I. Biosynthesis of Avermectins A. Incorporation of Labeled Precursors B. Biosynthetically Blocked Mutants and Characteristics of Each Step in Avermectin Biosynthetic Pathway 1. aveA {aveAI and aveAIh step for polyketide synthase) 2. aveB (step for glycosylation) 3. aveC (step for C22~23-dehydration) 4. aveD (step for C5 O-methylation) 5. aveE (step for furan ring formation at C6 to C8a) 6. aveF...

The polyene macrolide antibiotic filipin is widely used as a probe for cholesterol in biological membranes. The filipin biosynthetic pathway of Streptomyces avermitilis contains two position-specific hydroxylases, C26-specific CYP105P1 and C1'-specific CYP105D6. In this study, we describe the three X-ray crystal structures of CYP105P1: the ligand-free wild-type (WT-free), 4-phenylimidazole-boun...

Analysis of the gene cluster from Streptomyces avermitilis that governs the biosynthesis of the polyketide anthelmintic avermectin revealed that it contains four large ORFs encoding giant multifunctional polypeptides of the avermectin polyketide synthase (AVES 1, AVES 2, AVES 3, and AVES 4). These clustered polyketide synthase genes responsible for avermectin biosynthesis together encode 12 hom...

In our previous studies, AveI was identified as a negative regulator for avermectin biosynthesis in Streptomyces avermitilis NRRL8165, and the aveI-null mutant of NRRL8165 could produce at least 10-fold more avermectin B1a than its wild-type strain. In order to explore the regulatory mechanism by which aveI affects avermectin biosynthesis, in this study, we performed a global comparative gene e...