SYNTHETIC BIOLOGY-GUIDED REPROGRAMMING OF MICROBIAL METABOLISM FOR ENHANCED PRODUCTION OF BIOACTIVE SECONDARY METABOLITES

Dr. Jyoti Vinod Dombe; Dr. Shambhavi Singh; Dr Neeraj Kumar Saha; Dr Bharat Agravat; Dr Manoj Kumar K; Dr Trupti Bajpai

Dr. Jyoti Vinod Dombe Associate professor, Samhita Siddhant department, Rajershi shahu Maharaj Ayurved college hospital and Research center. Buldhana
Dr. Shambhavi Singh Assistant Professor, Department: Microbiology, Government Medical College, Haldwani, HNB Uttarakhand Medical Education University
Dr Neeraj Kumar Saha Associate Professor, Microbiology Department, Birsa Institute of Medical Science and Research , Ranchi University
Dr Bharat Agravat Surgeon, Gujarat University
Dr Manoj Kumar K Post graduate, Department of Microbiology, Rajarajeswari medical college and hospital
Dr Trupti Bajpai Assistant professor, Department of Microbiology, Zydus Medical College Dahod Gujrat

Abstract

A combination of pathway engineering, host optimization, and controlled cultivation of microbial hosts is a powerful strategy for enhancing their production of high-value bioactive secondary metabolites using synthetic biology. In this work, the effects of designed pathway design, microbial chassis, cultivation media and growth-related parameters on the production of flavonoids and alkaloids were investigated. Comparative analysis revealed that screening of the designed flavonoids in an iterative fashion could significantly increase the production of pinocembrin, and the best-flavoured second round resulted in a mean concentration of 9.723 mg/L. The selection of microbial chassis also had a significant effect; as the MDS42 chassis with the design 2165 had the highest overall mean for pinocembrin production, the MG1655 chassis with the design 3382 had the best strain–design combination. Metabolite yield was strongly affected by the type of cultivation medium, with AIM providing significantly more than M9. In the case of metabolic optimization, significant and positive correlations were obtained between the production of induction biomass and pinocembrin and cinnamate concentrations, with biomass accounting for only a small proportion of the total production variation. Alkaloid pathway analysis showed that pathway products were redistributed in a pathway design-specific manner, with optimal production of tetrahydropapaveroline, reticuline and scoulerine achieved by different pathway configurations.