Homologous expression of lysA encoding diaminopimelic acid (DAP) decarboxylase reveals increased antibiotic production in Streptomyces clavuligerus

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Otur Ç., Kurt Kızıldoğan A.

BRAZILIAN JOURNAL OF MICROBIOLOGY, vol.51, no.2, pp.547-556, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 51 Issue: 2
  • Publication Date: 2020
  • Doi Number: 10.1007/s42770-019-00202-2
  • Journal Name: BRAZILIAN JOURNAL OF MICROBIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.547-556
  • Keywords: Streptomyces clavuligerus, lysA, Overexpression, Cephamycin C, Clavulanic acid, Tunicamycin, LYSINE EPSILON-AMINOTRANSFERASE, CEPHAMYCIN-C, CLAVULANIC ACID, HETEROLOGOUS EXPRESSION, ESCHERICHIA-COLI, BIOSYNTHESIS, TUNICAMYCIN, GENES, CCAR, CLUSTER
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

lysA gene encoding meso-diaminopimelic acid (DAP) decarboxylase enzyme that catalyzes l-lysine biosynthesis in the aspartate pathway in Streptomyces clavuligerus was overexpressed, and its effects on cephamycin C (CephC), clavulanic acid (CA), and tunicamycin productions were investigated. Multicopy expression of lysA gene under the control of glpF promoter (glpFp) in S. clavuligerus pCOlysA led to higher expression levels ranging from 2- to 6-fold increase at both lysA gene and CephC biosynthetic gene cluster at T-36 and T-48 of TSBG fermentation. These results accorded well with CephC production. Thus, 1.86- and 3.14-fold higher volumetric as well as 1.26- and 1.71-fold increased specific CephC yields were recorded in S. clavuligerus pCOlysA in comparison with the wild-type and its control strain, respectively, at 48th h. Increasing the expression of lysA provided 4.3 times more tunicamycin yields in the recombinant strain. These findings suggested that lysA overexpression in S. clavuligerus made the strain more productive for CephC and tunicamycin. The results also supported the presence of complex interactions among antibiotic biosynthesis pathways in S. clavuligerus.