Significantly enhancing production of trans-4-hydroxy-l-proline by integrated system engineering in Escherichia coli.

ABSTRACT: Trans-4-hydroxy-l-proline is produced by trans-proline-4-hydroxylase with l-proline through glucose fermentation. Here, we designed a thorough "from A to Z" strategy to significantly improve trans-4-hydroxy-l-proline production. Through rare codon selected evolution, Escherichia coli M1 produced 18.2 g L^-1 l-proline. Metabolically engineered M6 with the deletion of putA, proP, putP, and aceA, and proB mutation focused carbon flux to l-proline and released its feedback inhibition. It produced 15.7 g L^-1 trans-4-hydroxy-l-proline with 10 g L^-1 l-proline retained. Furthermore, a tunable circuit based on quorum sensing attenuated l-proline hydroxylation flux, resulting in 43.2 g L^-1

SUBMITTER: Long M 

PROVIDER: S-EPMC7244267 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature