The Phormidolide Biosynthetic Gene Cluster: A trans-AT PKS Pathway Encoding a Toxic Macrocyclic Polyketide

被引：29
|
作者：
Bertin, Matthew J. [1 ]
Vulpanovici, Alexandra [2 ]
Monroe, Emily A. [3 ]
Korobeynikov, Anton [4 ]
Sherman, David H. [5 ]
Gerwick, Lena [1 ]
Gerwick, William H. [6 ]
机构：
[1] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, 9500 Gilman Dr,MC 0212, La Jolla, CA 92093 USA
[2] Oregon State Univ, Dept Biochem & Biophys, Agr & Life Sci 2011, 2750 SW Campus Way, Corvallis, OR 97331 USA
[3] William Paterson Univ, Dept Biol, 300 Pompton Rd, Wayne, NJ 07470 USA
[4] St Petersburg State Univ, Dept Stat Modeling, Ctr Algorithm Biotechnol, Univ Skiy 28, St Petersburg 198504, Russia
[5] Univ Michigan, Inst Life Sci, Dept Microbiol & Immunol, Dept Chem,Life Sci Inst 4008,Dept Med Chem, 210 Washtenaw Ave, Ann Arbor, MI 48109 USA
[6] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, 9500 Gilman Dr,MC 0212, La Jolla, CA 92093 USA
来源：
CHEMBIOCHEM | 2016年 / 17卷 / 02期
基金：
俄罗斯科学基金会;
关键词：
biosynthesis; macrolactones; phormidolide; polyketide synthase; trans-AT; NATURAL-PRODUCT; PEPTIDE SYNTHETASE; BACTERIAL SYMBIONT; SYNTHASE; DOMAIN; ORGANIZATION; STEREOCHEMISTRY; IDENTIFICATION; CYANOBACTERIA; MACROLACTONE;
D O I：
10.1002/cbic.201500467
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Phormidolide is a polyketide produced by a cultured filamentous marine cyanobacterium and incorporates a 16-membered macrolactone. Its complex structure is recognizably derived from a polyketide synthase pathway, but possesses unique and intriguing structural features that prompted interest in investigating its biosynthetic origin. Stable isotope incorporation experiments confirmed the polyketide nature of this compound. We further characterized the phormidolide gene cluster (phm) through genome sequencing followed by bioinformatic analysis. Two discrete trans-type acyltransferase (trans-AT) ORFs along with KS-AT adaptor regions (ATd) within the polyketide synthase (PKS) megasynthases, suggest that the phormidolide gene cluster is a trans-AT PKS. Insights gained from analysis of the mode of acetate incorporation and ensuing keto reduction prompted our reevaluation of the stereochemistry of phormidolide hydroxy groups located along the linear polyketide chain.
引用
收藏
页码：164 / 173
页数：10
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