Enhanced Production of 4-Hydroxyvalerate by Engineering the lva Operon in Pseudomonas putida KT2440

Abstract

Monomeric 4-hydroxyvalerate (4HV) is a versatile chemical used to produce various commodities and fine chemicals. Conventional productions of 4HV suffer from various shortcomings, including low yield, use of harsh conditions, catalysts, and organic solvents, need for chemical modification, and incomplete depolymerisation. Therefore, in the present study, we deleted the lvaAB gene from the lva operon in Pseudomonas putida KT2440 and overexpressed tesB under the control of the lva operon system in a levulinic acid (LA) and 4HV inducible expression system to produce 4HV from LA. The lvaAB deleted strain showed almost complete conversion of LA to 4HV, compared with 24% conversion in the wild type strain. In addition, under optimized culture conditions, the final engineered strain produced a maximum of 50 g/L of 4HV with 97% conversion from LA. The system presented here could be applied to produce high titers of 4-hydroxyvalerate in a cost-effective manner at a large scale from renewable cellulosic biomass.