UoB University Graduate School
The hunt for new antibiotics
Polyketides are bioactive natural products and some of the most important medicines; they are synthesized by bacteria, fungi and some plants and represent an important group of structurally diverse and clinically useful compounds which include antibiotics like erythromycin and tetracycline, anticancer drugs and immunosuppressants, as such understanding the biosynthetic pathways of the different polyketide compounds is essential for creating new families of bioactive compounds with potentially useful properties. Using mutasynthesis, mutagenesis and gene cloning, we investigate the possibility of creating new hybrid molecules through manipulating the biosynthetic genes of different polyketide systems; including Mupirocin, Thiomarinols and Aminocoumarins. Our results shows that SimL (an amide ligase in the Aminocoumarins pathway) has no effect on Mupirocin or Thiomarinol production, which makes it a strong candidate for creating hybrid compounds based on Mupirocin. Work is underway to further exploit Aminocoumarins in creation of new hybrids by introducing it to both P.fluorescens NCIMB10586 and P.alteromonas SANK73390. The outcome of these experiments will determine to what extent Aminocoumarins can be used to combine independent antibiotic biosynthetic pathways and consequently aid in developing a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA.
Yusra Alsammarraie
PhD
College of Life and Environmental Sciences
The hunt for new antibiotics
Polyketides are bioactive natural products and some of the most important medicines; they are synthesized by bacteria, fungi and some plants and represent an important group of structurally diverse and clinically useful compounds which include antibiotics like erythromycin and tetracycline, anticancer drugs and immunosuppressants, as such understanding the biosynthetic pathways of the different polyketide compounds is essential for creating new families of bioactive compounds with potentially useful properties. Using mutasynthesis, mutagenesis and gene cloning, we investigate the possibility of creating new hybrid molecules through manipulating the biosynthetic genes of different polyketide systems; including Mupirocin, Thiomarinols and Aminocoumarins. Our results shows that SimL (an amide ligase in the Aminocoumarins pathway) has no effect on Mupirocin or Thiomarinol production, which makes it a strong candidate for creating hybrid compounds based on Mupirocin. Work is underway to further exploit Aminocoumarins in creation of new hybrids by introducing it to both P.fluorescens NCIMB10586 and P.alteromonas SANK73390. The outcome of these experiments will determine to what extent Aminocoumarins can be used to combine independent antibiotic biosynthetic pathways and consequently aid in developing a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA.
Yusra Alsammarraie
PhD
College of Life and Environmental Sciences