ketosynthase domain
Recently Published Documents


TOTAL DOCUMENTS

17
(FIVE YEARS 0)

H-INDEX

10
(FIVE YEARS 0)

2020 ◽  
Vol 15 (9) ◽  
pp. 2422-2432 ◽  
Author(s):  
Maja Klaus ◽  
Lynn Buyachuihan ◽  
Martin Grininger

2020 ◽  
Vol 295 (33) ◽  
pp. 11602-11612 ◽  
Author(s):  
Choong-Soo Yun ◽  
Kazuki Nishimoto ◽  
Takayuki Motoyama ◽  
Takeshi Shimizu ◽  
Tomoya Hino ◽  
...  

Many microbial secondary metabolites are produced by multienzyme complexes comprising nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). The ketosynthase (KS) domains of polyketide synthase normally catalyze the decarboxylative Claisen condensation of acyl and malonyl blocks to extend the polyketide chain. However, the terminal KS domain in tenuazonic acid synthetase 1 (TAS1) from the fungus Pyricularia oryzae conducts substrate cyclization. Here, we report on the unique features of the KS domain in TAS1. We observed that this domain is monomeric, not dimeric as is typical for KSs. Analysis of a 1.68-Å resolution crystal structure suggests that the substrate cyclization is triggered via proton abstraction from the active methylene moiety in the substrate by a catalytic His-322 residue. Additionally, we show that TAS1 KS promiscuously accepts aminoacyl substrates and that this promiscuity can be increased by a single amino acid substitution in the substrate-binding pocket of the enzyme. These findings provide insight into a KS domain that accepts the amino acid–containing substrate in an NRPS–PKS hybrid enzyme and provide hints to the substrate cyclization mechanism performed by the KS domain in the biosynthesis of the mycotoxin tenuazonic acid.


2020 ◽  
Author(s):  
Maja Klaus ◽  
Lynn Buyachuihan ◽  
Martin Grininger

AbstractModular polyketide synthases (PKSs) produce complex, bioactive secondary metabolites in assembly line-like multistep reactions. Longstanding efforts to produce novel, biologically active compounds by recombining intact modules to new modular PKSs have mostly resulted in poorly active chimeras and decreased product yields. Recent findings demonstrate that the low efficiencies of modular chimeric PKSs also result from rate limitations in the transfer of the growing polyketide chain across the non-cognate module:module interface and further processing of the non-native polyketide substrate by the ketosynthase (KS) domain. In this study, we aim at disclosing and understanding the low efficiency of chimeric modular PKSs and at establishing guidelines for modular PKSs engineering. To do so, we work with a bimodular PKS testbed and systematically vary substrate specificity, substrate identity, and domain:domain interfaces of the KS involved reactions. We observe that KS domains employed in our chimeric bimodular PKSs are bottlenecks with regards to both substrate specificity as well as interaction with the ACP. Overall, our systematic study can explain in quantitative terms why early oversimplified engineering strategies based on the plain shuffling of modules mostly failed and why more recent approaches show improved success rates. We moreover identify two mutations of the KS domain that significantly increased turnover rates in chimeric systems and interpret this finding in mechanistic detail.


2018 ◽  
Vol 130 (35) ◽  
pp. 11393-11397
Author(s):  
Srividhya Sundaram ◽  
Hak Joong Kim ◽  
Ruth Bauer ◽  
Tawatchai Thongkongkaew ◽  
Daniel Heine ◽  
...  
Keyword(s):  

2018 ◽  
Vol 57 (35) ◽  
pp. 11223-11227 ◽  
Author(s):  
Srividhya Sundaram ◽  
Hak Joong Kim ◽  
Ruth Bauer ◽  
Tawatchai Thongkongkaew ◽  
Daniel Heine ◽  
...  
Keyword(s):  

Biochemistry ◽  
2016 ◽  
Vol 55 (32) ◽  
pp. 4476-4484 ◽  
Author(s):  
Thomas Robbins ◽  
Joshuah Kapilivsky ◽  
David E. Cane ◽  
Chaitan Khosla

2016 ◽  
Vol 52 (54) ◽  
pp. 8373-8376 ◽  
Author(s):  
Annabel C. Murphy ◽  
Hui Hong ◽  
Steve Vance ◽  
R. William Broadhurst ◽  
Peter F. Leadlay

An in vitro model system based on a ketosynthase domain of the erythromycin polyketide synthase was used to probe the apparent substrate tolerance of ketosynthase domains of the mycolactone polyketide synthase.


2015 ◽  
Vol 11 (12) ◽  
pp. 949-951 ◽  
Author(s):  
Srividhya Sundaram ◽  
Daniel Heine ◽  
Christian Hertweck

2013 ◽  
Vol 4 (8) ◽  
pp. 3212 ◽  
Author(s):  
Christoph Kohlhaas ◽  
Matthew Jenner ◽  
Annette Kampa ◽  
Geoff S. Briggs ◽  
José P. Afonso ◽  
...  

2011 ◽  
Vol 64 (9) ◽  
pp. 617-620 ◽  
Author(s):  
Hisayuki Komaki ◽  
Tomohiko Tamura ◽  
Ken-ichiro Suzuki
Keyword(s):  
Type I ◽  

Sign in / Sign up

Export Citation Format

Share Document