Microbial Whole-Cell Biocatalysis for Phloretin Production from Naringenin

Area of Science:

• Biotechnology
• Microbial Engineering
• Metabolic Engineering

Background:

• Phloretin, a dihydrochalcone, has significant pharmaceutical and nutraceutical value.
• Traditional plant extraction methods for phloretin are inefficient.
• A microbial-based production system for phloretin is needed.

Purpose of the Study:

• To establish a bioconversion pathway for phloretin production from naringenin in Lactobacillus plantarum.
• To optimize the engineered pathway for increased phloretin yield.
• To demonstrate the feasibility of using L. plantarum as a host for flavonoid biosynthesis.

Main Methods:

• Screening of heterologous iron-sulfur cluster-containing enoate reductases.
• Coexpression of flavin reductases and formate dehydrogenases for cofactor regeneration.
• Promoter engineering, iron uptake gene overexpression, and iron concentration optimization.
• Structure-guided semirational design of enoate reductase.

Main Results:

• A novel biosynthetic route for phloretin production in L. plantarum was successfully established.
• Dual NADH-FAD cofactor regeneration system was implemented.
• Engineered L. plantarum achieved a phloretin titer of 70.53 mg/L.
• The D656R mutant of enoate reductase was identified, enhancing phloretin production.

Conclusions:

• Lactobacillus plantarum is a viable and promising host for phloretin biosynthesis.
• The developed bioconversion pathway significantly improves phloretin production efficiency.
• This study represents the first report of flavonoid biosynthesis in L. plantarum, opening avenues for producing phloretin derivatives.