title: Identification and characterization of the biosynthetic gene cluster of polyoxypeptin A, a potent apoptosis inducer.
abstract: BACKGROUND
  Polyoxypeptin A was isolated from a culture broth of Streptomyces sp. MK498-98 F14, which has a potent apoptosis-inducing activity towards human pancreatic carcinoma AsPC-1 cells. Structurally, polyoxypeptin A is composed of a C₁₅ acyl side chain and a nineteen-membered cyclodepsipeptide core that consists of six unusual nonproteinogenic amino acid residues (N-hydroxyvaline, 3-hydroxy-3-methylproline, 5-hydroxypiperazic acid, N-hydroxyalanine, piperazic acid, and 3-hydroxyleucine) at high oxidation states.
  
  
  RESULTS
  A gene cluster containing 37 open reading frames (ORFs) has been sequenced and analyzed for the biosynthesis of polyoxypeptin A. We constructed 12 specific gene inactivation mutants, most of which abolished the production of polyoxypeptin A and only ΔplyM mutant accumulated a dehydroxylated analogue polyoxypeptin B. Based on bioinformatics analysis and genetic data, we proposed the biosynthetic pathway of polyoxypeptin A and biosynthetic models of six unusual amino acid building blocks and a PKS extender unit.
  
  
  CONCLUSIONS
  The identified gene cluster and proposed pathway for the biosynthesis of polyoxypeptin A will pave a way to understand the biosynthetic mechanism of the azinothricin family natural products and provide opportunities to apply combinatorial biosynthesis strategy to create more useful compounds.
authors: Yanhua
authors: Y
authors: Du
authors: Yemin
authors: Y
authors: Wang
authors: Tingting
authors: T
authors: Huang
authors: Meifeng
authors: M
authors: Tao
authors: Zixin
authors: Z
authors: Deng
authors: State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. linsj@sjtu.edu.cn.
authors: Shuangjun
authors: S
authors: Lin
mesh_terms: D053898:Biosynthetic Pathways / Q000235:genetics*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D055786:Gene Knockout Techniques; D008969:Molecular Sequence Data; D005810:Multigene Family; D010456:Peptides, Cyclic / Q000096:biosynthesis*; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial; D010456:Peptides, Cyclic; C121868:polyoxypeptin A