The Oxytetracycline Producer Streptomyces lydicamycinicus bja295 and Its Genomic Context

Oxytetracycline (OTC) production is classically attributed to Streptomyces rimosus, and the distribution of its biosynthetic gene cluster (BGC) across the genus is poorly understood. We describe Streptomyces lydicamycinicus bja295 as an OTC producer, the first demonstrated for this species, and the distribution of the BGC across the genus. OTC was identified by mass spectrometry, and the titre reached 200 mg/L on ISP2, the most productive medium tested. A maximum-likelihood tree of 138 single-copy core proteins places the strain within S. lydicamycinicus as sister to its type strain at 99.36% ANI; the genome is a linear chromosome of 8,072,839 bp (71.2% GC). Its intact locus comprises 24 genes and lacks an ortholog of oxyO, a gene of the canonical S. rimosus cluster of long-debated function; since the strain produces OTC, oxyO is not required for the trait in this background. Of 13,198 Streptomyces genomes screened, 137 carry the BGC (1.04%): every other assembly of S. lydicamycinicus; the single assemblies of S. albofaciens, S. viridifaciens and S. aureofaciens; and subclades within S. rimosus, S. varsoviensis, S. platensis and S. halstedii. In non-carriers, the syntenic site holds unrelated 15-27 kb blocks or nothing, while otrA and otrB persist without the biosynthetic core, marking where the cluster once stood rather than a capacity to produce. Carriage is thus structured by lineage rather than scattered across the genus, and carriage, structural integrity and demonstrated production are three separate statements about a genome.