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[P02-290]Metabolic Engineering of Bacillus subtilis for Heterologous Itaconic Acid Production

○Ngangom Pravina Devi1, Guhan Jayaraman1 (1. IIT Madras (India))
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Keywords:

Metabolic engineering,Bacillus subtilis,Itaconic acid

Bacillus subtilis has historically served as a model organism in microbiology and molecular genetics, owing to its well-characterized physiology, genetic tractability, and established GRAS status. Apart from its conventional role as a model Gram-positive bacterium, B. subtilis is increasingly being recognized as a promising microbial chassis for metabolic engineering and sustainable biomanufacturing. It’s high growth rate, tolerance to extreme environmental conditions such as pH, temp. etc. and high protein secretion capacity establishes it as an attractive alternative to traditional hosts such as E. coli and S. cerevisiae. Recent advances in synthetic biology have expanded our capacity to rationally reprogram the metabolism of B. subtilis for the production of industrially important biomolecules including enzymes, organic acids etc. By employing strategic pathway engineering and flux optimisation, it is now feasible to improve precursor availability, balance redox cofactors, and redirect carbon flux towards target molecules while eliminating generation of by-products. Advancing computational tools and genome-scale models have further enhanced the potential of B. subtilis as a reliable and versatile cell factory.In this work we are developing a strategic approach for the engineering of B. subtilis as a robust microbial platform for the production of itaconic acid (IA), a valuable bio-based chemical with applications in bioplastics, superabsorbent materials, and other industrial sectors. While Aspergillus terreus has traditionally been utilized for IA production, its limitations - such as slow growth rates, pathogenicity, sporulation, and complex fermentation conditions - highlight the need for alternative microbial systems. Bacillus subtilis offers distinct advantages, including rapid growth, Generally Recognised As Safe (GRAS) status, ease of genetic manipulation, and a well-established fermentation framework. Our work aims to introduce and optimize the heterologous biosynthesis pathways necessary for IA production in Bacillus subtilis. In addition, metabolic flux will be optimised to reduce by-product formation and enhance the availability of precursors. Through a combination of strain engineering and fermentation optimization approaches, we seek to develop an efficient Bacillus subtilis strain capable of producing itaconic acid at commercially viable levels. This work has the potential to transform IA production, providing a sustainable alternative to fungal systems and contributing to the broader movement toward biobased chemical manufacturing. By thoughtfully combining rational strain engineering and dynamic metabolic controls, B. subtilis has the potential to support biomanufacturing processes that are both carbon-neutral and resource-efficient, thereby laying a solid foundation for a greener, more sustainable bioeconomy.

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