Global Regulator AdpA_1075 Regulates Morphological Differentiation and Ansamitocin Production in Actinosynnema pretiosum subsp. auranticum

Actinosynnema pretiosum is a well-known producer of maytansinoid antibiotic ansamitocin P-3 (AP-3). Growth of A. pretiosum in submerged culture was characterized by the formation of complex mycelial particles strongly affecting AP-3 production. However, the genetic determinants involved in mycelial morphology are poorly understood in this genus. Herein a continuum of morphological types of a morphologically stable variant was observed during submerged cultures. Expression analysis revealed that the ssgA_6663 and ftsZ_5883 genes are involved in mycelial aggregation and entanglement. Combing morphology observation and morphology engineering, ssgA_6663 was identified to be responsible for the mycelial intertwining during liquid culture. However, down-regulation of ssgA_6663 transcription was caused by inactivation of adpA_1075, gene coding for an AdpA-like protein. Additionally, the overexpression of adpA_1075 led to an 85% increase in AP-3 production. Electrophoretic mobility shift assays (EMSA) revealed that AdpA_1075 may bind the promoter regions of asm28 gene in asm gene cluster as well as the promoter regions of ssgA_6663. These results confirm that adpA_1075 plays a positive role in AP-3 biosynthesis and morphological differentiation.