Industrial biotechnology lecture: Harnessing Enzymatic Power for Bioenergy and Therapeutics
Lecture by Dr. Debasis Das.
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Gustav Wieds Vej 10C, 8000 Aarhus C, Building 3130, Room 303
Organizer
Abstract: Enzymes are Nature’s favorite tools for performing chemical reactions at enormous speed. We aim to understand and utilize some of Nature’s most challenging and unknown enzymes for bioenergy and therapeutic applications.
Biosynthetically produced 1-alkenes hold immense value as sustainable alternatives to fossil fuels and find widespread applications in polymer, lubricant, and detergent industries. UndB is the only known membrane enzyme capable of converting fatty acids to 1-alkenes. However, despite diverse applications, UndB remains poorly understood since its discovery nearly a decade ago. We present here insights into the molecular basis of UndB catalysis and the mechanism of UndB reaction at the membrane interface. We unravel UndB as a diiron-enzyme that utilizes a conserved histidine cluster at the active site. We decipher the dependency of UndB activity on molecular oxygen and electrons and identify the most efficient redox partners of UndB. We elucidate the catalytic intricacies of UndB and establish it as the most efficient decarboxylase in producing industrially valuable medium-chain 1-alkenes. Further, we engineer UndB for and develop a novel whole-cell biocatalyst for highly efficient conversion (up to 95%) of naturally abundant free fatty acids to 1-alkenes.
Biofilm-associated microbial infections are serious threats to human health as biofilm is a major line of microbial defense and a prime strategy for chronic diseases. Conventional anti-biofilm methods fail to treat preformed biofilms due to poor penetrance and biocompatibility. We present here the striking ability of an orphan cow rumen microbial enzyme to rapidly disperse the mature biofilms of several clinical isolates of Klebsiella pneumoniae, a critical threat pathogen. This enzyme exerts unusually high stability and activity, dispersing mature biofilms at a low micromolar concentration under physiological conditions. This enzyme readily performs antibiotic and immune system potentiation against the poorly responsive biofilm-associated pathogen and synergizes with antibiotic treatment of biofilm-associated K. pneumoniae wound infection in mice, resulting in rapid wound healing. Our study unveils the massive potential of cow rumen microbial enzymes for the dispersion of mature biofilms, which could revolutionize the treatment landscape for antibiotic-resistant biofilm-associated pathogens.
References:
- Iqbal, T., Murugan, S. Das, D.* Science Advances, 2024, 10, eadl2492.
- Ramakrishnan, R.; Nair, A. V.; Parmar, K.; Rajmani, R. S.; Chakravortty, D.* and Das, D.* (Under revision)
- Murugan, S.; Iqbal, T. and Das, D.* Protein Science, 2024, 33, e4893.
- Iqbal, T.; Murugan, S.; Rajendran, K.; Sidhu, J. S. and Das, D.* ACS Catalysis, 2023, 13, 23, 15516. [Front Cover]
- Iqbal, T. and Das, D.* Biochemistry, 2022, 61, 10, 909–921 [Front Cover]
- Iqbal, T.; Chakraborty, S.; Murugan S. and Das, D.* Chem. Asian J., 2022 e202200105. [Front Cover]
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Debasis Das
Assistant Professor
Department of Inorganic and Physical Chemistry
Indian Institute of Science, Bangalore
Contact Number: 8317865764
e-Mail: debasisdas@iisc.ac.in
Homepage: sites.google.com/view/ddlaboratory/home
Debasis received his Ph.D. in Chemistry (Chemical Biology) from the University of Michigan, Ann Arbor, USA, in 2014. Followed by his postdoctoral work at MIT, USA, Debasis joined the Indian Institute of Science, Bangalore, India as an assistant professor in 2019. His research area is interdisciplinary in nature, which has flavors of both Chemistry and Biology. His group focuses on the mechanistic understanding of various metalloenzymes and their applications. Employing various tools of chemistry, biochemistry, molecular biology, and microbiology, his group is exploring the function, kinetics, mechanism, and reaction intermediates of several poorly understood enzymes. The long-term goal of the work is to engineer and utilize these enzymes in green energy applications and therapeutics. He is an EMBO Global Investigator and recipient of the Excellence of Research Award 2013 given by the University of Michigan, Excellence of Research Award 2024 and Excellence in Teaching Award 2024 given by IISc Bangalore, India and Graeme Hanson AsBIC Early Career Award 2024 by Asian Biological Inorganic Chemistry Society.
Representative Publications:
- Iqbal, T.; Murugan, S. and Das, D.* A Chimeric Membrane Enzyme and an Engineered Whole-cell Biocatalyst for Efficient 1-Alkene Production, Science Advances, 2024, 10, eadl2492. [This article is featured by IISc Press The Times Of India, The Hindu, Deccan Herald, The New India Express, Energy World, LatestLY, BioEnergy Times, Neo Science Hub, Greenleaf, Udayavani), USA (EurekAlert!, Phys.org, MSN, Scienmag, Bioengineer.org), UK (AZoCleantech - The Online Clean Technology Community), Australia (Mirage), Germany (Germanic)].
- Murugan, S.; Iqbal, T. and Das, D.* Functional Production and Biochemical Investigation of an Integral Membrane Enzyme for Olefin Biosynthesis. Protein Science, 2024, 33, e4893
- Iqbal, T.; Murugan, S.; Rajendran, K.; Sidhu, J. S. and Das, D.* Unraveling the Conversion of Fatty Acids into Terminal Alkenes by an Integral Membrane Enzyme, UndB. ACS Catalysis, 2023, 13, 23, 15516. [This article is featured on the Front Cover of the journal, featured by IISc News, and the KERNEL magazine]
- Sidhu, J. S.; Rajendran, K.; Mathew, A. B.; Iqbal, T. ; Saini, D. K. and Das, D.* Acetylcholine structure-based small activatable fluorogenic probe for specific detection of acetylcholinesterase, Analytical Chemistry, 2023, 95, 19, 7594–7602 [This article is featured by IISc Press, PhysOrg, and several leading newspapers: Times of India, Hindustan Times, Deccan Herald, India Today, Today Headline, The Week Magazine, MedIndia, Mirage News, Latest LY, Alzforum etc.]
- Iqbal, T. and Das, D.* Biochemical Investigation of Membrane-Bound Cytochrome b5 and Catalytic Domain of Cytochrome b5 Reductase from Arabidopsis Thaliana, Biochemistry, 2022, 61, 10, 909–921. [Featured as the Front Cover of the journal]