L-sugars, which are one large group of rare sugars, often hold enormous potential for the applications in the pharmaceutical industry. For example, several L-sugars can be used to produce L-nucleoside analogues, which showed increased antiviral activity, better metabolic stability, and more favorable toxicological profiles. Several (bio)chemical methods have been applied to synthesize L-sugars; however, the yields are extremely low with those methods. 

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 and constructed a recombination pathway based on DHAP-dependent aldolases and phosphorylase in Corynebacterium glutamicum to produce L-sugars. The research showed that some fructose 1,6-diphosphate aldolases (FruA) and tagatose 1,6-diphosphate (TagA) aldolases lost their strict stereoselectivity when using L-glyceraldehyde, and produced not only synthesized L-sorbose but also high proportion of L-psicose. Among the aldolases tested, TagA from Bacillus licheniformis (BGatY) showed highest enzyme activity to L-glyceraldehyde. Then, some recombinant pathways based on FruA or TagA and fructose-1-phosphatase (YqaB) were constructed in C. glutamicum, a gram-positive bacterium with GRAS status, to produce L-sorbose/L-psicose from glucose and L-glyceraldehyde. Intracellular DHAP and L-glyceraldehyde metabolic pathways were further engineered to increase product yield. Finally, fed-batch culture of the engineered strain produced 3.5 g/L L-sorbose and 2.3 g/L L-psicose with a yield of 0.61 g/g L-glyceraldehyde. This strategy could also be applied to synthesize other L-sugars efficiently.  

This work was supported by National High Technology Research and Development Program of china (No. 2013AA102105), Science and Technology Projects of Tianjin (No. 13ZCZDSY05600). The paper entitled “Biosynthesis of L-Sorbose and L-Psicose Based on C-C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain” has been published in the journal of Applied and Environmental Microbiology. Ph.D. YANG Jiangang is the first author of this paper.   

The strategy to produce L-sorbose/psicose by using microbial fermentation（Image by Prof. SUN Yuanxia’s group）