paper and pulp industry, enzymes like cellulase, and xylanase are used for improved bleaching and improvement in fiber properties. In the detergent industry, protease, lipase, and amylase are used to remove stains. In pharmaceuticals enzymes like nitrile hydrolase, ketoreductase, and carboxylase are increasingly being used to catalyze specific chemical reactions, which are not sustainable at present. In food processing, trypsin, amylase, and pectinase are being used to convert starch to glucose and high fructose corn syrups.
In biofuel, converting cellulose to glucose is further converted to ethanol for its subsequent uses. In terms of globalization and Indian perspective, the India’s enzyme bioeconomy is 3-4% of the global market size. However, the Indian market is poised for growth through increased production capabilities and expanding applications across multiple industries. According to the Indian Bioeconomy Report 2024, significant growth has been seen in various sectors, particularly the textile and food industries, which leverage enzymatic processes. The textile sector grew by 18% to achieve a market valuation of 8.2 billion. In the food sector, the bread and biscuit segment grew and reached 2.68 to 2.8 billion respectively.
The major gap areas that need to be addressed in enzyme biomanufacturing is the high cost of production, which is mainly attributed to expensive substrates and are used in the enzyme production. Low yields of enzymes obtained after fermentation require larger volumes of raw materials, thereby increasing the overall cost of enzymes. However, achieving high titers is essential to make the process economically viable. In downstream processes, purification, formulation ensures adherence to quality standards and regulatory requirements increases the cost. High cost often makes it dependent on imports. Most commercially available enzymes are derived from mesophilic organisms and they are stable only within a limited range of conditions.
Enzymes tend to lose activity quickly when exposed to extreme temperatures, pH levels, or solvent concentrations that encountered during industrial applications. The challenge is to maintain efficiency and stability under such conditions. Many enzymes require cofactors to function effectively, and these cofactors must be replenished continuously during reaction. This adds both cost and complexity to the production process of enzymes. Moreover, during the scalar process, transitioning from lab-scale to industrial-scale production is challenging. It becomes difficult to maintain consistent growth conditions and enzyme activity at a larger scale and this usually leads to variations in product yield and quality.
The robustness of microbial strains used in fermentation is critical as any instability will result in product loss. Advanced technologies and methods have accelerated the future commercial production of enzymes. Novel enzymes are accessible through numerous microbes that inhabit the biosphere, although only a few are cultivable through standard laboratory techniques. However, advances in metagenomic approaches have provided an alternative strategy to conventional microbe screening by preparing genomic library from environmental DNA and systematically screening such libraries for open reading frame that may encode novel enzymes.
The genomic sequencing programs have caused an explosion of information available from sequence databases, thus creates opportunities to explore or finding newer enzymes by database mining. Extremophiles are interesting source of enzymes with extreme stability under conditions regarded as incompatible with biological material. Methods for production of cost effective synthetic genes are also exist for rapid affordable screening of enzyme variant using high throughput screening tools. Methods for production of cost effective synthetic genes are available for rapid affordable screening of enzyme variant using high throughput screening tools. Targeted protein engineering techniques involving site-directed mutagenesis and directed evolution, are also being applied to improve the properties of enzymes. Artificial intelligence plays a significant role in predicting the structures of enzymes and their corresponding characteristics and functions and makes the design of artificial enzymes more accurate.
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