Deoxysugars exhibit various significant biological activities and often play important roles in many crucial physiological reactions, particularly in the interaction of anti-cancer drugs with DNA.
2-deoxy-D-ribose 5-phosphate aldolase (DERA, EC 184.108.40.206) can catalyze reversible condensation between acetaldehyde and other non-phosphorylated aldehydes, and thus shows potential for use in de novo synthesis of many kinds of 2-deoxysugars. Despite the versatility of DERA, some obstacles limit its large-scale application in organic synthesis. DERA has a strong preference for phosphorylated substrates and is rapidly and irreversibly inactivated at high aldehyde concentrations.
The Laboratory of Functional Sugar and Natural Bioactive Products led by Dr. SUN Yuanxia at Tianjin Institute of Industrial Biotechnology (TIB), Chinese Academy of Sciences (CAS) designed a whole-cell transformation strategy based on 2-deoxy-D-ribose 5-phosphate aldolase to produce 2-deoxysugars. DERA from Klebsiella pneumoniae (KDERA) was mutated to improve its activity and substrate resistance towards non-phosphorylated polyhydroxy aldehydes.
Subsequently, a whole-cell transformation strategy using resting cells of recombinant E. coli strain was adopted to further increase its resistance to higher substrate concentrations. With further optimization of the transformation process, the BL21(pKDERA12) strain produced 2.14 M (287.06 g/L) 2-deoxy-D-ribose, with a yield of 0.71 mol/mol D-glyceraldehyde and average productivity of 0.13 mol/L.h (17.94 g/L.h).
This strategy was successfully applied to efficiently produce C5 and C6 2-deoxysugars from polyhydroxy aldehydes.
This work was supported by National High Technology Research and Development Program of china. The paper entitled “Biosynthesis of 2-deoxysugars using whole-cell catalyst expressing 2-deoxy-d -ribose 5-phosphate aldolase” has been published in the journal of Applied Microbiology and Biotechnolog. M.S. LI Jitao Ph.D. YANG Jiangang is the first co-author of this paper.
The synthesis of 2-deoxy-D-ribose (Image by Prof. SUN Yuanxia’s group)
Pro. Sun Yuanxia
Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences