Home
Resources
Publications
Characterization of the Tautomycin Biosynthetic Gene Cluster From Streptomyces Spiroverticillatus Unveiling New Insights Into Dialkylmaleic Anhydride and Polyketide Biosynthesis

Characterization of the Tautomycin Biosynthetic Gene Cluster From Streptomyces Spiroverticillatus Unveiling New Insights Into Dialkylmaleic Anhydride and Polyketide Biosynthesis

Wenli Li, Jianhua Ju, Scott R Rajski, Hiroyuki Osada, Ben Shen

J Biol Chem. 2008 Oct 17;283(42):28607-17.

PMID: 18708355

Abstract:

Tautomycin (TTM) is a highly potent and specific protein phosphatase inhibitor isolated from Streptomyces spiroverticillatus. The biological activity of TTM makes it an important lead for drug discovery, whereas its spiroketal-containing polyketide chain and rare dialkylmaleic anhydride moiety draw attention to novel biosynthetic chemistries responsible for its production. To elucidate the biosynthetic machinery associated with these novel molecular features, the ttm biosynthetic gene cluster from S. spiroverticillatus was isolated and characterized, and its involvement in TTM biosynthesis was confirmed by gene inactivation and complementation experiments. The ttm cluster was localized to a 86-kb DNA region, consisting of 20 open reading frames that encode three modular type I polyketide synthases (TtmHIJ), one type II thioesterase (TtmT), five proteins for methoxymalonyl-S-acyl carrier protein biosynthesis (Ttm-ABCDE), eight proteins for dialkylmaleic anhydride biosynthesis and regulation (TtmKLMNOPRS), as well as two additional regulatory proteins (TtmF and TtmQ) and one tailoring enzyme (TtmG). A model for TTM biosynthesis is proposed based on functional assignments from sequence analysis, which agrees well with previous feeding experiments, and has been further supported by in vivo gene inactivation experiments. These findings set the stage to fully investigate TTM biosynthesis and to biosynthetically engineer new TTM analogs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP109946352	Tautomycin from Streptomyces spiroverticillatus		109946-35-2	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: