Affiliations 

  • 1 School of Marine and Environmental Sciences, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia; Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM MOSTI, Malaysia
  • 2 Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM MOSTI, Malaysia
  • 3 School of Biological Sciences, Universiti Sains Malaysia, 11800 Pulau Pinang, Malaysia
  • 4 Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM MOSTI, Malaysia; School of Fundamental Science, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia
  • 5 Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM MOSTI, Malaysia; School of Biological Sciences, Universiti Sains Malaysia, 11800 Pulau Pinang, Malaysia; Centre for Chemical Biology, Universiti Sains Malaysia, 11900 Bayan Lepas, Pulau Pinang, Malaysia
  • 6 School of Marine and Environmental Sciences, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia; Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM MOSTI, Malaysia; Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia. Electronic address: kesaven@umt.edu.my
Enzyme Microb Technol, 2017 Mar;98:1-8.
PMID: 28110659 DOI: 10.1016/j.enzmictec.2016.11.011

Abstract

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] copolymer is noted for its high biocompatibility, which makes it an excellent candidate for biopharmaceutical applications. The wild-type Cupriavidus sp. USMAA1020 strain is able to synthesize P(3HB-co-4HB) copolymers with different 4HB monomer compositions (up to 70mol%) in shaken flask cultures. Combinations of 4HB carbon precursors consisting of 1,6-hexanediol and γ-butyrolactone were applied for the production of P(3HB-co-4HB) with different 4HB molar fraction. A sharp increase in 4HB monomer composition was attained by introducing additional copies of PHA synthase gene (phaC), responsible for P(3HB-co-4HB) polymerization. The phaC of Cupriavidus sp. USMAA1020 and Cupriavidus sp. USMAA2-4 were cloned and heterologously introduced into host, wild-type Cupriavidus sp. USMAA1020. The gene dosage treatment resulted in the accumulation of 93mol% 4HB by the transformant strains when grown in similar conditions as the wild-type USMAA1020. The PHA synthase activities for both transformants were almost two-fold higher than the wild-type. The ability of the transformants to produce copolymers with high 4HB monomer composition was also tested in large scale production system using 5L and 30L bioreactors with a constant oxygen mass transfer rate. The 4HB monomer composition could be maintained at a range of 83-89mol%. The mechanical and thermal properties of copolymers improved with increasing 4HB monomer composition. The copolymers produced could be tailored for specific biopharmaceutical applications based on their properties.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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