Biochemistry of the Hydroxyprolines

Liu

Appl Microbiol Biotechnol

et al. 2018

Section: Discussionmentioning

confidence: 99%

Biochemical and genetic characterization of fungal proline hydroxylase in echinocandin biosynthesis

Liu

Appl Microbiol Biotechnol

et al. 2018

Section: Introductionmentioning

confidence: 99%

“…Hydroxyprolines (Hyps) are l-proline (l-Pro) derivatives hydroxylated at C3 or C4 with different enantioselectivities (1). Hyps have been widely used in fields such as biochemistry, food production, and cosmetics development (1). Hyps are also heavily involved in many secondary metabolic pathways for the biosynthesis of various drugs, such as chemotherapeutic actinomycin, antifungal echinocandin, antibiotic etamycin, and anti-inflammatory oxaceprol (2).…”

Section: Introductionmentioning

confidence: 99%

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

Long

Pan

et al. 2020

Sci. Adv.

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−1l-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−1trans-4-hydroxy-l-proline with 10 g L−1l-proline retained. Furthermore, a tunable circuit based on quorum sensing attenuated l-proline hydroxylation flux, resulting in 43.2 g L−1trans-4-hydroxy-l-proline with 4.3 g L−1l-proline retained. Finally, rationally designed l-proline hydroxylase gave 54.8 g L−1trans-4-hydroxy-l-proline in 60 hours almost without l-proline remaining—the highest production to date. The de novo engineering carbon flux through rare codon selected evolution, dynamic precursor modulation, and metabolic engineering provides a good technological platform for efficient hydroxyl amino acid synthesis.

“…Hydroxyproline is a specific amino acid constituent of collagen, and it has four isomers, namely Trans‐ 4‐hydroxy‐L‐proline (Hyp), trans ‐3‐L‐hydroxyproline, cis ‐4‐L‐hydroxyproline, and cis ‐3‐L‐hydroxyproline . Among them, Hyp is the most abundant of the components of collagen and helps to enhance the synthesis of procollagen .…”

Section: Introductionmentioning

confidence: 99%

Construction and optimization of trans‐4‐hydroxy‐L‐proline production recombinant E. coli strain taking the glycerol as carbon source

Wang

J of Chemical Tech & Biotech

Liu

et al. 2016

BACKGROUND: Trans-4-hydroxy-L-proline (Hyp) is a value-added amino acid that is an applicable chiral building block in some industries, such as the pharmaceutical, cosmetic and healthcare industries. Given that glycerol is a good carbon source for microbial fermentation and a large amount of glycerol is produced by the biodiesel industry, this study investigated a value-added Hyp fermentation from glycerol using an engineered Escherichia coli strain. RESULTS: By optimizing the proline-4-hydroxylase (P4H) gene codons and vectors, a constructed recombinant Escherichia coliBL21 strain successfully converted L-proline to Hyp. With a chemo-physical combination mutagenesis, a high Hyp production strain that can grow with glycerol as a sole carbon source, NA45 was isolated, yielding 1.24 g L −1 from 20 g L −1 glycerol at 12 h in a 30 mL/250 mL conical flask fermentation. With further systemic optimization of nutritional elements, the output was enhanced to 1.62 g L −1 . In a 5 L fermentator, the strain achieved a surprisingly high output of 25.4 g L −1 at 48 h in fed batch mode. CONCLUSION: A high Hyp production strain growing well on glycerol as carbon source was successfully engineered, which is a promising candidate for the industrial Hyp production.